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The dataset generation failed because of a cast error
Error code: DatasetGenerationCastError
Exception: DatasetGenerationCastError
Message: An error occurred while generating the dataset
All the data files must have the same columns, but at some point there are 3 new columns ({'IUPAC Name', 'PubChem CID', 'Standardized SMILES'}) and 1 missing columns ({'IUPAC name'}).
This happened while the csv dataset builder was generating data using
zip://NMRBank_data_with_SMILES_156621_in_225809.csv::/tmp/hf-datasets-cache/medium/datasets/99996093384811-config-parquet-and-info-sweetssweets-NMRBank-cd81239d/hub/datasets--sweetssweets--NMRBank/snapshots/d9b8309cb1b27e0c2268007bfae0dd6d891d2aaf/NMRBank/NMRBank_data_with_SMILES_156621_in_225809.zip
Please either edit the data files to have matching columns, or separate them into different configurations (see docs at https://hf.co/docs/hub/datasets-manual-configuration#multiple-configurations)
Traceback: Traceback (most recent call last):
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1871, in _prepare_split_single
writer.write_table(table)
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/arrow_writer.py", line 623, in write_table
pa_table = table_cast(pa_table, self._schema)
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/table.py", line 2293, in table_cast
return cast_table_to_schema(table, schema)
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/table.py", line 2241, in cast_table_to_schema
raise CastError(
datasets.table.CastError: Couldn't cast
PMC accession number (PMCID): string
Paragraph: string
IUPAC Name: string
SMILES: string
1H NMR text: string
13C NMR text: string
1H NMR conditions: string
1H NMR chemical shifts: string
13C NMR conditions: string
13C NMR chemical shifts: string
Confidence in data given by large models: double
PMID: int64
Article Citation: string
Journal Name: string
Article publication time: double
License: string
LastUpdated (YYYY-MM-DD HH:MM:SS): string
Retracted: string
Standardized SMILES: string
PubChem CID: double
-- schema metadata --
pandas: '{"index_columns": [{"kind": "range", "name": null, "start": 0, "' + 2925
to
{'PMC accession number (PMCID)': Value(dtype='string', id=None), 'Paragraph': Value(dtype='string', id=None), 'IUPAC name': Value(dtype='string', id=None), 'SMILES': Value(dtype='string', id=None), '1H NMR text': Value(dtype='string', id=None), '13C NMR text': Value(dtype='string', id=None), '1H NMR conditions': Value(dtype='string', id=None), '1H NMR chemical shifts': Value(dtype='string', id=None), '13C NMR conditions': Value(dtype='string', id=None), '13C NMR chemical shifts': Value(dtype='string', id=None), 'Confidence in data given by large models': Value(dtype='float64', id=None), 'PMID': Value(dtype='int64', id=None), 'Article Citation': Value(dtype='string', id=None), 'Journal Name': Value(dtype='string', id=None), 'Article publication time': Value(dtype='float64', id=None), 'License': Value(dtype='string', id=None), 'LastUpdated (YYYY-MM-DD HH:MM:SS)': Value(dtype='string', id=None), 'Retracted': Value(dtype='string', id=None)}
because column names don't match
During handling of the above exception, another exception occurred:
Traceback (most recent call last):
File "/src/services/worker/src/worker/job_runners/config/parquet_and_info.py", line 1438, in compute_config_parquet_and_info_response
parquet_operations = convert_to_parquet(builder)
File "/src/services/worker/src/worker/job_runners/config/parquet_and_info.py", line 1050, in convert_to_parquet
builder.download_and_prepare(
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 925, in download_and_prepare
self._download_and_prepare(
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1001, in _download_and_prepare
self._prepare_split(split_generator, **prepare_split_kwargs)
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1742, in _prepare_split
for job_id, done, content in self._prepare_split_single(
File "/src/services/worker/.venv/lib/python3.9/site-packages/datasets/builder.py", line 1873, in _prepare_split_single
raise DatasetGenerationCastError.from_cast_error(
datasets.exceptions.DatasetGenerationCastError: An error occurred while generating the dataset
All the data files must have the same columns, but at some point there are 3 new columns ({'IUPAC Name', 'PubChem CID', 'Standardized SMILES'}) and 1 missing columns ({'IUPAC name'}).
This happened while the csv dataset builder was generating data using
zip://NMRBank_data_with_SMILES_156621_in_225809.csv::/tmp/hf-datasets-cache/medium/datasets/99996093384811-config-parquet-and-info-sweetssweets-NMRBank-cd81239d/hub/datasets--sweetssweets--NMRBank/snapshots/d9b8309cb1b27e0c2268007bfae0dd6d891d2aaf/NMRBank/NMRBank_data_with_SMILES_156621_in_225809.zip
Please either edit the data files to have matching columns, or separate them into different configurations (see docs at https://hf.co/docs/hub/datasets-manual-configuration#multiple-configurations)Need help to make the dataset viewer work? Make sure to review how to configure the dataset viewer, and open a discussion for direct support.
PMC accession number (PMCID)
string | Paragraph
string | IUPAC name
string | SMILES
string | 1H NMR text
string | 13C NMR text
string | 1H NMR conditions
string | 1H NMR chemical shifts
string | 13C NMR conditions
string | 13C NMR chemical shifts
string | Confidence in data given by large models
float64 | PMID
int64 | Article Citation
string | Journal Name
string | Article publication time
float64 | License
string | LastUpdated (YYYY-MM-DD HH:MM:SS)
string | Retracted
string |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
PMC1073692
|
4-Amino-1-tert-butyl-3-phenylpyrazolo[3,4-d] pyrimidines (PP2 and hydroxy-PP) were synthesized according to Hanefeld et al.[32]. Benzyl bromide was used to protect the hydroxyl group for the hydroxy-PP synthesis. Hydrogenation (10% palladium on carbon) resulted in benzyl deprotection to yield hydroxy-PP. 4-Amino-1-tert-butyl-3-phenylpyrazolo[3,4-d] pyrimidines (PP2 and hydroxy-PP) were synthesized according to Hanefeld et al.[32]. Benzyl bromide was used to protect the hydroxyl group for the hydroxy-PP synthesis. Hydrogenation (10% palladium on carbon) resulted in benzyl deprotection to yield hydroxy-PP. Hydroxy-PP: Colorless powder; 1H NMR (400 MHz, DMSO-d6) δ 9.69 (brs), 8.22 (1H, s), 7.33 (1H, dd, J = 7.5, 7.5 Hz), 7.05 (2H, m), 6.86 (1H, dd, J = 7.5, 2 Hz), 5.74 (s), 1.73 (9H, s). 13C NMR (100 MHz, DMSO-d6) δ 158.1 (s), 157.8 (s), 154.6 (d), 153.8 (s), 141.7 (s), 134.5 (s), 130.2 (d), 118.9 (d), 115.6 (d), 115.0 (d), 98.5 (s), 59.6 (s), 28.7 (q). HR-EIMS calculated for C15H17N5O 283.1433 found 283.1434.
|
hydroxy-PP
| null |
1H NMR (400 MHz, DMSO-d6) δ 9.69 (brs), 8.22 (1H, s), 7.33 (1H, dd, J = 7.5, 7.5 Hz), 7.05 (2H, m), 6.86 (1H, dd, J = 7.5, 2 Hz), 5.74 (s), 1.73 (9H, s)
|
13C NMR (100 MHz, DMSO-d6) δ 158.1 (s), 157.8 (s), 154.6 (d), 153.8 (s), 141.7 (s), 134.5 (s), 130.2 (d), 118.9 (d), 115.6 (d), 115.0 (d), 98.5 (s), 59.6 (s), 28.7 (q)
|
400 MHz, DMSO-d6
|
9.69 (brs), 8.22 (1H, s), 7.33 (1H, dd, J = 7.5, 7.5 Hz), 7.05 (2H, m), 6.86 (1H, dd, J = 7.5, 2 Hz), 5.74 (s), 1.73 (9H, s)
|
100 MHz, DMSO-d6
|
158.1, 157.8, 154.6, 153.8, 141.7, 134.5, 130.2, 118.9, 115.6, 115.0, 98.5, 59.6, 28.7
| 0.480605
| 15,799,708
|
PLoS Biol. 2005 May 5; 3(5):e128
|
PLoS Biol
| 2,005
|
CC BY
|
2021-01-05 08:21:21
|
no
|
PMC1262691
|
(1R, αR)-1, (1R, αS)-1, (1S, αR)-1, and (1S, αS)-1 (Figure 2) were prepared from the condensation of R-(+)- or S-(-)-α-methylbenzyl isocyanate ([α]20 D = +10° or -10°) with 1 equivalent of R-(+)- or S-(-)-1, 1'-bi-2-naphthol ([α]20 D = +34° or -34°) in the presence of a catalytic amount of pyridine in CH2Cl2 at 25°C for 24 h (80–95 % yield). All products were purified by liquid chromatography or medium pressure liquid chromatography (silica gel, hexane-ethyl acetate) and characterized by 1H and 13C NMR spectra and high resolution mass spectra. (1R, αR)-1, (1R, αS)-1, (1S, αR)-1, and (1S, αS)-1: 1H NMR (CDCl3, 300 MHz) δ/ppm 1.02 (d, J = 6.6 Hz, 3H, CH(Ph)CH3), 4.48 (quintet, J = 7 Hz, 1H, CH(Ph)CH3), 5.27 (d, J = 8.1 Hz, 1H, NH), 7.07–8.06 (m, 17H, aromatic H); 13C NMR (CDCl3, 75.4 MHz) δ/ppm 21.88 (CH3), 50.36 (CH(Ph)CH3), 122.45, 123.51, 125.43, 125.69, 126.08, 126.48, 126.60, 127.10, 127.24, 127.91, 128.18, 128.37, 128.53, 129.40, 131.40, 133.30, 133.41, 142.98, and 147.20 (aromatic Cs), 153.91 (C = O); High resolution mass spectra: Found: 433.1674; C29H23NO3 requires 433.1678. [α]25 D = +40, +21, -21, and -41° for (1R, αR)-1, (1R, αS)-1, (1S, αR)-1, and (1S, αS)-1, respectively. The stability of these compounds is very high at -20°C (no significant change for the optical rotation in 1 month). Enzyme kinetics and data reduction
|
(1R, αR)-1, (1R, αS)-1, (1S, αR)-1, and (1S, αS)-1
| null |
1H NMR (CDCl3, 300 MHz) δ/ppm 1.02 (d, J = 6.6 Hz, 3H, CH(Ph)CH3), 4.48 (quintet, J = 7 Hz, 1H, CH(Ph)CH3), 5.27 (d, J = 8.1 Hz, 1H, NH), 7.07–8.06 (m, 17H, aromatic H)
|
13C NMR (CDCl3, 75.4 MHz) δ/ppm 21.88 (CH3), 50.36 (CH(Ph)CH3), 122.45, 123.51, 125.43, 125.69, 126.08, 126.48, 126.60, 127.10, 127.24, 127.91, 128.18, 128.37, 128.53, 129.40, 131.40, 133.30, 133.41, 142.98, and 147.20 (aromatic Cs), 153.91 (C = O)
|
CDCl3, 300 MHz
|
1.02 (d, J = 6.6 Hz, 3H, CH(Ph)CH3), 4.48 (quintet, J = 7 Hz, 1H, CH(Ph)CH3), 5.27 (d, J = 8.1 Hz, 1H, NH), 7.07–8.06 (m, 17H, aromatic H)
|
CDCl3, 75.4 MHz
|
21.88, 50.36, 122.45, 123.51, 125.43, 125.69, 126.08, 126.48, 126.60, 127.10, 127.24, 127.91, 128.18, 128.37, 128.53, 129.40, 131.40, 133.30, 133.41, 142.98, 147.20, 153.91
| 0.723557
| 16,176,589
|
BMC Biochem. 2005 Sep 22; 6:17
|
BMC Biochem
| 2,005
|
CC BY
|
2021-01-04 16:26:24
|
no
|
PMC1274306
|
Preparation of 7-(4-bromo-n-butoxy)naringenin (1) Naringenin (136 mg, 0.5 mmol, 1.0 eq) was dissolved in acetone (5 mL), then potassium carbonate (69 mg, 0.5 mmol, 1.0 eq) was added and heated to reflux for 30 minutes. To this suspension, 1,4-dibromobutane (107 mg, 0.5 mmol, 1.0 eq) was added and stirred at reflux for 8 hours. After cooling to room temperature, the mixture was concentrated on a rotary evaporator to become a thick slurry. The slurry was re-dissolved in ethyl acetate (30 mL), washed with distilled water (three times with 10 mL) and brine (10 mL), then evaporated. Purification was performed by silica-gel column chromatography (3:1 hexanes/ethyl acetate) to give pure 7-(4-bromo-n-butoxy)naringenin as a white solid (132 mg, 65% yield): 1H NMR (acetone-d6, 250 MHz) δ 1.86–1.97 (m, 2H), 2.00–2.09 (m, 2H), 2.74 (dd, J = 17.0, 3.0 Hz, 1H), 3.19 (dd, J = 17.0, 12.8 Hz, 1H), 3.57 (t, J = 6.5 Hz, 2H), 4.11 (t, J = 6.3 Hz, 2H), 5.46 (d, J = 12.5 Hz, 1H), 6.03 (s, 1H), 6.04 (s, 1H), 6.89 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 8.48 (s, 1H), 12.11 (s, 1H); 13C NMR (acetone-d6, 62.9 MHz) δ 28.34, 30.18, 34.27, 43.46, 68.38, 79.98, 94.94, 95.88, 103.72, 116.17, 128.99, 130.67, 158.68, 164.15, 164.95, 168.09, 197.53.
|
7-(4-bromo-n-butoxy)naringenin
|
O=C1CC(C2=CC=C(O)C=C2)OC3=C1C(O)=CC(O)(OCCCCBr)=C3
|
1H NMR (acetone-d6, 250 MHz) δ 1.86–1.97 (m, 2H), 2.00–2.09 (m, 2H), 2.74 (dd, J = 17.0, 3.0 Hz, 1H), 3.19 (dd, J = 17.0, 12.8 Hz, 1H), 3.57 (t, J = 6.5 Hz, 2H), 4.11 (t, J = 6.3 Hz, 2H), 5.46 (d, J = 12.5 Hz, 1H), 6.03 (s, 1H), 6.04 (s, 1H), 6.89 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 8.48 (s, 1H), 12.11 (s, 1H)
|
13C NMR (acetone-d6, 62.9 MHz) δ 28.34, 30.18, 34.27, 43.46, 68.38, 79.98, 94.94, 95.88, 103.72, 116.17, 128.99, 130.67, 158.68, 164.15, 164.95, 168.09, 197.53
|
acetone-d6, 250 MHz
|
1.86–1.97 (m, 2H), 2.00–2.09 (m, 2H), 2.74 (dd, J = 17.0, 3.0 Hz, 1H), 3.19 (dd, J = 17.0, 12.8 Hz, 1H), 3.57 (t, J = 6.5 Hz, 2H), 4.11 (t, J = 6.3 Hz, 2H), 5.46 (d, J = 12.5 Hz, 1H), 6.03 (s, 1H), 6.04 (s, 1H), 6.89 (d, J = 8.3 Hz, 2H), 7.38 (d, J = 8.3 Hz, 2H), 8.48 (s, 1H), 12.11 (s, 1H)
|
acetone-d6, 62.9 MHz
|
28.34, 30.18, 34.27, 43.46, 68.38, 79.98, 94.94, 95.88, 103.72, 116.17, 128.99, 130.67, 158.68, 164.15, 164.95, 168.09, 197.53
| 0.949671
| 16,216,122
|
BMC Chem Biol. 2005 Oct 10; 5:3
|
BMC Chem Biol
| 2,005
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1310531
|
Others < 5 The 13C NMR signals of C-4 and C-5 in the pyrimidine ring of cytidine (1) also showed 13C13C satellites. The quantitative analysis revealed the presence of a [4,5-13C2]-isotopolog at a molar abundance of 0.1 mol% (Fig. 2) which was significantly above the natural abundance level (0.01 mol%). Moreover, the 1H NMR signal of H-6 (Fig. 4) showed 13C coupling satellites indicating a 13C abundance of 1.2 mol% for the [6-13C1]-isotopolog, i.e. 0.1 mol% excess over the natural 13C abundance of 1.1 mol% (see filled circle in Fig. 2). The presence of these isotopologs demonstrates that a fraction of the pyrimidine was biosynthesised de novo from the supplemented 13C-labelled glucose via aspartate (see below). The specific incorporation of the proffered 13C-glucose into the pyrimidine moiety can be estimated as 10–15% (Table 2). Figure 4 1H NMR signal of H-6 of cytidine from S. frugiperda cells grown with a 1:99 mixture of [U-13C6]glucose and unlabelled glucose added to SF-900 II medium. The amplitude of the satellites is 50-fold enlarged by comparison with the central signal. The coupling pattern is indicated.
|
cytidine
|
OC[C@@H]1[C@H]([C@H]([C@H](N2C(N=C(C=C2)N)=O)O1)O)O
|
The 1H NMR signal of H-6 (Fig. 4) showed 13C coupling satellites indicating a 13C abundance of 1.2 mol% for the [6-13C1]-isotopolog, i.e. 0.1 mol% excess over the natural 13C abundance of 1.1 mol% (see filled circle in Fig. 2)
|
The 13C NMR signals of C-4 and C-5 in the pyrimidine ring of cytidine (1) also showed 13C13C satellites. The quantitative analysis revealed the presence of a [4,5-13C2]-isotopolog at a molar abundance of 0.1 mol% (Fig. 2) which was significantly above the natural abundance level (0.01 mol%). Moreover, the 1H NMR signal of H-6 (Fig. 4) showed 13C coupling satellites indicating a 13C abundance of 1.2 mol% for the [6-13C1]-isotopolog, i.e. 0.1 mol% excess over the natural 13C abundance of 1.1 mol% (see filled circle in Fig. 2)
| null | null | null |
4, 5
| 0.000458
| 16,285,881
|
BMC Biochem. 2005 Nov 14; 6:24
|
BMC Biochem
| 2,005
|
CC BY
|
2021-01-04 16:26:24
|
no
|
PMC1310531
|
The purine ring systems of adenosine and guanosine showed no significantly increased levels of molecular species carrying two or more 13C atoms (Table 1). 1H NMR analysis showed no increased 13C abundance for the position 8 methine groups of both nucleosides. Consequently, the data demonstrate that purines were obtained from the culture medium and were not biosynthesised to a significant extent (> 5%) under the culture conditions (Table 2). Most amino acids obtained from the protein hydrolysate (i.e. leucine, phenylalanine, tyrosine, lysine, histidine, arginine, serine, threonine, valine, proline, methionine and isoleucine) showed only the low intensity 13C13C coupling satellites typical for natural abundance compounds. In contrast to the spectra of the amino acids mentioned above, the 13C NMR signals of alanine (4) were characterized by intense satellite signals due to couplings between adjacent 13C atoms. More specifically, the signal for C-2 showed a doublet indicating coupling to 13C-3, as well as a double-doublet indicating simultaneous coupling to 13C-3 and 13C-1. The relative fractions of these satellite pairs in the overall signal intensity of the C-2 signal accounted for 3.8 and 22.2%, respectively, which correspond to an abundance of 0.07 and 0.41 mol% for the [2,3-13C2]- and [U-13C3]-isotopolog (see also Table 3 and Fig. 5). On this basis, the specific incorporation of the 13C-glucose into alanine can be estimated as 45 – 50% (Table 2).
|
alanine
|
N[C@@H](C)C(O)=O
| null |
The 13C NMR signals of alanine (4) were characterized by intense satellite signals due to couplings between adjacent 13C atoms. The signal for C-2 showed a doublet indicating coupling to 13C-3, as well as a double-doublet indicating simultaneous coupling to 13C-3 and 13C-1
| null | null | null |
2,3-13C2, U-13C3
| 0.002756
| 16,285,881
|
BMC Biochem. 2005 Nov 14; 6:24
|
BMC Biochem
| 2,005
|
CC BY
|
2021-01-04 16:26:24
|
no
|
PMC1310531
|
The 15N NMR spectrum showed a signal at 35.8 ppm which was assigned to [15N]phenylalanine by internal standardization. The 15N abundance was determined by 13C NMR spectroscopy. The 13C NMR signals for C-2 and C-3 were accompanied by up-field shifted satellite signals due to 15N isotope shifts. The sizes of the isotope shifts for C-2 and C-3 (50.9 ppb and 37.6 ppb, respectively) as well as the 13C15N coupling constant of 3.7 Hz (1JCN) were in accordance with published values [5,6]. The relative fractions of the signal intensities of the up-field shifted satellites in the overall 13C NMR signal intensities of C-2 and C-3 accounted for 25 ± 2%. This value was confirmed by GC/MS of the N-trifluoroacetyl-n-butylester of phenylalanine [7]. A relative abundance of 30 ± 8% was determined for the 15N-labelled fragment (m/z = 216). Tyrosine isolated from cell protein was not 15N-labelled. Discussion
|
[15N]phenylalanine
| null | null |
The 13C NMR signals for C-2 and C-3 were accompanied by up-field shifted satellite signals due to 15N isotope shifts. The sizes of the isotope shifts for C-2 and C-3 (50.9 ppb and 37.6 ppb, respectively) as well as the 13C15N coupling constant of 3.7 Hz (1JCN) were in accordance with published values [5,6]
| null | null | null |
50.9, 37.6, 3.7
| 0.092786
| 16,285,881
|
BMC Biochem. 2005 Nov 14; 6:24
|
BMC Biochem
| 2,005
|
CC BY
|
2021-01-04 16:26:24
|
no
|
PMC1399459
|
3-Acetyl-5-nitrohexanoic acid methyl ester (2a) Purified by column chromatography (hexane/AcOEt, 7/3). 1H NMR (300 MHz, CDCl3) δ 1.55 (d, 3H, J = 6.7 Hz), 2.29 (s, 3H), 2.37–2.79 (2 m, 4 H), 2.92 (m, 1H), 3.67 (s, 3H), 4.55 (m, 1H); 13C NMR (75 MHz, CDCl3) δ 19.8, 29.8, 34.4, 36.2, 44.7, 52.0, 81.6, 171.4, 208.4. HRMS Calcd C9H15NO5: 217.0950. Found: 217.0932. Preparation of functionalized 1,4-diketones (3): General procedure
|
3-Acetyl-5-nitrohexanoic acid methyl ester
|
CC([N+]([O-])=O)CC(C(C)=O)CC(OC)=O
|
1H NMR (300 MHz, CDCl3) δ 1.55 (d, 3H, J = 6.7 Hz), 2.29 (s, 3H), 2.37–2.79 (2 m, 4 H), 2.92 (m, 1H), 3.67 (s, 3H), 4.55 (m, 1H)
|
13C NMR (75 MHz, CDCl3) δ 19.8, 29.8, 34.4, 36.2, 44.7, 52.0, 81.6, 171.4, 208.4
|
300 MHz, CDCl3
|
1.55 (d, 3H, J = 6.7 Hz), 2.29 (s, 3H), 2.37–2.79 (2 m, 4 H), 2.92 (m, 1H), 3.67 (s, 3H), 4.55 (m, 1H)
|
75 MHz, CDCl3
|
19.8, 29.8, 34.4, 36.2, 44.7, 52.0, 81.6, 171.4, 208.4
| 0.941618
| 16,542,022
|
Beilstein J Org Chem. 2005 Oct 7; 1:11
|
Beilstein J Org Chem
| 2,005
|
CC BY
|
2021-02-20 23:14:50
|
no
|
PMC1399459
|
3-Acetyl-5-oxohexanoic acid methyl ester (3a) Purified by column chromatography (hexane/AcOEt, 7/3). 1H NMR (300 MHz, CDCl3) δ 2.15 (s, 3H), 2.28 (s, 3H), 2.43; 2.65 (ABd, 2H, JAB = 16.5 Hz, JA-H = 7 Hz, JB-H = 6.6 Hz), 2.60; 2.93 (ABd, 2H, JAB = 18.1 Hz, JA-H = 8 Hz, JB-H = 5.5 Hz), 3.36 (m, 1H), 3.67 (s, 3H); 13C NMR (75 MHz, CDCl3) δ 29.2, 29.8, 35.0, 42.9, 44.4, 51.9, 172.0, 206.2, 209.5. HRMS Calcd C9H14O4: 186.0892. Found: 186.0877.
|
3-Acetyl-5-oxohexanoic acid methyl ester
|
CC(CC(C(C)=O)CC(OC)=O)=O
|
1H NMR (300 MHz, CDCl3) δ 2.15 (s, 3H), 2.28 (s, 3H), 2.43; 2.65 (ABd, 2H, JAB = 16.5 Hz, JA-H = 7 Hz, JB-H = 6.6 Hz), 2.60; 2.93 (ABd, 2H, JAB = 18.1 Hz, JA-H = 8 Hz, JB-H = 5.5 Hz), 3.36 (m, 1H), 3.67 (s, 3H)
|
13C NMR (75 MHz, CDCl3) δ 29.2, 29.8, 35.0, 42.9, 44.4, 51.9, 172.0, 206.2, 209.5
|
300 MHz, CDCl3
|
2.15 (s, 3H), 2.28 (s, 3H), 2.43; 2.65 (ABd, 2H, JAB = 16.5 Hz, JA-H = 7 Hz, JB-H = 6.6 Hz), 2.60; 2.93 (ABd, 2H, JAB = 18.1 Hz, JA-H = 8 Hz, JB-H = 5.5 Hz), 3.36 (m, 1H), 3.67 (s, 3H)
|
75 MHz, CDCl3
|
29.2, 29.8, 35.0, 42.9, 44.4, 51.9, 172.0, 206.2, 209.5
| 0.901676
| 16,542,022
|
Beilstein J Org Chem. 2005 Oct 7; 1:11
|
Beilstein J Org Chem
| 2,005
|
CC BY
|
2021-02-20 23:14:50
|
no
|
PMC1399459
|
4-Benzyl-3-methylcyclopent-2-enone (4d) Purified by column chromatography (hexane/AcOEt, 8/2). 1H NMR (300 MHz, CDCl3) δ 2.09 (s, 3H), 2.26–2.59 (m, 2H), 2.71 (m, 1H), 3.21 (m, 2H), 5.92 (s, 1H), 7.17–7.28 (m, 5H); 13C NMR (75 MHz, CDCl3) δ 19.4, 37.0, 39.0, 48.0, 126.3, 128.4, 128.8, 129.8, 139.6, 177.6, 211.0. HRMS Calcd C13H14O: 186.1045. Found: 186.1029 ==== Refs 1 Mikolajczyk M Grzejszczak S Midura W Zatorski A Phosphorus Sulfur Relat Elem 1983 18 175 178 2 Romanet R F Schlessinger R H J Am Chem Soc 1974 96 3701 3702 10.1021/ja00818a082
|
4-Benzyl-3-methylcyclopent-2-enone
|
CC(C(CC1=CC=CC=C1)C2)=CC2=O
|
1H NMR (300 MHz, CDCl3) δ 2.09 (s, 3H), 2.26–2.59 (m, 2H), 2.71 (m, 1H), 3.21 (m, 2H), 5.92 (s, 1H), 7.17–7.28 (m, 5H)
|
13C NMR (75 MHz, CDCl3) δ 19.4, 37.0, 39.0, 48.0, 126.3, 128.4, 128.8, 129.8, 139.6, 177.6, 211.0
|
300 MHz, CDCl3
|
2.09 (s, 3H), 2.26–2.59 (m, 2H), 2.71 (m, 1H), 3.21 (m, 2H), 5.92 (s, 1H), 7.17–7.28 (m, 5H)
|
75 MHz, CDCl3
|
19.4, 37.0, 39.0, 48.0, 126.3, 128.4, 128.8, 129.8, 139.6, 177.6, 211.0
| 0.970725
| 16,542,022
|
Beilstein J Org Chem. 2005 Oct 7; 1:11
|
Beilstein J Org Chem
| 2,005
|
CC BY
|
2021-02-20 23:14:50
|
no
|
PMC1479381
|
Experimental 2- [2-(2-Bromoethoxy)-2-oxoethyl]-5-nitrobenzoic acid (3a) (66% yield) Tan crystals: mp 113–115°C (lit. [25] 90°C);1H NMR: δ 3.50 (t, 2H, J = 5.96 Hz) 4.21 (s, 2H) 4.43 (t, 2H, J = 6.06 Hz) 7.51 (d, 1H, J = 8.34 Hz) 8.39 (dd, 1H, J = 2.59 Hz, 8.39 Hz) 8.98 (d, J = 2.39 Hz);13C NMR: δ 28.40, 40.13, 64.17, 126.24, 126.45, 130.97, 133.32, 142.59, 146.84, 167.46, 169.63.
|
2- [2-(2-Bromoethoxy)-2-oxoethyl]-5-nitrobenzoic acid
|
O=C(O)C1=CC([N+]([O-])=O)=CC=C1CC(OCCBr)=O
|
1H NMR: δ 3.50 (t, 2H, J = 5.96 Hz) 4.21 (s, 2H) 4.43 (t, 2H, J = 6.06 Hz) 7.51 (d, 1H, J = 8.34 Hz) 8.39 (dd, 1H, J = 2.59 Hz, 8.39 Hz) 8.98 (d, J = 2.39 Hz)
|
13C NMR: δ 28.40, 40.13, 64.17, 126.24, 126.45, 130.97, 133.32, 142.59, 146.84, 167.46, 169.63
| null |
3.50 (t, 2H, J = 5.96 Hz), 4.21 (s, 2H), 4.43 (t, 2H, J = 6.06 Hz), 7.51 (d, 1H, J = 8.34 Hz), 8.39 (dd, 1H, J = 2.59 Hz, 8.39 Hz), 8.98 (d, J = 2.39 Hz)
| null |
28.40, 40.13, 64.17, 126.24, 126.45, 130.97, 133.32, 142.59, 146.84, 167.46, 169.63
| 0.60075
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(3-Bromopropoxy)-2-oxoethyl]-5-nitrobenzoic acid (3b) (51% yield) White crystals: mp 122–123°C; 1H NMR: δ 2.19 (m, 2H) 3.44 (t, 2H, J = 6.56 Hz) 4.18 (s, 2H) 4.28 (t, 2H, J = 5.96 Hz) 7.51 (d, 1H, J = 8.34 Hz) 8.39 (dd, 1H, J = 2.39 Hz, 8.35 Hz) 8.98 (d, 1H, J = 2.18 Hz) 9.78 (br s, 1H); 13C NMR: δ 29.18, 31.58, 40.51, 63.12, 126.84, 127.52, 129.77, 143.37, 147.47, 169.92, 170.05.
|
2- [2-(3-Bromopropoxy)-2-oxoethyl]-5-nitrobenzoic acid
|
O=C(O)C1=CC([N+]([O-])=O)=CC=C1CC(OCCCBr)=O
|
1H NMR: δ 2.19 (m, 2H) 3.44 (t, 2H, J = 6.56 Hz) 4.18 (s, 2H) 4.28 (t, 2H, J = 5.96 Hz) 7.51 (d, 1H, J = 8.34 Hz) 8.39 (dd, 1H, J = 2.39 Hz, 8.35 Hz) 8.98 (d, 1H, J = 2.18 Hz) 9.78 (br s, 1H)
|
13C NMR: δ 29.18, 31.58, 40.51, 63.12, 126.84, 127.52, 129.77, 143.37, 147.47, 169.92, 170.05
| null |
2.19 (m, 2H), 3.44 (t, 2H, J = 6.56 Hz), 4.18 (s, 2H), 4.28 (t, 2H, J = 5.96 Hz), 7.51 (d, 1H, J = 8.34 Hz), 8.39 (dd, 1H, J = 2.39 Hz, 8.35 Hz), 8.98 (d, 1H, J = 2.18 Hz), 9.78 (br s, 1H)
| null |
29.18, 31.58, 40.51, 63.12, 126.84, 127.52, 129.77, 143.37, 147.47, 169.92, 170.05
| 0.567413
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(2-Bromoethoxy)-2-oxoethyl]benzoic acid (3c) (50% yield) Tan crystals: mp 82–83°C; 1H NMR: δ 3.50 (t, 2H, J = 6.25 Hz) 4.07 (s, 2H) 4.40 (t, 2H, J = 6.25 Hz) 7.27 (d, 1H, J = 7.75 Hz) 7.45 (t, 1H, J = 7.55 Hz) 7.54 (td, 1H, J = 1.39 Hz, 7.55 Hz) 8.14 (d, 1H, J = 7.74 Hz); 13C NMR: δ 28.50, 40.68, 64.08, 127.65, 128.32, 131.95, 132.43, 133.35, 136.40, 170.86, 172.43.
|
2- [2-(2-Bromoethoxy)-2-oxoethyl]benzoic acid
|
O=C(O)C1=CC=CC=C1CC(OCCBr)=O
|
1H NMR: δ 3.50 (t, 2H, J = 6.25 Hz) 4.07 (s, 2H) 4.40 (t, 2H, J = 6.25 Hz) 7.27 (d, 1H, J = 7.75 Hz) 7.45 (t, 1H, J = 7.55 Hz) 7.54 (td, 1H, J = 1.39 Hz, 7.55 Hz) 8.14 (d, 1H, J = 7.74 Hz)
|
13C NMR: δ 28.50, 40.68, 64.08, 127.65, 128.32, 131.95, 132.43, 133.35, 136.40, 170.86, 172.43
| null |
3.50 (t, 2H, J = 6.25 Hz), 4.07 (s, 2H), 4.40 (t, 2H, J = 6.25 Hz), 7.27 (d, 1H, J = 7.75 Hz), 7.45 (t, 1H, J = 7.55 Hz), 7.54 (td, 1H, J = 1.39 Hz, 7.55 Hz), 8.14 (d, 1H, J = 7.74 Hz)
| null |
28.50, 40.68, 64.08, 127.65, 128.32, 131.95, 132.43, 133.35, 136.40, 170.86, 172.43
| 0.63667
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(3-Bromopropoxy)-2-oxoethyl]benzoic acid (3d) (70% yield) White crystals: mp 79–80°C; 1H NMR: δ 2.16 (m, 2H, J = 6.31 Hz) 3.42 (t, 2H, J = 6.55 Hz) 4.05 (s, 2H) 4.24 (t, 2H, J = 5.96 Hz) 7.27 (d, 1H, J = 7.55 Hz) 7.40 (t, 1H, J = 7.65 Hz) 7.54 (td, 1H, J = 1.2, 7.35 Hz) 8.14 (dd, 1H, J = 0.99, 7.74 Hz); 13C NMR: δ 29.50, 31.80, 40.80, 62.52, 127.60, 128.35, 131.91, 132.41, 133.35, 136.86, 171.17, 172.47.
|
2- [2-(3-Bromopropoxy)-2-oxoethyl]benzoic acid
|
O=C(O)C1=CC=CC=C1CC(OCCCBr)=O
|
1H NMR: δ 2.16 (m, 2H, J = 6.31 Hz) 3.42 (t, 2H, J = 6.55 Hz) 4.05 (s, 2H) 4.24 (t, 2H, J = 5.96 Hz) 7.27 (d, 1H, J = 7.55 Hz) 7.40 (t, 1H, J = 7.65 Hz) 7.54 (td, 1H, J = 1.2, 7.35 Hz) 8.14 (dd, 1H, J = 0.99, 7.74 Hz)
|
13C NMR: δ 29.50, 31.80, 40.80, 62.52, 127.60, 128.35, 131.91, 132.41, 133.35, 136.86, 171.17, 172.47
| null |
2.16 (m, 2H, J = 6.31 Hz), 3.42 (t, 2H, J = 6.55 Hz), 4.05 (s, 2H), 4.24 (t, 2H, J = 5.96 Hz), 7.27 (d, 1H, J = 7.55 Hz), 7.40 (t, 1H, J = 7.65 Hz), 7.54 (td, 1H, J = 1.2, 7.35 Hz), 8.14 (dd, 1H, J = 0.99, 7.74 Hz)
| null |
29.50, 31.80, 40.80, 62.52, 127.60, 128.35, 131.91, 132.41, 133.35, 136.86, 171.17, 172.47
| 0.436206
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(4-Bromobutoxy)-2-oxoethyl]benzoic acid (3e) A solution of 4-bromo-1-butanol (2e, 6.0 mL, 41.6 mmol), homophthalic acid (1c, 2.5 g, 13.8 mmol), and five drops of concentrated sulfuric acid was refluxed in benzene (50 mL) for four hours. The solution was cooled and washed with water (2 × 25 mL), brine (1 × 25 mL), and dried over magnesium sulfate. Filtration and evaporation of the solvent gave a dark oil that was triturated with hexane to afford a crude solid. Recrystallization from hexane/ethyl acetate gave 0.91 g (40%) of compound 3e as white crystals: mp 84–86°C; 1H NMR: δ 1.79 (m, 2H) 1.87 (m, 2H) 3.38 (t, 2H, J = 6.45 Hz) 4.04 (s, 2H) 4.13 (t, 2H, J = 6.15 Hz) 7.27 (d, 1H, J = 7.55 Hz) 7.39 (t, 2H, J = 7.65 Hz) 7.54 (td, 1H, J = 1.4, 7.55 Hz) 8.13 (dd, 1H, J = 1.19, 7.74 Hz); 13C NMR: δ 27.33, 29.32, 33.19, 63.85, 127.56, 128.41, 131.88, 132.42, 133.33, 136.77, 171.32, 172.58.
|
2- [2-(4-Bromobutoxy)-2-oxoethyl]benzoic acid
|
O=C(O)C1=CC=CC=C1CC(OCCCCBr)=O
|
1H NMR: δ 1.79 (m, 2H) 1.87 (m, 2H) 3.38 (t, 2H, J = 6.45 Hz) 4.04 (s, 2H) 4.13 (t, 2H, J = 6.15 Hz) 7.27 (d, 1H, J = 7.55 Hz) 7.39 (t, 2H, J = 7.65 Hz) 7.54 (td, 1H, J = 1.4, 7.55 Hz) 8.13 (dd, 1H, J = 1.19, 7.74 Hz)
|
13C NMR: δ 27.33, 29.32, 33.19, 63.85, 127.56, 128.41, 131.88, 132.42, 133.33, 136.77, 171.32, 172.58
| null |
1.79 (m, 2H), 1.87 (m, 2H), 3.38 (t, 2H, J = 6.45 Hz), 4.04 (s, 2H), 4.13 (t, 2H, J = 6.15 Hz), 7.27 (d, 1H, J = 7.55 Hz), 7.39 (t, 2H, J = 7.65 Hz), 7.54 (td, 1H, J = 1.4, 7.55 Hz), 8.13 (dd, 1H, J = 1.19, 7.74 Hz)
| null |
27.33, 29.32, 33.19, 63.85, 127.56, 128.41, 131.88, 132.42, 133.33, 136.77, 171.32, 172.58
| 0.496514
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(2-Bromoethoxy)-4-chloro-7-nitro-1H-isochromen-1-one (4a) (43% yield) Yellow crystals: mp 126–128°C (lit. [25] 120°C); 1H NMR: δ 3.67 (t, 2H, J = 6.16 Hz) 4.74 (t, 2H, J = 6.06 Hz) 7.86 (d, 1H, J = 8.94 Hz) 8.53 (dd, 1H, J = 2.39 Hz, 8.94 Hz) 9.03 (d, 1H, J = 2.38 Hz); 13C NMR: δ 27.72, 69.63, 90.86, 117.17, 123.81, 126.32, 129.82, 142.71, 145.47, 154.77, 157.06.
|
3-(2-Bromoethoxy)-4-chloro-7-nitro-1H-isochromen-1-one
|
O=C1C2=C(C=CC([N+]([O-])=O)=C2)C(Cl)=C(OCCBr)O1
|
1H NMR: δ 3.67 (t, 2H, J = 6.16 Hz) 4.74 (t, 2H, J = 6.06 Hz) 7.86 (d, 1H, J = 8.94 Hz) 8.53 (dd, 1H, J = 2.39 Hz, 8.94 Hz) 9.03 (d, 1H, J = 2.38 Hz)
|
13C NMR: δ 27.72, 69.63, 90.86, 117.17, 123.81, 126.32, 129.82, 142.71, 145.47, 154.77, 157.06
| null |
3.67 (t, 2H, J = 6.16 Hz), 4.74 (t, 2H, J = 6.06 Hz), 7.86 (d, 1H, J = 8.94 Hz), 8.53 (dd, 1H, J = 2.39 Hz, 8.94 Hz), 9.03 (d, 1H, J = 2.38 Hz)
| null |
27.72, 69.63, 90.86, 117.17, 123.81, 126.32, 129.82, 142.71, 145.47, 154.77, 157.06
| 0.680596
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(3-Bromopropoxy)-4-chloro-7-nitro-1H-isochromen-1-one (4b) (76% yield) Pale yellow crystals: mp 131–134°C; 1H NMR: δ 2.37 (m, 2H) 3.59 (t, 2H, J = 6.26 Hz) 4.61 (t, 2H, J = 5.86 Hz) 7.81 (d, 1H, J = 8.94 Hz) 8.50 (dd, 1H, J = 2.09 Hz, 8.84 Hz) 8.99 (d, 1H, J = 1.79 Hz); 13C NMR: δ 28.49, 31.92, 68.56, 90.46, 116.93, 123.52, 126.22, 129.68, 142.77, 145.77, 155.34, 157.18.
|
3-(3-Bromopropoxy)-4-chloro-7-nitro-1H-isochromen-1-one
|
O=C1C2=C(C=CC([N+]([O-])=O)=C2)C(Cl)=C(OCCCBr)O1
|
1H NMR: δ 2.37 (m, 2H) 3.59 (t, 2H, J = 6.26 Hz) 4.61 (t, 2H, J = 5.86 Hz) 7.81 (d, 1H, J = 8.94 Hz) 8.50 (dd, 1H, J = 2.09 Hz, 8.84 Hz) 8.99 (d, 1H, J = 1.79 Hz)
|
13C NMR: δ 28.49, 31.92, 68.56, 90.46, 116.93, 123.52, 126.22, 129.68, 142.77, 145.77, 155.34, 157.18
| null |
2.37 (m, 2H), 3.59 (t, 2H, J = 6.26 Hz), 4.61 (t, 2H, J = 5.86 Hz), 7.81 (d, 1H, J = 8.94 Hz), 8.50 (dd, 1H, J = 2.09 Hz, 8.84 Hz), 8.99 (d, 1H, J = 1.79 Hz)
| null |
28.49, 31.92, 68.56, 90.46, 116.93, 123.52, 126.22, 129.68, 142.77, 145.77, 155.34, 157.18
| 0.616141
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(2-Bromoethoxy)-4-chloro-1H-isochromen-1-one (4c) (30% yield) Yellow solid: mp 81–82°C; 1H NMR: δ 3.65 (t, 2H, J = 6.35 Hz) 4.64 (t, 2H, J = 6.35 Hz) 7.41 (t, 1H, J = 7.15 Hz) 7.74 (m, 2H) 8.20 (d, 1H, J = 7.75 Hz); 13C NMR: δ 28.07, 69.37, 92.09, 117.53, 122.47, 126.55, 130.06, 135.62, 137.35, 152.08, 159.01.
|
3-(2-Bromoethoxy)-4-chloro-1H-isochromen-1-one
|
O=C1C2=C(C=CC=C2)C(Cl)=C(OCCBr)O1
|
1H NMR: δ 3.65 (t, 2H, J = 6.35 Hz) 4.64 (t, 2H, J = 6.35 Hz) 7.41 (t, 1H, J = 7.15 Hz) 7.74 (m, 2H) 8.20 (d, 1H, J = 7.75 Hz)
|
13C NMR: δ 28.07, 69.37, 92.09, 117.53, 122.47, 126.55, 130.06, 135.62, 137.35, 152.08, 159.01
| null |
3.65 (t, 2H, J = 6.35 Hz), 4.64 (t, 2H, J = 6.35 Hz), 7.41 (t, 1H, J = 7.15 Hz), 7.74 (m, 2H), 8.20 (d, 1H, J = 7.75 Hz)
| null |
28.07, 69.37, 92.09, 117.53, 122.47, 126.55, 130.06, 135.62, 137.35, 152.08, 159.01
| 0.664702
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(3-Bromopropoxy)-4-chloro-1H-isochromen-1-one (4d) (53% yield) Yellow crystals: mp 95–97°C; 1H NMR: δ 2.33 (m, 2H) 3.60 (t, 2H, J = 6.35 Hz) 4.51 (t, 2H, J = 5.76 Hz) 7.40 (t, 1H, J = 6.75 Hz) 7.72 (m, 2H) 8.19 (d, 1H, J = 7.94 Hz); 13C NMR: δ 28.88, 32.26, 68.28, 91.91, 117.58, 122.39, 126.43, 130.12, 135.62, 137.57, 152.74, 159.33.
|
3-(3-Bromopropoxy)-4-chloro-1H-isochromen-1-one
|
O=C1C2=C(C=CC=C2)C(Cl)=C(OCCCBr)O1
|
1H NMR: δ 2.33 (m, 2H) 3.60 (t, 2H, J = 6.35 Hz) 4.51 (t, 2H, J = 5.76 Hz) 7.40 (t, 1H, J = 6.75 Hz) 7.72 (m, 2H) 8.19 (d, 1H, J = 7.94 Hz)
|
13C NMR: δ 28.88, 32.26, 68.28, 91.91, 117.58, 122.39, 126.43, 130.12, 135.62, 137.57, 152.74, 159.33
| null |
2.33 (m, 2H), 3.60 (t, 2H, J = 6.35 Hz), 4.51 (t, 2H, J = 5.76 Hz), 7.40 (t, 1H, J = 6.75 Hz), 7.72 (m, 2H), 8.19 (d, 1H, J = 7.94 Hz)
| null |
28.88, 32.26, 68.28, 91.91, 117.58, 122.39, 126.43, 130.12, 135.62, 137.57, 152.74, 159.33
| 0.621532
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(4-Bromobutoxy)-4-chloro-1H-isochromen-1-one (4e) A solution of 3e (0.75 g, 2.3 mmol) and phosphorus pentachloride (1.23 g, 5.9 mmol) was refluxed in benzene (50 mL) for fourteen hours. The orange solution was cooled, washed with water (2 × 25 mL), saturated sodium bicarbonate (2 × 15 mL), brine (1 × 25 mL), and dried over magnesium sulfate. Filtration and evaporation of the solvent gave a yellow oil. Trituration with hexane gave 0.55 g (70%) of compound 4e as white crystals: mp 75–77°C; 1H NMR: δ 1.98 (m, 2H) 2.06 (m, 2H) 3.48 (t, 2H, J = 6.25 Hz) 4.40 (t, 2H, J = 5.96 Hz) 7.38 (td, 1H, J = 1.59 Hz, 7.50 Hz) 7.70 (m, 2H) 8.17 (d, 1H, J = 7.55 Hz); 13C NMR: δ 27.33, 29.32, 33.12, 40.80, 63.81, 127.55, 128.41. 131.86, 132.38, 133.30, 136.76, 171.26, 172.29. Exact mass calcd for C13H12BrClO3: 329.9658, observed (M+H) 330.9734.
|
3-(4-Bromobutoxy)-4-chloro-1H-isochromen-1-one
|
O=C1C2=C(C=CC=C2)C(Cl)=C(OCCCCBr)O1
|
1H NMR: δ 1.98 (m, 2H) 2.06 (m, 2H) 3.48 (t, 2H, J = 6.25 Hz) 4.40 (t, 2H, J = 5.96 Hz) 7.38 (td, 1H, J = 1.59 Hz, 7.50 Hz) 7.70 (m, 2H) 8.17 (d, 1H, J = 7.55 Hz)
|
13C NMR: δ 27.33, 29.32, 33.12, 40.80, 63.81, 127.55, 128.41. 131.86, 132.38, 133.30, 136.76, 171.26, 172.29
| null |
1.98 (m, 2H), 2.06 (m, 2H), 3.48 (t, 2H, J = 6.25 Hz), 4.40 (t, 2H, J = 5.96 Hz), 7.38 (td, 1H, J = 1.59 Hz, 7.50 Hz), 7.70 (m, 2H), 8.17 (d, 1H, J = 7.55 Hz)
| null |
27.33, 29.32, 33.12, 40.80, 63.81, 127.55, 128.41, 131.86, 132.38, 133.30, 136.76, 171.26, 172.29
| 0.399901
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(4-Chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide (5c) (64% yield) Yellow solid: mp 168–170°C (lit. [24] 167–169°C); 1H NMR: (DMSO-d6) δ 3.65 (t, 2H, J = 5.66 Hz) 4.58 (t, 2H, J = 5.67 Hz) 7.53 (t, 1H, J = 7.65 Hz) 7.69 (d, 1H, J = 8.14 Hz) 7.92 (t, 1H, J = 7.05 Hz) 8.13 (d, 1H, J = 7.75 Hz) 9.15 (br s, 4H); 13C NMR: δ 29.73, 68.11, 90.48, 117.18, 121.72, 126.70, 129.48, 135.99, 136.56, 152.18, 158.35, 169.11.
|
2- [2-(4-Chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
|
N=C(N)SCCOC(OC1=O)=C(Cl)C2=C1C=CC=C2.[H]Br
|
1H NMR: (DMSO-d6) δ 3.65 (t, 2H, J = 5.66 Hz) 4.58 (t, 2H, J = 5.67 Hz) 7.53 (t, 1H, J = 7.65 Hz) 7.69 (d, 1H, J = 8.14 Hz) 7.92 (t, 1H, J = 7.05 Hz) 8.13 (d, 1H, J = 7.75 Hz) 9.15 (br s, 4H)
|
13C NMR: δ 29.73, 68.11, 90.48, 117.18, 121.72, 126.70, 129.48, 135.99, 136.56, 152.18, 158.35, 169.11
|
DMSO-d6
|
3.65 (t, 2H, J = 5.66 Hz), 4.58 (t, 2H, J = 5.67 Hz), 7.53 (t, 1H, J = 7.65 Hz), 7.69 (d, 1H, J = 8.14 Hz), 7.92 (t, 1H, J = 7.05 Hz), 8.13 (d, 1H, J = 7.75 Hz), 9.15 (br s, 4H)
| null |
29.73, 68.11, 90.48, 117.18, 121.72, 126.70, 129.48, 135.99, 136.56, 152.18, 158.35, 169.11
| 0.607368
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [3-(4-Chloro-1-oxo-1H-isochromen-3-yloxy)propyl]isothiourea hydrobromide (5d) (40% yield) Yellow solid: mp 159–163°C (lit. [24] 165–167°C);1H NMR: (DMSO-d6) 2.21 (m, 2H) 3.40 (t, 2H, J = 7.18 Hz) 4.55 (t, 2H, J = 6.11 Hz) 7.62 (td, 1H, J = 0.95, 7.60 Hz) 7.79 (d, 1H, J = 7.70 Hz) 8.02 (td, 1H, J = 1.23, 7.70 Hz) 8.23 (dd, 1H, J = 1.25, 7.50 Hz) 10.09 (br s, 4H); 13C NMR: δ 26.66, 28.53, 68.68, 90.43, 117.13, 121.66, 126.59, 129.47, 135.96, 136.66, 152.63, 158.53, 169.36.
|
2- [3-(4-Chloro-1-oxo-1H-isochromen-3-yloxy)propyl]isothiourea hydrobromide
|
N=C(N)SCCCOC(OC1=O)=C(Cl)C2=C1C=CC=C2.[H]Br
|
1H NMR: (DMSO-d6) 2.21 (m, 2H) 3.40 (t, 2H, J = 7.18 Hz) 4.55 (t, 2H, J = 6.11 Hz) 7.62 (td, 1H, J = 0.95, 7.60 Hz) 7.79 (d, 1H, J = 7.70 Hz) 8.02 (td, 1H, J = 1.23, 7.70 Hz) 8.23 (dd, 1H, J = 1.25, 7.50 Hz) 10.09 (br s, 4H)
|
13C NMR: δ 26.66, 28.53, 68.68, 90.43, 117.13, 121.66, 126.59, 129.47, 135.96, 136.66, 152.63, 158.53, 169.36
|
DMSO-d6
|
2.21 (m, 2H), 3.40 (t, 2H, J = 7.18 Hz), 4.55 (t, 2H, J = 6.11 Hz), 7.62 (td, 1H, J = 0.95, 7.60 Hz), 7.79 (d, 1H, J = 7.70 Hz), 8.02 (td, 1H, J = 1.23, 7.70 Hz), 8.23 (dd, 1H, J = 1.25, 7.50 Hz), 10.09 (br s, 4H)
| null |
26.66, 28.53, 68.68, 90.43, 117.13, 121.66, 126.59, 129.47, 135.96, 136.66, 152.63, 158.53, 169.36
| 0.599596
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [4-(4-Chloro-1-oxo-1H-isochromen-3-yloxy)butyl]isothiourea hydrobromide (5e) A solution of 4e (0.25 g, 0.75 mmol) and thiourea (0.075 g, 0.98 mmol) in dry tetrahydrofuran (25 mL) was refluxed for forty-eight hours. The resulting pale yellow solid was filtered and washed with hot tetrahydrofuran (3 × 10 mL) to give 0.2 g (65%) of compound 5h as a pale yellow solid: mp 160–162°C; 1H NMR: (DMSO-d6) δ 1.82 (br s, 4H) 3.24 (t, 2H, J = 6.45 Hz) 4.39 (t, 2H, J = 5.75 Hz) 7.50 (t, 1H, J = 7.45 Hz) 7.65 (d, 1H, 7.45 Hz) 7.89 (t, 1H, J = 7.25 Hz) 8.09 (d, 1H, J = 7.75 Hz) 9.07 (br s, 4H); 13C NMR: δ 24.92, 27.35, 29.59, 69.96, 90.20, 116.95, 121.56, 126.48, 129.45, 135.94, 136.73, 152.80, 158.59, 169.56.
|
2- [4-(4-Chloro-1-oxo-1H-isochromen-3-yloxy)butyl]isothiourea hydrobromide
|
N=C(N)SCCCCOC(OC1=O)=C(Cl)C2=C1C=CC=C2.[H]Br
|
1H NMR: (DMSO-d6) δ 1.82 (br s, 4H) 3.24 (t, 2H, J = 6.45 Hz) 4.39 (t, 2H, J = 5.75 Hz) 7.50 (t, 1H, J = 7.45 Hz) 7.65 (d, 1H, 7.45 Hz) 7.89 (t, 1H, J = 7.25 Hz) 8.09 (d, 1H, J = 7.75 Hz) 9.07 (br s, 4H)
|
13C NMR: δ 24.92, 27.35, 29.59, 69.96, 90.20, 116.95, 121.56, 126.48, 129.45, 135.94, 136.73, 152.80, 158.59, 169.56
|
DMSO-d6
|
1.82 (br s, 4H), 3.24 (t, 2H, J = 6.45 Hz), 4.39 (t, 2H, J = 5.75 Hz), 7.50 (t, 1H, J = 7.45 Hz), 7.65 (d, 1H, 7.45 Hz), 7.89 (t, 1H, J = 7.25 Hz), 8.09 (d, 1H, J = 7.75 Hz), 9.07 (br s, 4H)
| null |
24.92, 27.35, 29.59, 69.96, 90.20, 116.95, 121.56, 126.48, 129.45, 135.94, 136.73, 152.80, 158.59, 169.56
| 0.446285
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
7-Amino-3-(2-bromoethoxy)-4-chloro-1H-isochromen-1-one (6a) Compound 4a (2.2 g, 6.3 mmol) was reduced on a Parr apparatus with hydrogen over 10% palladium on charcoal (50 mg) in ethanol (25 mL) until the reaction stopped absorbing hydrogen. The solution was filtered through celite and the filtrate was evaporated. The resulting crude solid was chromatographed (dichloromethane) to give 1.55 g (78%) of compound 6a as yellow crystals: mp 134–136°C, (lit. [26] 134–137°C); 1H NMR: δ 3.63 (t, 2H, J = 6.46 Hz) 3.95 (br s, 2H) 4.56 (t, 2H, J = 6.36 Hz) 7.10 (dd, 1H, J = 2.58 Hz, 8.54 Hz) 7.43 (d, 1H, J = 2.58 Hz) 7.54 (d, 1H, J = 8.74 Hz); 13C NMR: δ 28.18, 69.87, 93.59, 113.09, 119.21, 123.54, 124.04, 128.24, 145.63, 149.90, 159.47.
|
7-Amino-3-(2-bromoethoxy)-4-chloro-1H-isochromen-1-one
|
O=C1C2=C(C=CC(N)=C2)C(Cl)=C(OCCBr)O1
|
1H NMR: δ 3.63 (t, 2H, J = 6.46 Hz) 3.95 (br s, 2H) 4.56 (t, 2H, J = 6.36 Hz) 7.10 (dd, 1H, J = 2.58 Hz, 8.54 Hz) 7.43 (d, 1H, J = 2.58 Hz) 7.54 (d, 1H, J = 8.74 Hz)
|
13C NMR: δ 28.18, 69.87, 93.59, 113.09, 119.21, 123.54, 124.04, 128.24, 145.63, 149.90, 159.47
| null |
3.63 (t, 2H, J = 6.46 Hz), 3.95 (br s, 2H), 4.56 (t, 2H, J = 6.36 Hz), 7.10 (dd, 1H, J = 2.58 Hz, 8.54 Hz), 7.43 (d, 1H, J = 2.58 Hz), 7.54 (d, 1H, J = 8.74 Hz)
| null |
28.18, 69.87, 93.59, 113.09, 119.21, 123.54, 124.04, 128.24, 145.63, 149.90, 159.47
| 0.637429
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
7-Amino-3-(3-bromopropoxy)-4-chloro-1H-isochromen-1-one (6b) (75% yield) Yellow crystals: mp 106–107°C (lit. [24,26] 98–100°C); 1H NMR (DMSO-d6) δ 2.29 (m, 2H) 3.60 (t, 2H, J = 6.36 Hz) 4.42 (t, 2H, J = 5.76 Hz) 7.09 (dd, 1H, J = 2.09 Hz, 8.44 Hz) 7.42 (d, 1H, J = 1.99 Hz) 7.51 (d, 1H, J = 8.54 Hz); 13C NMR: δ 29.11, 32.36, 68.71, 93.35, 113.11, 119.17, 123.58, 123.91, 128.42, 145.56, 150.49, 159.74.
|
7-Amino-3-(3-bromopropoxy)-4-chloro-1H-isochromen-1-one
|
O=C1C2=C(C=CC(N)=C2)C(Cl)=C(OCCCBr)O1
|
1H NMR (DMSO-d6) δ 2.29 (m, 2H) 3.60 (t, 2H, J = 6.36 Hz) 4.42 (t, 2H, J = 5.76 Hz) 7.09 (dd, 1H, J = 2.09 Hz, 8.44 Hz) 7.42 (d, 1H, J = 1.99 Hz) 7.51 (d, 1H, J = 8.54 Hz)
|
13C NMR: δ 29.11, 32.36, 68.71, 93.35, 113.11, 119.17, 123.58, 123.91, 128.42, 145.56, 150.49, 159.74
|
DMSO-d6
|
2.29 (m, 2H), 3.60 (t, 2H, J = 6.36 Hz), 4.42 (t, 2H, J = 5.76 Hz), 7.09 (dd, 1H, J = 2.09 Hz, 8.44 Hz), 7.42 (d, 1H, J = 1.99 Hz), 7.51 (d, 1H, J = 8.54 Hz)
| null |
29.11, 32.36, 68.71, 93.35, 113.11, 119.17, 123.58, 123.91, 128.42, 145.56, 150.49, 159.74
| 0.577329
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(7-amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide (7a) (40% yield) Pale yellow solid: mp d 150°C; 1H NMR: (DMSO-d6) δ 3.59 (br s, 2H) 4.47 (br s, 2H) 5.81 (br s, 2H) 7.21 (d, 1H, J = 8.94 Hz) 7.26 (s, 1H) 7.44 (br d, 1H) 9.11 (br s, 4H);13C NMR: δ 29.73, 68.11, 90.48, 117.18, 121.72, 126.70, 129.48, 135.99, 136.56, 152.18, 158.35, 169.11.
|
2- [2-(7-amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
|
N=C(N)SCCOC(OC1=O)=C(Cl)C2=C1C=C(N)C=C2.[H]Br
|
1H NMR: (DMSO-d6) δ 3.59 (br s, 2H) 4.47 (br s, 2H) 5.81 (br s, 2H) 7.21 (d, 1H, J = 8.94 Hz) 7.26 (s, 1H) 7.44 (br d, 1H) 9.11 (br s, 4H)
|
13C NMR: δ 29.73, 68.11, 90.48, 117.18, 121.72, 126.70, 129.48, 135.99, 136.56, 152.18, 158.35, 169.11
|
DMSO-d6
|
3.59 (br s, 2H), 4.47 (br s, 2H), 5.81 (br s, 2H), 7.21 (d, 1H, J = 8.94 Hz), 7.26 (s, 1H), 7.44 (br d, 1H), 9.11 (br s, 4H)
| null |
29.73, 68.11, 90.48, 117.18, 121.72, 126.70, 129.48, 135.99, 136.56, 152.18, 158.35, 169.11
| 0.627578
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [3-(7-Amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)propyl]isothiourea hydrobromide (7b) A solution of 6b (0.25 g, 0.75 mmol), thiourea (0.071 g, 0.94 mmol) and tetrahydrofuran (25 mL) was refluxed for forty-eight hours to give a yellow precipitate. The precipitate was filtered and washed with hot tetrahydrofuran (3 × 25 mL), and recrystallized from methanol/ether to give 0.06 g (20%) of compound 7b as a pale yellow solid: mp 173°C; (lit. [24] 160–162°C); 1H NMR: (DMSO-d6) δ 2.07 (br s, 2H) 3.30 (br s, 2H) 4.32 (br s, 2H) 7.16 (d, 1H, J = 7.94 Hz) 7.26 (s, 1H) 7.41 (d, 1H, J = 7.95 Hz) 9.05 (br s, 4H);13C NMR: δ 26.73, 28.35, 69.26, 92.87, 110.88, 118.81, 122.84, 123.11, 124.66, 148.23, 149.41, 159.06, 169.37.
|
2- [3-(7-Amino-4-chloro-1-oxo-1H-isochromen-3-yloxy)propyl]isothiourea hydrobromide
|
N=C(N)SCCCOC(OC1=O)=C(Cl)C2=C1C=C(N)C=C2.[H]Br
|
1H NMR: (DMSO-d6) δ 2.07 (br s, 2H) 3.30 (br s, 2H) 4.32 (br s, 2H) 7.16 (d, 1H, J = 7.94 Hz) 7.26 (s, 1H) 7.41 (d, 1H, J = 7.95 Hz) 9.05 (br s, 4H)
|
13C NMR: δ 26.73, 28.35, 69.26, 92.87, 110.88, 118.81, 122.84, 123.11, 124.66, 148.23, 149.41, 159.06, 169.37
|
DMSO-d6
|
2.07 (br s, 2H), 3.30 (br s, 2H), 4.32 (br s, 2H), 7.16 (d, 1H, J = 7.94 Hz), 7.26 (s, 1H), 7.41 (d, 1H, J = 7.95 Hz), 9.05 (br s, 4H)
| null |
26.73, 28.35, 69.26, 92.87, 110.88, 118.81, 122.84, 123.11, 124.66, 148.23, 149.41, 159.06, 169.37
| 0.628242
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
N- [3-(2-Bromoethoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide (8a) To a solution of 6a (0.75 g, 2.4 mmol) in dry tetrahydrofuran (20 mL) was added benzoyl chloride (0.35 mL, 2.8 mmol) and triethylamine (0.33 mL, 2.3 mmol). The solution was stirred at room temperature for fourteen hours after which time the triethylamine hydrochloride was filtered off and washed with hot tetrahydrofuran (2 × 10 mL). The filtrate was evaporated to give a pale yellow solid that was recrystallized from tetrahydrofuran/hexane to afford 0.60 g (75%) of compound 8a as a pale yellow solid: mp 214–216°C; 1H NMR: (DMSO-d6) δ 3.83 (t, 2H, J = 5.46 Hz) 4.65 (t, 2H, J = 5.46 Hz) 7.56 (m, 3H) 7.71 (d, 1H, J = 8.93 Hz) 7.99 (d, 2H, J = 8.15) 8.29 (dd, 1H, J = 2.39 Hz, 8.74 Hz) 8.68 (d, 1H, J = 2.18 Hz) 10.63 (s, 1H); 13C NMR: δ 30.49, 69.98, 91.08, 117.64, 119.23, 122.38, 127.52, 127.86, 128.20, 131.62, 131.90, 134.12, 137.90, 151.40, 158.35, 165.43. Exact mass calcd for C18H13BrClNO4: 420.9716, observed (M+H) 421.9788.
|
N- [3-(2-Bromoethoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide
|
O=C(NC1=CC2=C(C=C1)C(Cl)=C(OCCBr)OC2=O)C3=CC=CC=C3
|
1H NMR: (DMSO-d6) δ 3.83 (t, 2H, J = 5.46 Hz) 4.65 (t, 2H, J = 5.46 Hz) 7.56 (m, 3H) 7.71 (d, 1H, J = 8.93 Hz) 7.99 (d, 2H, J = 8.15) 8.29 (dd, 1H, J = 2.39 Hz, 8.74 Hz) 8.68 (d, 1H, J = 2.18 Hz) 10.63 (s, 1H)
|
13C NMR: δ 30.49, 69.98, 91.08, 117.64, 119.23, 122.38, 127.52, 127.86, 128.20, 131.62, 131.90, 134.12, 137.90, 151.40, 158.35, 165.43
|
DMSO-d6
|
3.83 (t, 2H, J = 5.46 Hz), 4.65 (t, 2H, J = 5.46 Hz), 7.56 (m, 3H), 7.71 (d, 1H, J = 8.93 Hz), 7.99 (d, 2H, J = 8.15), 8.29 (dd, 1H, J = 2.39 Hz, 8.74 Hz), 8.68 (d, 1H, J = 2.18 Hz), 10.63 (s, 1H)
| null |
30.49, 69.98, 91.08, 117.64, 119.23, 122.38, 127.52, 127.86, 128.20, 131.62, 131.90, 134.12, 137.90, 151.40, 158.35, 165.43
| 0.612545
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
N- [3-(3-Bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide (8b) (82% yield) Pale yellow solid: mp 193–194°C; 1H NMR: (DMSO-d6) δ 2.28 (m, 2H) 3.66 (t, 2H, J = 6.56 Hz) 4.44 (t, 2H, J = 5.96 Hz) 7.55 (m, 3H) 7.68 (d, 1H, J = 8.74 Hz) 7.98 (d, 6.56 Hz) 8.25 (dd, 1H, J = 1.99 Hz, 8.74 Hz) 8.66 (d, 1H, J = 1.98 Hz) 10.62 (s, 1H); 13C NMR: δ 30.74, 32.09, 69.13, 91.36, 118.01, 119.74, 122.80, 127.88, 128.43, 128.67, 133.10, 132.46, 134.47, 138.15, 152.20, 158.95, 165.96. Exact mass calcd for C19H15BrClNO4: 434.9873, observed (M+H) 435.9959.
|
N- [3-(3-Bromopropoxy)-4-chloro-1-oxo-1H-isochromen-7-yl]benzamide
|
O=C(NC1=CC2=C(C=C1)C(Cl)=C(OCCCBr)OC2=O)C3=CC=CC=C3
|
1H NMR: (DMSO-d6) δ 2.28 (m, 2H) 3.66 (t, 2H, J = 6.56 Hz) 4.44 (t, 2H, J = 5.96 Hz) 7.55 (m, 3H) 7.68 (d, 1H, J = 8.74 Hz) 7.98 (d, 6.56 Hz) 8.25 (dd, 1H, J = 1.99 Hz, 8.74 Hz) 8.66 (d, 1H, J = 1.98 Hz) 10.62 (s, 1H)
|
13C NMR: δ 30.74, 32.09, 69.13, 91.36, 118.01, 119.74, 122.80, 127.88, 128.43, 128.67, 133.10, 132.46, 134.47, 138.15, 152.20, 158.95, 165.96
|
DMSO-d6
|
2.28 (m, 2H), 3.66 (t, 2H, J = 6.56 Hz), 4.44 (t, 2H, J = 5.96 Hz), 7.55 (m, 3H), 7.68 (d, 1H, J = 8.74 Hz), 7.98 (d, 6.56 Hz), 8.25 (dd, 1H, J = 1.99 Hz, 8.74 Hz), 8.66 (d, 1H, J = 1.98 Hz), 10.62 (s, 1H)
| null |
30.74, 32.09, 69.13, 91.36, 118.01, 119.74, 122.80, 127.88, 128.43, 128.67, 133.10, 132.46, 134.47, 138.15, 152.20, 158.95, 165.96
| 0.558359
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [2-(7-Benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide (9a) A solution of 8a (0.3 g, 0.71 mmol) and thiourea (0.06 g, 0.78 mmol) in dry tetrahydrofuran (25 mL) was refluxed for twelve hours. The resulting pale yellow solids were filtered and washed with hot tetrahydrofuran (3 × 10 mL) to give 0.06 g (17%) of compound 9a as a pale yellow solid: mp 173–175°C. Evaporation of the filtrate afforded 8a (0.2 g). Yield based on recovered starting material is 51%; 1H NMR: (DMSO-d6) δ 3.68 (br s, 2H) 4.60 (br s, 2H) 7.59 (m, 3H) 7.74 (d, 1H, J = 8.54 Hz) 8.03 (d, 2H, J = 6.75 Hz) 8.32 (d, 1H, J = 8.14 Hz) 8.73 (s, 1H) 9.18 (br s, 4H) 10.69 (s, 1H); 13C NMR: δ 29.85, 68.32, 91.00, 117.72, 119.47, 122.53, 127.60, 128.22, 128.33, 131.79, 132.06, 134.12, 137.96, 151.44, 158.43, 165.63, 169.18.
|
2- [2-(7-Benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy)ethyl]isothiourea hydrobromide
|
N=C(N)SCCOC(OC1=O)=C(Cl)C2=C1C=C(NC(C3=CC=CC=C3)=O)C=C2.[H]Br
|
1H NMR: (DMSO-d6) δ 3.68 (br s, 2H) 4.60 (br s, 2H) 7.59 (m, 3H) 7.74 (d, 1H, J = 8.54 Hz) 8.03 (d, 2H, J = 6.75 Hz) 8.32 (d, 1H, J = 8.14 Hz) 8.73 (s, 1H) 9.18 (br s, 4H) 10.69 (s, 1H)
|
13C NMR: δ 29.85, 68.32, 91.00, 117.72, 119.47, 122.53, 127.60, 128.22, 128.33, 131.79, 132.06, 134.12, 137.96, 151.44, 158.43, 165.63, 169.18
|
DMSO-d6
|
3.68 (br s, 2H), 4.60 (br s, 2H), 7.59 (m, 3H), 7.74 (d, 1H, J = 8.54 Hz), 8.03 (d, 2H, J = 6.75 Hz), 8.32 (d, 1H, J = 8.14 Hz), 8.73 (s, 1H), 9.18 (br s, 4H), 10.69 (s, 1H)
| null |
29.85, 68.32, 91.00, 117.72, 119.47, 122.53, 127.60, 128.22, 128.33, 131.79, 132.06, 134.12, 137.96, 151.44, 158.43, 165.63, 169.18
| 0.596585
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
2- [3-(7-Benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy]propyl)isothiourea hydrobromide (9b) (25% yield) Pale yellow solid: mp 203–204°C;1H NMR: (DMSO-d6) δ 2.12 (m, 2H) 3.31 (br s, 2H) 4.44 (t, 2H, J = 5.66 Hz) 7.56 (m, 3H) 7.71 (d, 1H, J = 8.74 Hz) 8.00 (d, 2H, J = 6.95 Hz) 8.28 (d, 1H, J = 8.54 Hz) 8.70 (s, 1H) 9.07 (br s, 4H) 10.65 (s, 1H); 13C NMR: δ 27.21, 28.79, 69.37, 91.38, 118.13, 119.85, 122.92, 128.04, 128.60, 128.77, 132.21, 132.57, 134.61, 138.33, 152.36, 159.05, 166.02, 169.83. Exact mass calcd for C20H18ClN3O4S: 431.0707, observed (M+H) 432.0780.
|
2- [3-(7-Benzamido-4-chloro-1-oxo-1H-isochromen-3-yloxy]propyl)isothiourea hydrobromide
| null |
1H NMR: (DMSO-d6) δ 2.12 (m, 2H) 3.31 (br s, 2H) 4.44 (t, 2H, J = 5.66 Hz) 7.56 (m, 3H) 7.71 (d, 1H, J = 8.74 Hz) 8.00 (d, 2H, J = 6.95 Hz) 8.28 (d, 1H, J = 8.54 Hz) 8.70 (s, 1H) 9.07 (br s, 4H) 10.65 (s, 1H)
|
13C NMR: δ 27.21, 28.79, 69.37, 91.38, 118.13, 119.85, 122.92, 128.04, 128.60, 128.77, 132.21, 132.57, 134.61, 138.33, 152.36, 159.05, 166.02, 169.83
|
DMSO-d6
|
2.12 (m, 2H), 3.31 (br s, 2H), 4.44 (t, 2H, J = 5.66 Hz), 7.56 (m, 3H), 7.71 (d, 1H, J = 8.74 Hz), 8.00 (d, 2H, J = 6.95 Hz), 8.28 (d, 1H, J = 8.54 Hz), 8.70 (s, 1H), 9.07 (br s, 4H), 10.65 (s, 1H)
| null |
27.21, 28.79, 69.37, 91.38, 118.13, 119.85, 122.92, 128.04, 128.60, 128.77, 132.21, 132.57, 134.61, 138.33, 152.36, 159.05, 166.02, 169.83
| 0.514382
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(2-Bromoethoxy)-7-nitro-1H-isochromen-1-one (10a) A solution of 3a (1.5 g, 4.5 mmol) and trifluoroacetic anhydride (0.64 mL, 5.0 mmol) in dichloromethane (50 mL) was stirred at room temperature for sixteen hours. The solution was evaporated, washed with water (1 × 25 mL), saturated sodium bicarbonate solution (1 × 25 mL), dried over magnesium sulfate, and evaporated to afford 1.23 g (87%) of a crude yellow solid. Recrystallization from isopropanol gave 0.66 g (47%) of compound 10a as yellow crystals: mp 95–97°C; 1H NMR: δ 3.65 (t, 2H, J = 5.96 Hz) 4.54 (t, 2H, J = 5.86 Hz) 5.77 (s, 1H) 7.42 (d, 1H, J = 8.74 Hz) 8.38 (d, 1H, J = 8.54 Hz) 8.96 (s, 1H); 13C NMR: δ 27.51, 68.87, 81.12, 117.12, 125.70, 126.17, 129.28, 144.97, 145.11, 158.81, 160.02.
|
3-(2-Bromoethoxy)-7-nitro-1H-isochromen-1-one
|
O=C1C2=C(C=CC([N+]([O-])=O)=C2)C=C(OCCBr)O1
|
1H NMR: δ 3.65 (t, 2H, J = 5.96 Hz) 4.54 (t, 2H, J = 5.86 Hz) 5.77 (s, 1H) 7.42 (d, 1H, J = 8.74 Hz) 8.38 (d, 1H, J = 8.54 Hz) 8.96 (s, 1H)
|
13C NMR: δ 27.51, 68.87, 81.12, 117.12, 125.70, 126.17, 129.28, 144.97, 145.11, 158.81, 160.02
| null |
3.65 (t, 2H, J = 5.96 Hz), 4.54 (t, 2H, J = 5.86 Hz), 5.77 (s, 1H), 7.42 (d, 1H, J = 8.74 Hz), 8.38 (d, 1H, J = 8.54 Hz), 8.96 (s, 1H)
| null |
27.51, 68.87, 81.12, 117.12, 125.70, 126.17, 129.28, 144.97, 145.11, 158.81, 160.02
| 0.677589
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(3-Bromopropoxy)-7-nitro-1H-isochromen-1-one (10b) (55% yield) Yellow crystals: mp 117–118°C; 1H NMR: δ 2.37 (m, 2H) 3.59 (t, 2H, J = 6.26 Hz) 4.38 (t, 2H, J = 5.86 Hz) 5.72 (s, 1H) 7.43 (d, 1H, J = 8.74 Hz) 8.41 (dd, 1H, J = 2.48 Hz, 8.84 Hz) 9.02 (d, 1H, J = 2.19 Hz);13C NMR: δ 28.80, 31.46, 67.29, 80.02, 117.02, 125.55, 126.07, 129.15, 144.79, 145.21, 158.94, 160.89.
|
3-(3-Bromopropoxy)-7-nitro-1H-isochromen-1-one
|
O=C1C2=C(C=CC([N+]([O-])=O)=C2)C=C(OCCCBr)O1
|
1H NMR: δ 2.37 (m, 2H) 3.59 (t, 2H, J = 6.26 Hz) 4.38 (t, 2H, J = 5.86 Hz) 5.72 (s, 1H) 7.43 (d, 1H, J = 8.74 Hz) 8.41 (dd, 1H, J = 2.48 Hz, 8.84 Hz) 9.02 (d, 1H, J = 2.19 Hz)
|
13C NMR: δ 28.80, 31.46, 67.29, 80.02, 117.02, 125.55, 126.07, 129.15, 144.79, 145.21, 158.94, 160.89
| null |
2.37 (m, 2H), 3.59 (t, 2H, J = 6.26 Hz), 4.38 (t, 2H, J = 5.86 Hz), 5.72 (s, 1H), 7.43 (d, 1H, J = 8.74 Hz), 8.41 (dd, 1H, J = 2.48 Hz, 8.84 Hz), 9.02 (d, 1H, J = 2.19 Hz)
| null |
28.80, 31.46, 67.29, 80.02, 117.02, 125.55, 126.07, 129.15, 144.79, 145.21, 158.94, 160.89
| 0.616135
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
3-(3-Bromopropoxy)-4-trifluoroacetyl-1H-isochromen-1-one (10c) A solution of 3d (0.60 g, 2.0 mmol) and trifluoroacetic anhydride (0.38 mL, 2.7 mmol) in dichloromethane (25 mL) was stirred at room temperature for fourteen hours. The solution was evaporated and the oil was chromatographed (chloroform) to afford 0.45 g (59%) of compound 10c as white crystals: mp 116–117°C; 1H NMR: δ 2.38 (m, 2H) 3.54 (t, 2H, J = 6.26 Hz) 4.70 (t, 2H, J = 5.96 Hz) 7.42 (m, 1H) 7.74 (m, 1H) 8.10 (d, 1H, J = 8.34 Hz) 8.22 (d, 1H, J = 7.95 Hz); 13C NMR: δ 28.24, 31.37, 68.94, 90.90, 115.81, 116.01, 123.40, 126.75, 130.26, 135.87, 136.27, 157.73, 162.08, 179.97. Anal. Calcd. for C14H10BrF3O4: C, 44.35; H, 2.66. Found: C, 44.25; H, 2.99.
|
3-(3-Bromopropoxy)-4-trifluoroacetyl-1H-isochromen-1-one
|
O=C1C2=C(C=CC=C2)C(C(C(F)(F)F)=O)=C(OCCCBr)O1
|
1H NMR: δ 2.38 (m, 2H) 3.54 (t, 2H, J = 6.26 Hz) 4.70 (t, 2H, J = 5.96 Hz) 7.42 (m, 1H) 7.74 (m, 1H) 8.10 (d, 1H, J = 8.34 Hz) 8.22 (d, 1H, J = 7.95 Hz)
|
13C NMR: δ 28.24, 31.37, 68.94, 90.90, 115.81, 116.01, 123.40, 126.75, 130.26, 135.87, 136.27, 157.73, 162.08, 179.97
| null |
2.38 (m, 2H), 3.54 (t, 2H, J = 6.26 Hz), 4.70 (t, 2H, J = 5.96 Hz), 7.42 (m, 1H), 7.74 (m, 1H), 8.10 (d, 1H, J = 8.34 Hz), 8.22 (d, 1H, J = 7.95 Hz)
| null |
28.24, 31.37, 68.94, 90.90, 115.81, 116.01, 123.40, 126.75, 130.26, 135.87, 136.27, 157.73, 162.08, 179.97
| 0.617115
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1479381
|
7-Amino-3-(2-bromoethoxy)-1H-isochromen-1-one (11) A solution of 10a (1.5 g, 4.7 mmol) in methanol/ethyl acetate (1:1, 25 mL) was reduced on a Parr apparatus with hydrogen and 10% palladium on charcoal. After the reaction stopped absorbing hydrogen it was filtered through celite and the celite was washed with methylene chloride (3 × 50 mL). The filtrate was evaporated to near dryness keeping the temperature below 40°C. The semisolid was recrystallized from methylene chloride/methanol to afford 1.10 g (81%) of compound 11 as yellow crystals: mp > 280°C; 1H NMR: (DMSO-d6) 3.79 (t, 2H, J = 5.17 Hz) 4.36 (t, 2H, J = 4.97 Hz) 5.50 (s, 2H) 5.82 (s, 1H) 7.03 (d, 1H, J = 8.54 Hz) 7.19 (m, 2H); 13C NMR: δ 30.30, 68.71, 80.35, 110.20, 117.91, 123.17, 125.84, 128.03, 147.16, 154.71, 160.45. Authors' contributions JJH conducted the synthetic chemistry with the assistance of LMD. LAH and TAV conducted the kinetic studies. DLVJ and LDM conceived the study and wrote the manuscript with the assistance of JJH.
|
7-Amino-3-(2-bromoethoxy)-1H-isochromen-1-one
|
O=C1C2=C(C=CC(N)=C2)C=C(OCCBr)O1
|
1H NMR: (DMSO-d6) 3.79 (t, 2H, J = 5.17 Hz) 4.36 (t, 2H, J = 4.97 Hz) 5.50 (s, 2H) 5.82 (s, 1H) 7.03 (d, 1H, J = 8.54 Hz) 7.19 (m, 2H)
|
13C NMR: δ 30.30, 68.71, 80.35, 110.20, 117.91, 123.17, 125.84, 128.03, 147.16, 154.71, 160.45
|
DMSO-d6
|
3.79 (t, 2H, J = 5.17 Hz), 4.36 (t, 2H, J = 4.97 Hz), 5.50 (s, 2H), 5.82 (s, 1H), 7.03 (d, 1H, J = 8.54 Hz), 7.19 (m, 2H)
| null |
30.30, 68.71, 80.35, 110.20, 117.91, 123.17, 125.84, 128.03, 147.16, 154.71, 160.45
| 0.665117
| 16,466,576
|
BMC Chem Biol. 2006 Feb 8; 6:1
|
BMC Chem Biol
| 2,006
|
CC BY
|
2021-01-04 16:30:50
|
no
|
PMC1686302
|
are presented in Table 5. The ligand H2L1 showed seven signals in the 13C-NMR spectra resonating at δ 131.91, 128.08, 126.70, 125.58, 123.92, 123.76, and 115.95 ppm for thirteen
|
H2L1
| null | null |
The ligand H2L1 showed seven signals in the 13C-NMR spectra resonating at δ 131.91, 128.08, 126.70, 125.58, 123.92, 123.76, and 115.95 ppm for thirteen
| null | null | null |
131.91, 128.08, 126.70, 125.58, 123.92, 123.76, 115.95
| 0.487334
| 17,497,005
|
Bioinorg Chem Appl. 2006 Mar 20; 2006:25651
|
Bioinorg Chem Appl
| 2,006
|
CC BY
|
2021-01-05 10:03:05
|
no
|
PMC1698928
|
3-Butyl-11-cyclopentyl-6,7,8,9-tetrahydrodiazepino [1,2,3-cd]purine-2,4-dione (18) To a solution of 8-butyl-10-cyclopentanecarboxamido-1,2,3,4,5,7,8,9-octahydropyrimido [1,6-c][1,3]diazepine-7,9-dione (16) [6] (0.17 g, 0.5 mmol) in THF (1 ml) in a 10 ml pressure vial, HMDS (1 ml) was added. Microwave irradiation was applied (200 W, 160°C) for 20 min. The resulting yellow solution was hydrolyzed with 4 ml of methanol while still warm (ca. 50°C). After the formation of ammonia gas had ceased, the liquid phase was distilled off under reduced pressure. The product was purified over a short silica gel column (5% EtOH in CH2Cl2 as eluent). Compound 18 (0.15 g, 91%) was obtained as a yellow oil (purity as determined by NMR: >95%). 1H-NMR (500 MHz, CDCl3) δ = 0.90 (t, 3H, J = 7.4 Hz, CH3), 1.35 (sex, J = 7.4 Hz, 2H), 1.61 (m, 4H), 1.81 (m, 2H), 1.99 (m, 4H), 2.16 (quint, 4H, J = 2.8 Hz), 3.04 (quint, 1H, J = 8.1 Hz), 3.99 (dd, 2H, J = 7.3 Hz, J = 7.4 Hz), 4.16 (m, 2H), 4.31 (m, 2H). 13C-NMR (500 MHz, CDCl3) δ = 13.83, 20.14, 25.23, 25.54, 25.61, 30.07, 31.37, 37.12, 41.57, 42.82, 43.46, 115.57, 141.03, 151.17, 151.66, 157.24. (1H-NMR [see Supporting Information File 7], 13C-NMR [see Supporting Information File 8], and IR [see Supporting Information File 9] spectra are added as additional files) Supporting Information File 1 1H-NMR of compound 5
|
3-Butyl-11-cyclopentyl-6,7,8,9-tetrahydrodiazepino [1,2,3-cd]purine-2,4-dione
| null |
1H-NMR (500 MHz, CDCl3) δ = 0.90 (t, 3H, J = 7.4 Hz, CH3), 1.35 (sex, J = 7.4 Hz, 2H), 1.61 (m, 4H), 1.81 (m, 2H), 1.99 (m, 4H), 2.16 (quint, 4H, J = 2.8 Hz), 3.04 (quint, 1H, J = 8.1 Hz), 3.99 (dd, 2H, J = 7.3 Hz, J = 7.4 Hz), 4.16 (m, 2H), 4.31 (m, 2H)
|
13C-NMR (500 MHz, CDCl3) δ = 13.83, 20.14, 25.23, 25.54, 25.61, 30.07, 31.37, 37.12, 41.57, 42.82, 43.46, 115.57, 141.03, 151.17, 151.66, 157.24
|
500 MHz, CDCl3
|
0.90 (t, 3H, J = 7.4 Hz, CH3), 1.35 (sex, J = 7.4 Hz, 2H), 1.61 (m, 4H), 1.81 (m, 2H), 1.99 (m, 4H), 2.16 (quint, 4H, J = 2.8 Hz), 3.04 (quint, 1H, J = 8.1 Hz), 3.99 (dd, 2H, J = 7.3 Hz, J = 7.4 Hz), 4.16 (m, 2H), 4.31 (m, 2H)
|
500 MHz, CDCl3
|
13.83, 20.14, 25.23, 25.54, 25.61, 30.07, 31.37, 37.12, 41.57, 42.82, 43.46, 115.57, 141.03, 151.17, 151.66, 157.24
| 0.921238
| 17,067,400
|
Beilstein J Org Chem. 2006 Oct 27; 2:20
|
Beilstein J Org Chem
| 2,006
|
CC BY
|
2021-02-20 23:14:52
|
no
|
PMC1803790
|
2. Results and discussions Cimicifoetiside A (1) (see Figure 1) exhibited a molecular formula of C37H58O10 based on its 13C-NMR DEPT spectrum and negative HRFABMS in which a fragment ion was observed at m/z 619.3854 [M-H-OAc]- (calcd for C35H55O9, 619.3846) due to the facile loss of an acetyl group. The overall physical properties and NMR spectral profile revealed its identity as a member of the cycloartane group of triterpene glycosides, a characteristic and distinguishable chemical marker of Cimicifuga plants. [6] In the 1H-NMR spectrum (Table 1), the characteristic cyclopropane methylene signals at δH 0.22 and 0.46 (each 1H, d, J = 3.0 Hz); eight methyl groups at δH 0.93, 1.05, 1.12, 1.18, 1.44, 1.47 (each 3H, s), 0.85 (d, J = 5.1 Hz), and an acetyl group at δ 2.09 (3H, s); and an anomeric proton at δH 4.75 (1H, d, J = 7.8 Hz) were observed. The 13C-NMR and DEPT spectra (Table 1), showed a total of 37 carbon signals, among which, 30 were ascribable to the triterpene aglycone. A characteristic ketalic quaternary carbon signal was observed at δC 112.0 (s, C-16) together with two oxygen-bearing methine signals at δC 80.3 (d, C-15) and 90.2 (d, C-24). Two carbons were assigned to an acetyl group [δC 170.2 and 21.4], and these spectra also showed a set of five oxygenated carbon signals assignable to a pentose moiety [δC 104.5 (C-1'), 74.4 (C-2'), 72.5 (C-3'), 69.8 (C-4'), and 67.3 (C-5')]. From the above information it was concluded that 1 was a cyclolanostane triterpene linked to a five carbon sugar unit with an acetyl group attached to either the triterpene aglycone or the sugar moiety. But the identities of the triterpene and the monosacchride, the sugar linkage position, and the acetyl group substitution position awaited determination.
|
Cimicifoetiside A
| null |
In the 1H-NMR spectrum (Table 1), the characteristic cyclopropane methylene signals at δH 0.22 and 0.46 (each 1H, d, J = 3.0 Hz); eight methyl groups at δH 0.93, 1.05, 1.12, 1.18, 1.44, 1.47 (each 3H, s), 0.85 (d, J = 5.1 Hz), and an acetyl group at δ 2.09 (3H, s); and an anomeric proton at δH 4.75 (1H, d, J = 7.8 Hz) were observed
|
The 13C-NMR and DEPT spectra (Table 1), showed a total of 37 carbon signals, among which, 30 were ascribable to the triterpene aglycone. A characteristic ketalic quaternary carbon signal was observed at δC 112.0 (s, C-16) together with two oxygen-bearing methine signals at δC 80.3 (d, C-15) and 90.2 (d, C-24). Two carbons were assigned to an acetyl group [δC 170.2 and 21.4], and these spectra also showed a set of five oxygenated carbon signals assignable to a pentose moiety [δC 104.5 (C-1'), 74.4 (C-2'), 72.5 (C-3'), 69.8 (C-4'), and 67.3 (C-5')]
| null |
0.22, 0.46 (each 1H, d, J = 3.0 Hz), 0.93, 1.05, 1.12, 1.18, 1.44, 1.47 (each 3H, s), 0.85 (d, J = 5.1 Hz), 2.09 (3H, s), 4.75 (1H, d, J = 7.8 Hz)
| null |
112.0, 80.3, 90.2, 170.2, 21.4, 104.5, 74.4, 72.5, 69.8, 67.3
| 0.159153
| 17,266,751
|
Beilstein J Org Chem. 2007 Jan 31; 3:3
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:54
|
no
|
PMC1803790
|
Figure 2 Key long-range 13C-1H correlations of 1 observed by HMBC. In the HMBC spectrum (See Figure 2), an informative correlation was also observed between the anomeric proton signal at δH 4.73 (H-1', 1H, J = 6.7 Hz) and a methine carbon signal at δC 88.7 (C-3), implying that the sugar moiety was linked at the C-3 position. The typical large coupling constants between H-1' and H-2' (JH1'-H2' = 6.7 Hz), and between H-2' and H-3' (JH2'-H3' = 6.7 Hz), as well as the small coupling constant between H-3' and H-4' (JH3'-H4' = 2.7 Hz) indicated the sugar moiety is a pentapyranose with the protons at C-1', C-2', and C-3' axially-oriented, while the proton at the C-4' position is equatorially disposed. Thus, the sugar moiety must be either a-L-arabinopyranosyl-[4C1 chair conformation) or β-D-arabinopyranosyl [1C4 chair conformation], with the former being more favorable, as it is a common component of the triterpene glycoside isolated from Cimicifuga plants, whereas the isolation of the latter has not been reported. Furthermore, the location of the acetyl group could be unambiguously assigned to C-2' of the arabinose unit by HMBC, as a correlation was observed between H-2' (δH 5.90, t, J = 6.7 Hz) and the carbonyl signal at δ 170.2. On mild alkali hydrolysis with saturated Na2CO3-MeOH solution, 1 afforded a deacetyl derivative which was shown to be cimigenol 3-α-L-arabinopyranoside, which is also a component isolated previously from CimicifugaI, [12] and was also isolated in the current investigation, by direct comparison from co-HPTLC and 1H-NMR spectroscopy with an authentic sample. Therefore, the structure of cimicifoetiside A (1) was unambiguously elucidated as cimigenol 3-O-α-L-(2'-O-acetyl) arabinopyranoside. Further evidence supporting this conclusion was derived by direct comparison of its 13C-NMR spectra with those of cimigenol 3-α-L-arabinopyranoside. It was found that all of the carbon signals were shown to be superimposable, except for the signals arising from C-1' (3.2 ppm up-field shifted), C-2' (1.2 ppm downfield shifted) and C-3' (2.4 ppm up-field shifted) in 1 compared to cimigenol 3-α-L-arabinopyranoside. This could be satisfactorily accounted for by the established 'acylation effect' [13] due to the introduction of an acetyl group at C-2' of cimigenol 3-α-L-arabinopyranoside.
|
cimicifoetiside A
| null |
In the HMBC spectrum (See Figure 2), an informative correlation was also observed between the anomeric proton signal at δH 4.73 (H-1', 1H, J = 6.7 Hz) and a methine carbon signal at δC 88.7 (C-3), implying that the sugar moiety was linked at the C-3 position. The typical large coupling constants between H-1' and H-2' (JH1'-H2' = 6.7 Hz), and between H-2' and H-3' (JH2'-H3' = 6.7 Hz), as well as the small coupling constant between H-3' and H-4' (JH3'-H4' = 2.7 Hz) indicated the sugar moiety is a pentapyranose with the protons at C-1', C-2', and C-3' axially-oriented, while the proton at the C-4' position is equatorially disposed. Thus, the sugar moiety must be either a-L-arabinopyranosyl-[4C1 chair conformation) or β-D-arabinopyranosyl [1C4 chair conformation], with the former being more favorable, as it is a common component of the triterpene glycoside isolated from Cimicifuga plants, whereas the isolation of the latter has not been reported. Furthermore, the location of the acetyl group could be unambiguously assigned to C-2' of the arabinose unit by HMBC, as a correlation was observed between H-2' (δH 5.90, t, J = 6.7 Hz) and the carbonyl signal at δ 170.2. On mild alkali hydrolysis with saturated Na2CO3-MeOH solution, 1 afforded a deacetyl derivative which was shown to be cimigenol 3-α-L-arabinopyranoside, which is also a component isolated previously from CimicifugaI, [12] and was also isolated in the current investigation, by direct comparison from co-HPTLC and 1H-NMR spectroscopy with an authentic sample. Therefore, the structure of cimicifoetiside A (1) was unambiguously elucidated as cimigenol 3-O-α-L-(2'-O-acetyl) arabinopyranoside
|
Furthermore, the location of the acetyl group could be unambiguously assigned to C-2' of the arabinose unit by HMBC, as a correlation was observed between H-2' (δH 5.90, t, J = 6.7 Hz) and the carbonyl signal at δ 170.2. On mild alkali hydrolysis with saturated Na2CO3-MeOH solution, 1 afforded a deacetyl derivative which was shown to be cimigenol 3-α-L-arabinopyranoside, which is also a component isolated previously from CimicifugaI, [12] and was also isolated in the current investigation, by direct comparison from co-HPTLC and 1H-NMR spectroscopy with an authentic sample. Therefore, the structure of cimicifoetiside A (1) was unambiguously elucidated as cimigenol 3-O-α-L-(2'-O-acetyl) arabinopyranoside
| null |
4.73 (H-1', 1H, J = 6.7 Hz), 88.7 (C-3), 5.90, t, J = 6.7 Hz (H-2'), 170.2 (carbonyl signal)
| null |
170.2
| 0.000048
| 17,266,751
|
Beilstein J Org Chem. 2007 Jan 31; 3:3
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:54
|
no
|
PMC1803790
|
Cimicifoetiside B (2) was determined to have a molecular formula of C39H60O11 based on its 13C-NMR (DEPT) spectral data and HRFABMS, in which a fragment ion was detected at m/z 661.3944 [M-H-OAc]- (calcd for C37H57O10, 661.3951) due to the loss of an acetyl group, indicating a 42 a.m.u. increase compared to that of 1, corresponding to the presence of an additional acetyl group (C2H2O). This is in agreement with the observation of an extra set of 1H and 13C-NMR signals for an acetyl group (δH 1.95, 3H, s; δC 170.2, s, and 22.3, q). The second acetyl group could be readily attributed to the hydroxyl group at C-25, as a significant downfield shift (12.1 ppm) of C-25, and up-field shifts of C-24 (3.2 ppm), C-26 (3.2 ppm), and C-27 (3.9 ppm) were observed in its 13C-NMR spectrum compared with those of 1, obeying the 'acylation effect' [13] with respect to acetylation occurring at the C-25 position, while the remaining carbon signals were almost identical. Following the same methodology as described for 1, all of the 1H and 13C-NMR spectral data of 2 were completely assigned. As shown in Figure 3, the HMBC experiment provided direct and conclusive evidence to assign one acetyl group to the C-2' position of arabinose; while indirect, but compelling, evidence for the assignment of the second acetyl group to C-25 was noted through the unambiguous assignment of the shifted signals of C-24, C-25, C-26, and C-27. The quaternary nature of C-25 prevented the linking of any proton signals to the carbonyl signal from HMBC (See Figure 3), except for the acetyl methyl group. Taken together, the structure of Cimicifoetiside B (2) was deduced as 25-O-acetylcimigenol 3-O-α-L-(2'-O-acetyl) arabinopyranoside.
|
25-O-acetylcimigenol 3-O-α-L-(2'-O-acetyl) arabinopyranoside
| null |
The second acetyl group could be readily attributed to the hydroxyl group at C-25, as a significant downfield shift (12.1 ppm) of C-25, and up-field shifts of C-24 (3.2 ppm), C-26 (3.2 ppm), and C-27 (3.9 ppm) were observed in its 13C-NMR spectrum compared with those of 1, obeying the 'acylation effect' [13] with respect to acetylation occurring at the C-25 position
|
The second acetyl group could be readily attributed to the hydroxyl group at C-25, as a significant downfield shift (12.1 ppm) of C-25, and up-field shifts of C-24 (3.2 ppm), C-26 (3.2 ppm), and C-27 (3.9 ppm) were observed in its 13C-NMR spectrum compared with those of 1, obeying the 'acylation effect' [13] with respect to acetylation occurring at the C-25 position
| null |
12.1, 3.2, 3.2, 3.9
| null |
12.1, 3.2, 3.2, 3.9
| 0.02004
| 17,266,751
|
Beilstein J Org Chem. 2007 Jan 31; 3:3
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:54
|
no
|
PMC1810298
|
Reaction of benzoxasilocines with aromatic aldehydes in the presence of BF3·Et2O We had previously observed [4] that the treatment of the seven membered cyclic allylsiloxane 2,3-dihydro-2,2-dimethylbenzo[f][1,2]oxasilepine with boron trifluoride yielded a ring-opened fluorinated derivative. This derivative was able to perform the condensation with aromatic aldehydes to generate the dihydrobenzofuran final products in the presence of a second equivalent of BF3·Et2O. In a similar way, when 5 is treated with BF3·Et2O in MeOH, the fluorinated species 6 is formed quantitatively (Scheme 3). The 1H NMR is very similar to that of the starting material, but for the methyl groups on silicon, which appear now as doublets due to their coupling with the 19F (3JH-F = 7.3 Hz). This coupling is also observed for the methylene on silicon H4', which exhibits now an additional splitting (3JH-F = 6.5 Hz) (for details see Supporting Information File 1). 13C NMR also reveals the presence of the fluorine on the silicon, because the signal due to the methyl groups appears as a doublet (2JC-F = 14.8 Hz) as well as the signal due to C4' (2JC-F = 13.5 Hz). 19F NMR shows only one signal at -160.73 ppm (hept t, 3JF-H = 7.3 Hz, 3JF-H = 6.5 Hz) with satellite bands due to the 19F-29Si coupling (2JF-Si = 283 Hz). A similar spectroscopic behaviour has been reported for other fluorosilanes. [4,21]
|
6
| null |
1H NMR is very similar to that of the starting material, but for the methyl groups on silicon, which appear now as doublets due to their coupling with the 19F (3JH-F = 7.3 Hz). This coupling is also observed for the methylene on silicon H4', which exhibits now an additional splitting (3JH-F = 6.5 Hz)
|
13C NMR also reveals the presence of the fluorine on the silicon, because the signal due to the methyl groups appears as a doublet (2JC-F = 14.8 Hz) as well as the signal due to C4' (2JC-F = 13.5 Hz)
| null |
7.3, 6.5
| null |
14.8, 13.5
| 0.08211
| 17,288,601
|
Beilstein J Org Chem. 2007 Feb 8; 3:5
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:55
|
no
|
PMC1847824
|
Results and Discussion The synthesis of 9-aryl-dimethyl-5,6,7,9-tetrahydro-1,2,4-triazolo-[5,1-b]quinazolin-8(4H)-ones by refluxing equimolar amounts of aromatic aldehydes (1, C6H5-, 4-OCH3-C6H4-, 4-NMe2-C6H4-, 4-Cl-C6H4- and 4-NO2C6H4-), 5-amino-1(H)-1,2,4-triazole (2) and dimedone (3) in DMF or methanol has been reported previously. [29–30] Fortunately, the microwave irradiation for the reaction containing the starting materials 1a-d, 2 and 3, afforded within a few minutes compounds 4a-d in nearly quantitative yields (Scheme 1). The products 4a,d are the same as obtained by the reported conventional procedure [29–30]. We chose another two aromatic aldehydes 1b,c and accordingly, we obtained the corresponding triazoloquinazolinones 4b,c as shown in Scheme 1. The structure of compounds 4b,c is in accord with the spectral data in IR, 1H NMR, 13C NMR and mass spectral data in addition to elemental analyses (see Supporting Information File 1 for full experimental data). The IR spectra of 4b,c revealed an intense carbonyl absorption band at νmax 1655-1650 cm-1 and a broad band was found in the range from 3390 to 3400 cm-1 due to the presence of a NH group. Analysis of the 1H NMR spectra of 4a-d provided answers on the chemoselectivity of the cyclocondensation. The δ values of the most carbon signals could be determined and assigned to the corresponding carbon atoms. For example, the 13C NMR spectrum of compound 4b revealed fourteen distinctive carbon signals at δC 192.0, 156.6, 150.1, 148.90, 133.8, 130.0, 128.8, 128.0, 127.6, 126.8, 113.0, 57.2, 98.8 and 49.8 corresponding to C-8, Ar-C-4a, CH-3, Ar-C-2', Ar-C-1', Ar-CH-6', Ar-CH-3', Ar-CH-4', C-5a, Ar-CH-5', C-8a, OCH3, CH-9, and C-7 respectively. The remaining carbon signals in compound 4b resonated at δ = 28.4 and 26.8 ppm could be assigned to the two methyl carbons (see Supporting Information File 1 for full experimental data).
|
9-aryl-dimethyl-5,6,7,9-tetrahydro-1,2,4-triazolo-[5,1-b]quinazolin-8(4H)-ones
|
O=C1C2=C(NC3=NC=NN3[C@H]2CCCCC)CC(C)C1C
|
The δ values of the most carbon signals could be determined and assigned to the corresponding carbon atoms
|
The 13C NMR spectrum of compound 4b revealed fourteen distinctive carbon signals at δC 192.0, 156.6, 150.1, 148.90, 133.8, 130.0, 128.8, 128.0, 127.6, 126.8, 113.0, 57.2, 98.8 and 49.8 corresponding to C-8, Ar-C-4a, CH-3, Ar-C-2', Ar-C-1', Ar-CH-6', Ar-CH-3', Ar-CH-4', C-5a, Ar-CH-5', C-8a, OCH3, CH-9, and C-7 respectively
| null | null | null |
192.0, 156.6, 150.1, 148.90, 133.8, 130.0, 128.8, 128.0, 127.6, 126.8, 113.0, 57.2, 98.8, 49.8
| 0.019771
| 17,338,816
|
Beilstein J Org Chem. 2007 Mar 5; 3:11
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:57
|
no
|
PMC1847824
|
via microwave irradiation. To test the reactivity of compounds 4a-c towards oxidation, we refluxed a mixture of 2,3,5,6-tetrachloro-1,4-benzoquinone (5) and 4a-c in cholorobenzene (Scheme 2). The reaction proceeded after long time of refluxing to give compounds 6a-c in good yields. The structure feature of the products 6a-c was confirmed by the IR, mass, 1H NMR and 13C NMR spectra in addition to elemental analyses. The IR spectra did not show any absorption due to the presence of NH group and this was also noted in the 1H NMR spectra. The disappearance of 9-H in the 1H NMR spectra and the appearance of C-5a in the 13C NMR spectra as an azomethine carbon signal at δ = 154.8–155.2 indicated that only the NH and 9-H protons were removed from the starting materials 4a-c (Scheme 2). The structure of the compounds in hand was confirmed to be that of dihydro-5H-[1,2,4]triazolo [5,1-b]-quinazolin-8-ones (Scheme 2).
|
6a-c
| null |
The IR spectra did not show any absorption due to the presence of NH group and this was also noted in the 1H NMR spectra. The disappearance of 9-H in the 1H NMR spectra and the appearance of C-5a in the 13C NMR spectra as an azomethine carbon signal at δ = 154.8–155.2 indicated that only the NH and 9-H protons were removed from the starting materials 4a-c
|
The IR spectra did not show any absorption due to the presence of NH group and this was also noted in the 1H NMR spectra. The disappearance of 9-H in the 1H NMR spectra and the appearance of C-5a in the 13C NMR spectra as an azomethine carbon signal at δ = 154.8–155.2 indicated that only the NH and 9-H protons were removed from the starting materials 4a-c
| null |
9-H
| null |
154.8–155.2
| 0.044731
| 17,338,816
|
Beilstein J Org Chem. 2007 Mar 5; 3:11
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:57
|
no
|
PMC1930152
|
Supporting Information Figure S1 13C-NMR analysis of the CFE from Pseudomonas fluorescens grown in a defined medium containing Ga-citrate. 2 mg/ml protein equivalent of CFE was incubated for 1h in a phosphate reaction buffer containing 5 mM Ga-13C2-2,4-citrate, 5 mM malonate, and NAD. The reaction was stopped by boiling for 5min and the sample was treated accordingly for NMR analysis. (2.43 MB TIF)
|
CFE
| null | null |
13C-NMR analysis of the CFE from Pseudomonas fluorescens grown in a defined medium containing Ga-citrate
| null | null | null |
5 mM Ga-13C2-2,4-citrate, 5 mM malonate, and NAD
| 0.067071
| 17,668,068
|
PLoS One. 2007 Aug 1; 2(8):e690
|
PLoS One
| 2,007
|
CC BY
|
2021-01-05 15:30:39
|
no
|
PMC1942119
|
To a stirred solution of methyl (2-bromothiophen-3-yl)acetate (120 mg, 0.51 mmol) and 4-iodo-3-nitrobenzoyl chloride (150 mg, 0.48 mmol) in anhydrous CH2Cl2 (10 mL) was added AlCl3 (260 mg, 1.95 mmol) in four portions at 10-minute intervals at room temperature. The resulting mixture was stirred overnight. The reaction mixture was slowly poured onto 5 g of ice and allowed to warm to room temperature. The aqueous phase was extracted with CH2Cl2 (3×15 mL). The combined organic layer was dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/5:1) of the residue gave 7 as a light yellow solid (158 mg, 61%). 1H NMR (400 MHz, CDCl3) δ 8.27 (d, 1H, J = 2.0 Hz), 8.22 (d, 1H, J = 8.0 Hz), 7.70 (dd, 1H, J = 2.0, 8.2 Hz), 7.48 (s, 1H), 3.74 (s, 3H) and 3.68 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 183.8, 170.0, 153.2, 142.9, 141.9, 138.3, 136.5, 135.8, 133.1, 125.7, 124.5, 91.8, 52.6 and 35.0; HRMS-ESI calcd C14H9BrINO5S [M+Na] 531.8322, found 531.8331.
|
7
| null |
1H NMR (400 MHz, CDCl3) δ 8.27 (d, 1H, J = 2.0 Hz), 8.22 (d, 1H, J = 8.0 Hz), 7.70 (dd, 1H, J = 2.0, 8.2 Hz), 7.48 (s, 1H), 3.74 (s, 3H) and 3.68 (s, 2H)
|
13C NMR (100 MHz, CDCl3) δ 183.8, 170.0, 153.2, 142.9, 141.9, 138.3, 136.5, 135.8, 133.1, 125.7, 124.5, 91.8, 52.6 and 35.0
|
400 MHz, CDCl3
|
8.27 (d, 1H, J = 2.0 Hz), 8.22 (d, 1H, J = 8.0 Hz), 7.70 (dd, 1H, J = 2.0, 8.2 Hz), 7.48 (s, 1H), 3.74 (s, 3H), 3.68 (s, 2H)
|
100 MHz, CDCl3
|
183.8, 170.0, 153.2, 142.9, 141.9, 138.3, 136.5, 135.8, 133.1, 125.7, 124.5, 91.8, 52.6, 35.0
| 0.787554
| 17,712,409
|
PLoS One. 2007 Aug 22; 2(8):e761
|
PLoS One
| 2,007
|
CC0
|
2021-01-05 15:30:42
|
no
|
PMC1942119
|
A solution of 7 (150 mg, 0.29 mmol), phenylacetylene (32 µL, 0.29 mmol), Pd(PPh3)2Cl2 (21 mg, 0.03 mmol), K2CO3 (42 mg, 0.29 mmol), and Et3N (40 µL, 0.29 mmol) in DMF (3 mL) was stirred for 24 hours at room temperature. Water (5 mL) was added to the mixture and then extracted with EtOAc (3×10 mL). The combined organic layer was washed with brine, dried over MgSO4, and concentrated in vacuo. MPLC purification (Hex:EtOAc/5:1) of the residue gave 8 as a solid foam (101 mg, 71 %). 1H NMR (400 MHz, CDCl3) δ 8.54 (d, 1H, J = 1.6 Hz,); 8.06 (dd, 1H, J = 1.6, 8.0 Hz), 7.86 (d, 1H, J = 8.4 Hz), 7.64 (m, 2H), 7.52 (s, 1H), 7.42 (m, 3H), 3.75 (s, 3H) and 3.70 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 183.9, 170.1, 149.5, 142.2, 137.0, 136.3, 135.7, 135.3, 132.9, 132.5, 130.1, 128.8, 125.6, 124.3, 122.8, 122.1, 101.1, 84.7, 52.7 and 35.0; HRMS-ESI calcd C22H14BrNO5S [M+Na] 505.9668, found 505.9666.
|
8
| null |
1H NMR (400 MHz, CDCl3) δ 8.54 (d, 1H, J = 1.6 Hz,); 8.06 (dd, 1H, J = 1.6, 8.0 Hz), 7.86 (d, 1H, J = 8.4 Hz), 7.64 (m, 2H), 7.52 (s, 1H), 7.42 (m, 3H), 3.75 (s, 3H) and 3.70 (s, 2H)
|
13C NMR (100 MHz, CDCl3) δ 183.9, 170.1, 149.5, 142.2, 137.0, 136.3, 135.7, 135.3, 132.9, 132.5, 130.1, 128.8, 125.6, 124.3, 122.8, 122.1, 101.1, 84.7, 52.7 and 35.0
|
400 MHz, CDCl3
|
8.54 (d, 1H, J = 1.6 Hz,), 8.06 (dd, 1H, J = 1.6, 8.0 Hz), 7.86 (d, 1H, J = 8.4 Hz), 7.64 (m, 2H), 7.52 (s, 1H), 7.42 (m, 3H), 3.75 (s, 3H), 3.70 (s, 2H)
|
100 MHz, CDCl3
|
183.9, 170.1, 149.5, 142.2, 137.0, 136.3, 135.7, 135.3, 132.9, 132.5, 130.1, 128.8, 125.6, 124.3, 122.8, 122.1, 101.1, 84.7, 52.7, 35.0
| 0.613109
| 17,712,409
|
PLoS One. 2007 Aug 22; 2(8):e761
|
PLoS One
| 2,007
|
CC0
|
2021-01-05 15:30:42
|
no
|
PMC1942119
|
To a solution of 8 (25 mg, 0.05 mmol) in EtOAc (5 mL) was added stannous chloride dihydrate (58 mg, 0.26 mmol). The resulting mixture was refluxed for one hour under N2. The reaction mixture was poured onto ice (5 g), and basified with saturated NaHCO3 solution to pH 8. The white milky mixture was filtered through a Celite pad to remove tin oxides. The organic layer from the filtrate was dried over MgSO4, filtered, and then concentrated in vacuo. MPLC purification (Hex:EtOAc/4:1) of the crude product gave the desired intermediate methyl (2-bromo-5-(3-amino-4-(phenylethynyl)benzoyl)thiophen-3-yl)acetate as a yellow foam (21 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.55 (m, 2H), 7.50 (s, 1H), 7.48 (d, 1H, J = 1.6 Hz), 7.38 (m, 3H), 7.17 (m, 2H), 4.40 (br, 2H), 3.73 (s, 3H) and 3.66 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 186.7, 170.3, 148.1, 143.4, 138.1, 135.9, 135.1, 132.4, 131.8, 129.0, 128.7, 122.9, 122.8, 118.8, 114.5, 112.3, 97.6, 85.3, 52.6 and 35.0; HRMS-ESI calcd C22H16BrNO3S [M+Na] 475.9926, found 475.9923.
|
methyl (2-bromo-5-(3-amino-4-(phenylethynyl)benzoyl)thiophen-3-yl)acetate
|
O=C(OC)CC1=C(Br)SC(C(C2=CC=C(C#CC3=CC=CC=C3)C(N)=C2)=O)=C1
|
1H NMR (400 MHz, CDCl3) δ 7.55 (m, 2H), 7.50 (s, 1H), 7.48 (d, 1H, J = 1.6 Hz), 7.38 (m, 3H), 7.17 (m, 2H), 4.40 (br, 2H), 3.73 (s, 3H) and 3.66 (s, 2H)
|
13C NMR (100 MHz, CDCl3) δ 186.7, 170.3, 148.1, 143.4, 138.1, 135.9, 135.1, 132.4, 131.8, 129.0, 128.7, 122.9, 122.8, 118.8, 114.5, 112.3, 97.6, 85.3, 52.6 and 35.0
|
400 MHz, CDCl3
|
7.55 (m, 2H), 7.50 (s, 1H), 7.48 (d, 1H, J = 1.6 Hz), 7.38 (m, 3H), 7.17 (m, 2H), 4.40 (br, 2H), 3.73 (s, 3H), 3.66 (s, 2H)
|
100 MHz, CDCl3
|
186.7, 170.3, 148.1, 143.4, 138.1, 135.9, 135.1, 132.4, 131.8, 129.0, 128.7, 122.9, 122.8, 118.8, 114.5, 112.3, 97.6, 85.3, 52.6, 35.0
| 0.773683
| 17,712,409
|
PLoS One. 2007 Aug 22; 2(8):e761
|
PLoS One
| 2,007
|
CC0
|
2021-01-05 15:30:42
|
no
|
PMC1942119
|
To a 250 mL flask containing freshly distilled toluene (50 mL) were added methyl (2-bromo-5-(3-amino-4-(phenylethynyl)benzoyl)thiophen-3-yl)acetate (2.93 g, 6.45 mmol) and indium tribromide (1.14 g, 3.22 mmol) under N2. The resulting mixture was refluxed for one hour. The solvent was removed in vacuo. MPLC purification (Hex:EtOAc/4:1) of the crude product gave 9 as a yellow solid (2.50 g, 85%). 1H NMR (400 MHz, CDCl3) δ 9.38 (br, 1H), 7.98 (s, 1H), 7.69 (d, 2H, J = 7.8 Hz), 7.58 (m, 2H), 7.47 (s, 1H), 7.40 (t, 2H, J = 7.5 Hz), 7.30 (m, 1 H), 6.80 (s, 1H), 3.65 (s, 3H) and 3.59 (s, 2H); 13C NMR (100 MHz, CDCl3) δ 187.4, 170.5, 144.2, 142.3, 136.5, 135.7, 134.9, 133.3, 131.8, 130.9, 129.4, 128.8, 125.9, 121.9, 120.4, 113.5, 100.3, 52.6 and 35.2; HRMS-ESI calcd C22H16BrNO3S [M+Na] 475.9926, found 475.9945.
|
9
| null |
1H NMR (400 MHz, CDCl3) δ 9.38 (br, 1H), 7.98 (s, 1H), 7.69 (d, 2H, J = 7.8 Hz), 7.58 (m, 2H), 7.47 (s, 1H), 7.40 (t, 2H, J = 7.5 Hz), 7.30 (m, 1 H), 6.80 (s, 1H), 3.65 (s, 3H) and 3.59 (s, 2H)
|
13C NMR (100 MHz, CDCl3) δ 187.4, 170.5, 144.2, 142.3, 136.5, 135.7, 134.9, 133.3, 131.8, 130.9, 129.4, 128.8, 125.9, 121.9, 120.4, 113.5, 100.3, 52.6 and 35.2
|
400 MHz, CDCl3
|
9.38 (br, 1H), 7.98 (s, 1H), 7.69 (d, 2H, J = 7.8 Hz), 7.58 (m, 2H), 7.47 (s, 1H), 7.40 (t, 2H, J = 7.5 Hz), 7.30 (m, 1 H), 6.80 (s, 1H), 3.65 (s, 3H), 3.59 (s, 2H)
|
100 MHz, CDCl3
|
187.4, 170.5, 144.2, 142.3, 136.5, 135.7, 134.9, 133.3, 131.8, 130.9, 129.4, 128.8, 125.9, 121.9, 120.4, 113.5, 100.3, 52.6, 35.2
| 0.538649
| 17,712,409
|
PLoS One. 2007 Aug 22; 2(8):e761
|
PLoS One
| 2,007
|
CC0
|
2021-01-05 15:30:42
|
no
|
PMC1942119
|
To a stirred solution of 9 (45 mg, 0.10 mmol) in anhydrous CH3CN (5 mL) was added CsF-Celite (125 mg) under N2, followed by adding N-(4-bromobutyl)-phthalimide (28 mg, 0.10 mmol). The resulting mixture was refluxed for five hours, cooled to room temperature, and filtered. The filtrate was evaporated in vacuo. MPLC purification (Hex:EtOAc/4:1) of the residue gave 10 as a yellow solid (28 mg, 43%). 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.74 (m, 6H), 7.59 (s, 1H), 7.47 (m, 5H), 6.60 (s, 1H), 4.32 (t, 2H, J = 7.2 Hz), 3.73 (s, 3H), 3.71 (s, 2H), 3.52 (t, 2H, J = 6.8 Hz), 1.72 (m, 2H) and 1.51 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 187.3, 170.4, 168.5, 145.2, 144.3, 136.8, 135.6, 134.9, 134.2, 134.1, 132.5, 132.1, 130.7, 129.5, 129.0, 128.8, 123.5, 123.4, 121.5, 120.6, 112.5, 103.1, 52.5, 43.7, 37.3, 35.1, 27.4 and 25.8; HRMS-ESI calcd C34H27BrN2O5S [M+Na] 677.0716, found 677.0727.
|
10
| null |
1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.74 (m, 6H), 7.59 (s, 1H), 7.47 (m, 5H), 6.60 (s, 1H), 4.32 (t, 2H, J = 7.2 Hz), 3.73 (s, 3H), 3.71 (s, 2H), 3.52 (t, 2H, J = 6.8 Hz), 1.72 (m, 2H) and 1.51 (m, 2H)
|
13C NMR (100 MHz, CDCl3) δ 187.3, 170.4, 168.5, 145.2, 144.3, 136.8, 135.6, 134.9, 134.2, 134.1, 132.5, 132.1, 130.7, 129.5, 129.0, 128.8, 123.5, 123.4, 121.5, 120.6, 112.5, 103.1, 52.5, 43.7, 37.3, 35.1, 27.4 and 25.8
|
400 MHz, CDCl3
|
7.98 (s, 1H), 7.74 (m, 6H), 7.59 (s, 1H), 7.47 (m, 5H), 6.60 (s, 1H), 4.32 (t, 2H, J = 7.2 Hz), 3.73 (s, 3H), 3.71 (s, 2H), 3.52 (t, 2H, J = 6.8 Hz), 1.72 (m, 2H), 1.51 (m, 2H)
|
100 MHz, CDCl3
|
187.3, 170.4, 168.5, 145.2, 144.3, 136.8, 135.6, 134.9, 134.2, 134.1, 132.5, 132.1, 130.7, 129.5, 129.0, 128.8, 123.5, 123.4, 121.5, 120.6, 112.5, 103.1, 52.5, 43.7, 37.3, 35.1, 27.4, 25.8
| 0.807789
| 17,712,409
|
PLoS One. 2007 Aug 22; 2(8):e761
|
PLoS One
| 2,007
|
CC0
|
2021-01-05 15:30:42
|
no
|
PMC1942119
|
To a solution of 3-hydroxyphenylboronic acid (32 mg, 0.23 mmol) in EtOH (1 mL, degassed with N2), was added a solution of 10 (153 mg, 0.23 mmol) in toluene (5 mL), followed by adding Pd(PPh3)2Cl2 (16.3 mg, 0.023 mmol) and Na2CO3 (50 mg, 0.46 mmol). The reaction mixture was refluxed for three hours under N2, and then the solvent was removed in vacuo. MPLC purification (Hex:EtOAc/2:1) of the residue gave 11 as a yellow solid (140 mg, 90%). 1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.70 (m, 2H), 7.64–7.59 (m, 4H), 7.42–7.33 (m, 6H), 7.24 (t, 1H, J = 7.9 Hz), 7.07 (t, 1H, J = 2.0 Hz), 6.97 (d, 1H, J = 7.6 Hz), 6.85 (dd, 1H, J = 2.0, 7.9 Hz), 6.52 (s, 1H), 4.23 (t, 2H, J = 7.0 Hz), 3.67 (s, 3H), 3.62 (s, 2H), 3.45 (t, 2H, J = 6.8 Hz), 1.67 (m, 2H) and 1.42 (m, 2H); 13C NMR (100 MHz, CDCl3) δ 188.6, 171.9, 168.8, 157.0, 149.2, 145.2, 141.6, 137.8, 136.7, 134.3, 132.6, 132.1, 131.3, 130.5, 130.4, 129.5, 129.0, 128.8, 123.5, 121.7, 121.3, 120.7, 116.5, 112.8, 103.2, 52.6, 43.7, 37.5, 34.6, 27.5 and 25.9; HRMS-ESI calcd C40H32N2O6S [M+Na] 691.1873, found 691.1892.
|
11
| null |
1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.70 (m, 2H), 7.64–7.59 (m, 4H), 7.42–7.33 (m, 6H), 7.24 (t, 1H, J = 7.9 Hz), 7.07 (t, 1H, J = 2.0 Hz), 6.97 (d, 1H, J = 7.6 Hz), 6.85 (dd, 1H, J = 2.0, 7.9 Hz), 6.52 (s, 1H), 4.23 (t, 2H, J = 7.0 Hz), 3.67 (s, 3H), 3.62 (s, 2H), 3.45 (t, 2H, J = 6.8 Hz), 1.67 (m, 2H) and 1.42 (m, 2H)
|
13C NMR (100 MHz, CDCl3) δ 188.6, 171.9, 168.8, 157.0, 149.2, 145.2, 141.6, 137.8, 136.7, 134.3, 132.6, 132.1, 131.3, 130.5, 130.4, 129.5, 129.0, 128.8, 123.5, 121.7, 121.3, 120.7, 116.5, 112.8, 103.2, 52.6, 43.7, 37.5, 34.6, 27.5 and 25.9
|
400 MHz, CDCl3
|
7.98 (s, 1H), 7.70 (m, 2H), 7.64–7.59 (m, 4H), 7.42–7.33 (m, 6H), 7.24 (t, 1H, J = 7.9 Hz), 7.07 (t, 1H, J = 2.0 Hz), 6.97 (d, 1H, J = 7.6 Hz), 6.85 (dd, 1H, J = 2.0, 7.9 Hz), 6.52 (s, 1H), 4.23 (t, 2H, J = 7.0 Hz), 3.67 (s, 3H), 3.62 (s, 2H), 3.45 (t, 2H, J = 6.8 Hz), 1.67 (m, 2H), 1.42 (m, 2H)
|
100 MHz, CDCl3
|
188.6, 171.9, 168.8, 157.0, 149.2, 145.2, 141.6, 137.8, 136.7, 134.3, 132.6, 132.1, 131.3, 130.5, 130.4, 129.5, 129.0, 128.8, 123.5, 121.7, 121.3, 120.7, 116.5, 112.8, 103.2, 52.6, 43.7, 37.5, 34.6, 27.5, 25.9
| 0.809587
| 17,712,409
|
PLoS One. 2007 Aug 22; 2(8):e761
|
PLoS One
| 2,007
|
CC0
|
2021-01-05 15:30:42
|
no
|
PMC1991597
|
Chemoenzymatic synthesis of coniferyl acetate ((E)-4-hydroxy-3-methoxycinnamylacetate) Coniferyl alcohol (180.2 mg, 1.0 mmol), Candida antarctica lipase B (CAL-B, 25 mg, Aldrich, ≥10,000 U/g), vinyl acetate (401 µL, 5.0 mmol), and dry diethyl ether (Et2O, 50 mL, 0.2 M) were stirred in a 125-mL Erlenmeyer flask at room temperature for 2 h (Figure 7). The reaction mixture was filtered through glass wool and concentrated in vacuo. The reaction yielded quantitatively the desired product (222 mg colorless oil). 1H NMR (500 MHz, CDCl3) δ 6.91 (m, 3H), 6.59 (d, J = 15.92 Hz, 1H), 6.15 (dt, J = 6.62, 15.92 Hz, 1H), 4.72 (d, J = 6.62 Hz, 2H), 3.92 (s, 3H), 2.11 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 171.2, 146.8, 146.1, 134.7, 129.0, 121.0, 120.9, 114.7, 108.6, 65.5, 56.1, 21.3. LCMS [M-H]- calculated for C12H13O4: 221.08, found: 221.2.
|
(E)-4-hydroxy-3-methoxycinnamylacetate
|
O=C([O-])CC/C=C/C1=CC=C(O)C(OC)=C1
|
1H NMR (500 MHz, CDCl3) δ 6.91 (m, 3H), 6.59 (d, J = 15.92 Hz, 1H), 6.15 (dt, J = 6.62, 15.92 Hz, 1H), 4.72 (d, J = 6.62 Hz, 2H), 3.92 (s, 3H), 2.11 (s, 3H)
|
13C NMR (125 MHz, CDCl3) δ 171.2, 146.8, 146.1, 134.7, 129.0, 121.0, 120.9, 114.7, 108.6, 65.5, 56.1, 21.3
|
500 MHz, CDCl3
|
6.91 (m, 3H), 6.59 (d, J = 15.92 Hz, 1H), 6.15 (dt, J = 6.62, 15.92 Hz, 1H), 4.72 (d, J = 6.62 Hz, 2H), 3.92 (s, 3H), 2.11 (s, 3H)
|
125 MHz, CDCl3
|
171.2, 146.8, 146.1, 134.7, 129.0, 121.0, 120.9, 114.7, 108.6, 65.5, 56.1, 21.3
| 0.54054
| 17,912,370
|
PLoS One. 2007 Oct 3; 2(10):e993
|
PLoS One
| 2,007
|
CC BY
|
2021-01-05 15:29:41
|
no
|
PMC1991597
|
4-((2-methoxyethoxy)methoxy)-3-methoxy benzaldehyde (step 1). K2CO3 (1.38 g, 10.0 mmol, 1.0 eq.) was added to solution of vanillin (1.52 g, 10.0 mmol, 1.0 eq.) in dry acetone (70 mL, 0.15 M), and the mixture was stirred under argon at 0°C for 30 min. Then MeOCH2CH2OCH2Cl (MEM-Cl, 1.49 g, 12.0 mmol, 1.2 eq.) was added drop wise, and the mixture was stirred an additional 5 h. The mixture was then concentrated in vacuo to ∼20 mL, combined with 20 mL of water, and extracted with diethyl ether (3×25 mL). The organic layers were pooled, washed with brine, dried with MgSO4, filtered and concentrated in vacuo. The resulting yellow oil (2.38 g, 98% yield) was used without further purification. 1H NMR (500 MHz, CDCl3) δ 9.86 (s, 1H), 7.43 (s, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 5.41 (s, 2H), 3.93 (s, 3H), 3.86 (t, J = 4.7 Hz, 2H), 3.54 (t, J = 4.7 Hz, 2H), 3.35 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 191.0, 152.0, 150.0, 131.1, 126.5, 114.8, 109.4, 94.0, 71.4, 68.2, 59.0, 56.0; LCMS [M+Na]+ calculated for C12H16O5Na: 263.09, found: 263.3.
|
4-((2-methoxyethoxy)methoxy)-3-methoxy benzaldehyde
|
O=CC1=CC=C(OCOCCOC)C(OC)=C1
|
1H NMR (500 MHz, CDCl3) δ 9.86 (s, 1H), 7.43 (s, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 5.41 (s, 2H), 3.93 (s, 3H), 3.86 (t, J = 4.7 Hz, 2H), 3.54 (t, J = 4.7 Hz, 2H), 3.35 (s, 3H)
|
13C NMR (125 MHz, CDCl3) δ 191.0, 152.0, 150.0, 131.1, 126.5, 114.8, 109.4, 94.0, 71.4, 68.2, 59.0, 56.0
|
500 MHz, CDCl3
|
9.86 (s, 1H), 7.43 (s, 1H), 7.42 (d, J = 8.5 Hz, 2H), 7.32 (d, J = 8.5 Hz, 2H), 5.41 (s, 2H), 3.93 (s, 3H), 3.86 (t, J = 4.7 Hz, 2H), 3.54 (t, J = 4.7 Hz, 2H), 3.35 (s, 3H)
|
125 MHz, CDCl3
|
191.0, 152.0, 150.0, 131.1, 126.5, 114.8, 109.4, 94.0, 71.4, 68.2, 59.0, 56.0
| 0.95673
| 17,912,370
|
PLoS One. 2007 Oct 3; 2(10):e993
|
PLoS One
| 2,007
|
CC BY
|
2021-01-05 15:29:41
|
no
|
PMC1991597
|
1-((2-methoxyethoxy)methoxy)-2-methoxy-4-vinylbenzene (step 2). To a suspension of methyltriphenylphosphonium bromide (MeP(Ph)3Br, 3.57 g, 10.0 mmol, 2.0 eq.) in anhydrous tetrahydrofuran (THF, 30 mL, 0.33 M), under argon at room temperature, was added potassium bis-trimethylsilylamide (KN(TMS)2, 4.5 mL, 9.0 mmol, 1.8 eq., 0.5 M in toluene). After 30 min, a solution containing 4-((2-methoxyethoxy)methoxy)-3-methoxy benzaldehyde (1.20 g, 5.0 mmol, 1.0 eq.) was added to the yellow colored ylide solution via cannula. The reaction was completed within 30–60 min (as monitored by TLC, hexanes/ethyl acetate, 7∶3). The reaction mixture was quenched with saturated NH4Cl and extracted with diethyl ether (3×100 mL). The organic layers were combined, washed with water (2×100 mL), brine (2×100 mL), dried over Na2SO4, filtered, concentrated in vacuo, and subjected to Dry Column Vacuum Chromatography (90% hexanes/ethyl acetate) to afford a colorless oil (2.01 g, 84% yield). 1H NMR (500 MHz, CDCl3) δ 7.15 (d, J = 8.3 Hz, 1H), 6.96 (s, 1H), 6.93 (d, J = 8.3 Hz, 1H), 6.65 (dd, J = 10.9, 17.5 Hz, 1H), 5.63 (d, J = 17.4 Hz, 1H), 5.32 (s, 2H), 5.17 (d, J = 10.9 Hz, 1H), 3.90 (s, 3H), 3.87 (t, J = 4.7 Hz, 2H), 3.56 (t, J = 4.7 Hz, 2H), 3.37 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 149.7, 146.4, 136.4, 132.3, 119.4, 116.2, 112.4, 109.1, 94.4, 71.5, 67.8, 59.0, 55.8; LCMS [M+Na]+ calculated for C13H18O4Na: 261.1, found: 260.9.
|
1-((2-methoxyethoxy)methoxy)-2-methoxy-4-vinylbenzene
|
C=CC1=CC=C(OCOCCOC)C(OC)=C1
|
1H NMR (500 MHz, CDCl3) δ 7.15 (d, J = 8.3 Hz, 1H), 6.96 (s, 1H), 6.93 (d, J = 8.3 Hz, 1H), 6.65 (dd, J = 10.9, 17.5 Hz, 1H), 5.63 (d, J = 17.4 Hz, 1H), 5.32 (s, 2H), 5.17 (d, J = 10.9 Hz, 1H), 3.90 (s, 3H), 3.87 (t, J = 4.7 Hz, 2H), 3.56 (t, J = 4.7 Hz, 2H), 3.37 (s, 3H)
|
13C NMR (125 MHz, CDCl3) δ 149.7, 146.4, 136.4, 132.3, 119.4, 116.2, 112.4, 109.1, 94.4, 71.5, 67.8, 59.0, 55.8
|
500 MHz, CDCl3
|
7.15 (d, J = 8.3 Hz, 1H), 6.96 (s, 1H), 6.93 (d, J = 8.3 Hz, 1H), 6.65 (dd, J = 10.9, 17.5 Hz, 1H), 5.63 (d, J = 17.4 Hz, 1H), 5.32 (s, 2H), 5.17 (d, J = 10.9 Hz, 1H), 3.90 (s, 3H), 3.87 (t, J = 4.7 Hz, 2H), 3.56 (t, J = 4.7 Hz, 2H), 3.37 (s, 3H)
|
125 MHz, CDCl3
|
149.7, 146.4, 136.4, 132.3, 119.4, 116.2, 112.4, 109.1, 94.4, 71.5, 67.8, 59.0, 55.8
| 0.906277
| 17,912,370
|
PLoS One. 2007 Oct 3; 2(10):e993
|
PLoS One
| 2,007
|
CC BY
|
2021-01-05 15:29:41
|
no
|
PMC1991597
|
(1S,2S)-ethyl 2-(4-hydroxy-3-methoxyphenyl) cyclo-propanecarboxylate (step 3). To a solution of copper-ligand complex prepared from CuIOTf (toluene)0.5 (129.3 mg, 0.25 mmol, 2.0 mol%) and ligand (A) (75.3 mg, 0.25 mmol, 2.0 mol%) in 50 mL of dry dichloromethane (DCM) was added 1-((2-methoxyethoxy)methoxy)-2-methoxy-4-vinylbenzene (1.0 g, 4.2 mmol, 1.0 eq.). Ethyl diazoacetate (CHN2CO2Et, 485.8 µL, 4.62 mmol, 1.1 eq.) was dissolved in 0.5 mL dry dichloromethane and added to the stirring reaction mixture by slow addition via syringe pump over 10 h. The crude reaction mixture was filtered through a plug of silica gel and concentrated in vacuo. 1H NMR and LCMS showed a complex product mixture consisting of 80% conversion to cyclopropane products with a trans to cis ratio of 2.5∶1. Chiral HPLC analysis (Chiralcel-OD) determined 95% ee for the trans product. In addition to the MEM-protected trans- and cis-cyclopropane products, the crude reaction mixture contained the desired final product, the deprotected trans-cyclopropane, (1S,2S)-ethyl 2-(4-hydroxy-3-methoxyphenyl) cyclo-propanecarboxylate (EMDF), which was isolated by column chromatography (90% hexanes/ethyl acetate → 100% ethyl acetate) (99.2 mg as a colorless oil, 10% yield). Subsequent X-ray structure analysis of EMDF complexed with EGS confirmed the compound's absolute stereochemistry. 1H NMR (500 MHz, CDCl3) δ 6.82 (d, J = 8.2 Hz, 1H), 6.64 (s, 1H), 6.59 (d, J = 8.2 Hz, 1H), 5.56, ( br s, Ar-OH, 1H), 4.17 (q, J = 7.0 Hz, 2H), 3.87 (s, 3H), 2.47 (ddd, J = 4.6, 6.4, 9.6 Hz, 1H), 1.82 (ddd, J = 4.6, 5.6, 8.8 Hz, 1H), 1.54 (ddd, J = 4.8, 5.6, 9.2 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H)1.25 (ddd, buried, 1H); 13C NMR (125 MHz, CDCl3) δ 173.6, 146.5, 144.3, 131.9, 118.8, 114.3, 109.4, 60.7, 55.9, 26.1, 23.8, 16.7, 14.3; LCMS [M-H]- calculated for C13H15O4Na: 235.1, found: 234.8. EGS enzyme assay
|
(1S,2S)-ethyl 2-(4-hydroxy-3-methoxyphenyl) cyclo-propanecarboxylate
|
O=C([C@@H]1[C@@H](C2=CC=C(O)C(OC)=C2)C1)OCC
|
1H NMR (500 MHz, CDCl3) δ 6.82 (d, J = 8.2 Hz, 1H), 6.64 (s, 1H), 6.59 (d, J = 8.2 Hz, 1H), 5.56, ( br s, Ar-OH, 1H), 4.17 (q, J = 7.0 Hz, 2H), 3.87 (s, 3H), 2.47 (ddd, J = 4.6, 6.4, 9.6 Hz, 1H), 1.82 (ddd, J = 4.6, 5.6, 8.8 Hz, 1H), 1.54 (ddd, J = 4.8, 5.6, 9.2 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H)1.25 (ddd, buried, 1H)
|
13C NMR (125 MHz, CDCl3) δ 173.6, 146.5, 144.3, 131.9, 118.8, 114.3, 109.4, 60.7, 55.9, 26.1, 23.8, 16.7, 14.3
|
500 MHz, CDCl3
|
6.82 (d, J = 8.2 Hz, 1H), 6.64 (s, 1H), 6.59 (d, J = 8.2 Hz, 1H), 5.56, ( br s, Ar-OH, 1H), 4.17 (q, J = 7.0 Hz, 2H), 3.87 (s, 3H), 2.47 (ddd, J = 4.6, 6.4, 9.6 Hz, 1H), 1.82 (ddd, J = 4.6, 5.6, 8.8 Hz, 1H), 1.54 (ddd, J = 4.8, 5.6, 9.2 Hz, 1H), 1.28 (t, J = 7.1 Hz, 3H)1.25 (ddd, buried, 1H)
|
125 MHz, CDCl3
|
173.6, 146.5, 144.3, 131.9, 118.8, 114.3, 109.4, 60.7, 55.9, 26.1, 23.8, 16.7, 14.3
| 0.352902
| 17,912,370
|
PLoS One. 2007 Oct 3; 2(10):e993
|
PLoS One
| 2,007
|
CC BY
|
2021-01-05 15:29:41
|
no
|
PMC1994063
|
Xylosylfructoside The 1D 1H and 13C NMR spectra of xylosylfructoside showed anomeric proton (δH 5.34 ppm, d, 3.7 Hz) and carbon (δC 93.17 ppm) signals for the xylopyranosyl residue. The 1H-1H coupling constant value between H-1-Xyl (δH 5.34 ppm, d, J = 3.7 Hz) and H-2-Xyl (δH 3.53 ppm, dd, J = 10.0 and 3.7 Hz) determined the α-form of the glycosyl bond. The 1H-1H-COSY and the HSQC spectra completed the assignment of the protons and carbons from H-1-Xyl to H-4-Xyl. The inter-residual HMBC correlation between H-1-Xyl (δH 5.34 ppm) and C-2-Fru (δC 104.55 ppm) determined the attachment between C-2-Fru and C-1-Xyl.
|
xylosylfructoside
|
OCC1([C@H]([C@@H]([C@@H](CO)O1)O)O)OC2[C@@H]([C@H]([C@@H](CO)O2)O)O
|
The 1D 1H and 13C NMR spectra of xylosylfructoside showed anomeric proton (δH 5.34 ppm, d, 3.7 Hz) and carbon (δC 93.17 ppm) signals for the xylopyranosyl residue. The 1H-1H coupling constant value between H-1-Xyl (δH 5.34 ppm, d, J = 3.7 Hz) and H-2-Xyl (δH 3.53 ppm, dd, J = 10.0 and 3.7 Hz) determined the α-form of the glycosyl bond. The 1H-1H-COSY and the HSQC spectra completed the assignment of the protons and carbons from H-1-Xyl to H-4-Xyl. The inter-residual HMBC correlation between H-1-Xyl (δH 5.34 ppm) and C-2-Fru (δC 104.55 ppm) determined the attachment between C-2-Fru and C-1-Xyl
|
The 1D 1H and 13C NMR spectra of xylosylfructoside showed anomeric proton (δH 5.34 ppm, d, 3.7 Hz) and carbon (δC 93.17 ppm) signals for the xylopyranosyl residue. The 1H-1H coupling constant value between H-1-Xyl (δH 5.34 ppm, d, J = 3.7 Hz) and H-2-Xyl (δH 3.53 ppm, dd, J = 10.0 and 3.7 Hz) determined the α-form of the glycosyl bond. The 1H-1H-COSY and the HSQC spectra completed the assignment of the protons and carbons from H-1-Xyl to H-4-Xyl. The inter-residual HMBC correlation between H-1-Xyl (δH 5.34 ppm) and C-2-Fru (δC 104.55 ppm) determined the attachment between C-2-Fru and C-1-Xyl
| null |
5.34, 3.53, 10.0, 3.7, 5.34, 104.55
| null |
93.17, 104.55
| 0.05955
| 17,880,747
|
Chem Cent J. 2007 Jun 28; 1:18
|
Chem Cent J
| 2,007
|
CC BY
|
2021-01-04 23:56:43
|
no
|
PMC1994063
|
Saccharide 1 The 1D 1H and 13C NMR spectra of saccharide 1 showed two anomeric proton (δH 5.11 ppm, d, 3.8 Hz and δH 5.59 ppm, d, 3.5 Hz) and carbon (δC 97.52 ppm and δC 90.84 ppm) signals for the xylopyranosyl and glucopyranosyl residues. The 1H-1H coupling constant between H-1 (δH 5.59 ppm, d, J = 3.5) and H-2 (δH 3.65 ppm, d, J = 9.8 and 3.5 Hz) of Xyl, and H-1 (δH 5.11 ppm, d, J = 3.8 Hz) and H-2 (δH 3.56 ppm, d, J = 10.1, 3.8 Hz) of Glc determined the α-form of the glycosyl bond. The 1H NMR spectrum showed a complex pattern in the region of δH 3.4–4.0 ppm. The 1H-1H-COSY and the HSQC spectra completed the assignment of the protons and carbons from H-1-Glc to H-6-Glc and from H-1-Xyl to H-4-Xyl. The inter-residual HMBC correlation between H-1-Xyl (δH 5.59 ppm) and C-2-Fru (δC 104.91 ppm), and H-1-Glc (δH 5.11 ppm) and C-2-Xyl (δC 76.39 ppm) indicated that C-2 of Fru and that of Xyl are attached to C-1-Xyl and C-1-Glc, respectively.
|
saccharide 1
| null |
The 1D 1H and 13C NMR spectra of saccharide 1 showed two anomeric proton (δH 5.11 ppm, d, 3.8 Hz and δH 5.59 ppm, d, 3.5 Hz) and carbon (δC 97.52 ppm and δC 90.84 ppm) signals for the xylopyranosyl and glucopyranosyl residues. The 1H-1H coupling constant between H-1 (δH 5.59 ppm, d, J = 3.5) and H-2 (δH 3.65 ppm, d, J = 9.8 and 3.5 Hz) of Xyl, and H-1 (δH 5.11 ppm, d, J = 3.8 Hz) and H-2 (δH 3.56 ppm, d, J = 10.1, 3.8 Hz) of Glc determined the α-form of the glycosyl bond. The 1H NMR spectrum showed a complex pattern in the region of δH 3.4–4.0 ppm. The 1H-1H-COSY and the HSQC spectra completed the assignment of the protons and carbons from H-1-Glc to H-6-Glc and from H-1-Xyl to H-4-Xyl. The inter-residual HMBC correlation between H-1-Xyl (δH 5.59 ppm) and C-2-Fru (δC 104.91 ppm), and H-1-Glc (δH 5.11 ppm) and C-2-Xyl (δC 76.39 ppm) indicated that C-2 of Fru and that of Xyl are attached to C-1-Xyl and C-1-Glc, respectively
|
The 1D 1H and 13C NMR spectra of saccharide 1 showed two anomeric proton (δH 5.11 ppm, d, 3.8 Hz and δH 5.59 ppm, d, 3.5 Hz) and carbon (δC 97.52 ppm and δC 90.84 ppm) signals for the xylopyranosyl and glucopyranosyl residues
| null |
5.11, 5.59
| null |
97.52, 90.84
| 0.079301
| 17,880,747
|
Chem Cent J. 2007 Jun 28; 1:18
|
Chem Cent J
| 2,007
|
CC BY
|
2021-01-04 23:56:43
|
no
|
PMC2071920
|
Synthesis of Bio-ITC [4-(4-Isothiocyanato-butyl)-tetrahydro-thieno[3,4-d]imidazol-2-one] A solution of norbiotinamine hydrochloride (10 mg, 0.040 mmol) dissolved in acetonitrile (2 mL) and chloroform (0.40 mL) was prepared in a flame dried flask under Ar(g). A solution of TCDP (10 mg, 0.040 mmol) in chloroform (0.40 mL) was added to the previously prepared solution. Following 15 minutes of continued stirring, one drop of triethylamine was added. The yellow-orange color was diminished upon addition. After 45 minutes, an additional drop of triethylamine was added and the reaction's progress was followed by thin layer chromatography (TLC). After four hours, the starting material was consumed and the reaction was concentrated to a crude material that was purified by normal phase preparative-TLC (Silica Gel GF®, 500 microns, Analtech) using 1:9 methanol/chloroform as an eluent. Following separation, the desired band was carefully isolated from the plate and washed through a fritted funnel with multiple portions of ethyl acetate. The organic solvent was concentrated to 7 mG (70%) of the title compound as a off-white powdery solid. Rf (10% MeOH in CHCl3) = 0.22. 1H NMR (300 MHz, CD3OD, 23°C, δ): 4.50 (dd, J = 7.9, 5.1 Hz, 1 H), 4.33 (dd, J = 7.1, 4.5 Hz, 1 H), 3.58 (t, J = 6.5 Hz, 2 H), 2.95 (dd, J = 12.8, 5.1 Hz, 1 H), 2.72 (d, J = 12.8 Hz, 1 H), 1.83–1.52 (m, 6 H) ppm. 13C NMR (300 MHz, CD3OD, 23°C, δ): 168.30, 125.85, 63.41, 61.63, 56.90, 41.05, 31.00, 29.08, 27.33 ppm. MS (ESI+) m/z 258 [M+H]+. BioITC labeling reactions Untreated or PEITC treated cells were lysed in Tris lysis buffer (50 mM Tris pH7.8, 0.1% NP-40) supplemented with 2.5 μg/ml aprotinin and 2.5 μg/ml leupeptin. Lysates were clarified by centrifugation at 14,000 × g for 5 minutes. Clarified lysates were reacted with 500 μM Bio-ITC for 30 minutes at room temperature. Samples were removed for in vitro kinase assay, cell lysate immunoblots, and/or chitin bead purification and immunoblot analysis, as indicated in the figure legends.
|
Bio-ITC
| null |
1H NMR (300 MHz, CD3OD, 23°C, δ): 4.50 (dd, J = 7.9, 5.1 Hz, 1 H), 4.33 (dd, J = 7.1, 4.5 Hz, 1 H), 3.58 (t, J = 6.5 Hz, 2 H), 2.95 (dd, J = 12.8, 5.1 Hz, 1 H), 2.72 (d, J = 12.8 Hz, 1 H), 1.83–1.52 (m, 6 H) ppm
|
13C NMR (300 MHz, CD3OD, 23°C, δ): 168.30, 125.85, 63.41, 61.63, 56.90, 41.05, 31.00, 29.08, 27.33 ppm
|
300 MHz, CD3OD, 23°C, δ
|
4.50 (dd, J = 7.9, 5.1 Hz, 1 H), 4.33 (dd, J = 7.1, 4.5 Hz, 1 H), 3.58 (t, J = 6.5 Hz, 2 H), 2.95 (dd, J = 12.8, 5.1 Hz, 1 H), 2.72 (d, J = 12.8 Hz, 1 H), 1.83–1.52 (m, 6 H)
|
300 MHz, CD3OD, 23°C, δ
|
168.30, 125.85, 63.41, 61.63, 56.90, 41.05, 31.00, 29.08, 27.33
| 0.336089
| 17,894,894
|
BMC Cancer. 2007 Sep 25; 7:183
|
BMC Cancer
| 2,007
|
CC BY
|
2021-01-04 16:46:16
|
no
|
PMC2157549
|
Fig. 4 Glycosyl linkage analysis of LM from C. glutamicum and Cg-t-LM from C. glutamicumΔmptA. Per-O-methylated samples were hydrolysed using 2 M trifluoroacetic acid, reduced and per-O-acetylated. The resulting partially per-O-methylated, per-O-acetylated alditol acetates from C. glutamicum LM (A) and C. glutamicumΔmptA Cg-t-LM (B) were analysed by GC/MS (Tatituri et al., 2007). The extracted LM from C. glutamicum and C. glutamicumΔmptA were analysed by matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS). The negative MALDI-TOF-MS spectrum of Cg-LM showed a broad unresolved peak centred at m/z 5700 (Fig. 5A), indicating a molecular mass of approximately 5.7 kDa for the major molecular species of this lipoglycan. Analysis of Cg-t-LM from C. glutamicumΔmptA (Fig. 5B) produced a lower average molecular mass of approximately 3.3 kDa, proposing a composition based on extension of Ac1PIM2 (m/z 1398) (Tatituri et al., 2007) to afford Cg-t-LM as an average molecule centred on Ac1PIM14. As highlighted in our previous studies, the carbohydrate backbone of Cg-LM has been shown to be composed of an α(1→6)Manp backbone substituted at most of the O-2 positions by t-Manp and t-Manp-α-d-(1→2)-Manp units (Tatituri et al., 2007). The different nuclear magnetic resonance (NMR) spin systems of Cg-LM and Cg-t-LM were further characterized by 1D 1H and 2D 1H-13C Heteronuclear Multiple Quantum Correlation (HMQC) NMR (Fig. 6A–D). The Cg-t-LM from C. glutamicumΔmptA possessed the same spin systems (Fig. 6C and D) as Cg-LM (Fig. 6A and B) and their anomeric resonances were attributed as follows: δH1C1 5.12/101.2 (I1) to 2,6-Manp, 5.05/105.2 (II1) to t-Manp, 5.00/104.9 (III1) to 2-Manp and 4.92/102.6 (VII1) to 6-Manp units respectively. The intensity of 6-Manp unit resonances is very faint in Cg-LM 1D 1H-NMR spectrum (Fig. 6A) and was found to be much more intense in Cg-t-LM (Fig. 6C), allowing for the observation of a 1H-13C-NMR cross-peak at 4.92/102.6 on the HMQC NMR spectrum (Fig. 6D). Indeed, supporting our earlier glycosyl linkage analysis, integration of the 1D 1H-NMR resonances (2,6-Manp + t-Manp/6-Manp: 7/1 for Cg-LM and 2/1 for Cg-t-LM) indicated a reduced branching degree, approximately 50% for Cg-t-LM, as compared with 78% for Cg-LM. Altogether, the data indicate that Cg-t-LM in C. glutamicumΔmptA occurs possibly as a result of inactivation of a core α(1→6) mannosyltransferase, presumably involved in assembly of the distal portion of Cg-LM, thereby rendering a substrate possessing reduced sites for branching (Fig. 6E).
|
Cg-t-LM
| null |
The Cg-t-LM from C. glutamicumΔmptA possessed the same spin systems (Fig. 6C and D) as Cg-LM (Fig. 6A and B) and their anomeric resonances were attributed as follows: δH1C1 5.12/101.2 (I1) to 2,6-Manp, 5.05/105.2 (II1) to t-Manp, 5.00/104.9 (III1) to 2-Manp and 4.92/102.6 (VII1) to 6-Manp units respectively. The intensity of 6-Manp unit resonances is very faint in Cg-LM 1D 1H-NMR spectrum (Fig. 6A) and was found to be much more intense in Cg-t-LM (Fig. 6C), allowing for the observation of a 1H-13C-NMR cross-peak at 4.92/102.6 on the HMQC NMR spectrum (Fig. 6D). Indeed, supporting our earlier glycosyl linkage analysis, integration of the 1D 1H-NMR resonances (2,6-Manp + t-Manp/6-Manp: 7/1 for Cg-LM and 2/1 for Cg-t-LM) indicated a reduced branching degree, approximately 50% for Cg-t-LM, as compared with 78% for Cg-LM
|
The Cg-t-LM from C. glutamicumΔmptA possessed the same spin systems (Fig. 6C and D) as Cg-LM (Fig. 6A and B) and their anomeric resonances were attributed as follows: δH1C1 5.12/101.2 (I1) to 2,6-Manp, 5.05/105.2 (II1) to t-Manp, 5.00/104.9 (III1) to 2-Manp and 4.92/102.6 (VII1) to 6-Manp units respectively. The intensity of 6-Manp unit resonances is very faint in Cg-LM 1D 1H-NMR spectrum (Fig. 6A) and was found to be much more intense in Cg-t-LM (Fig. 6C), allowing for the observation of a 1H-13C-NMR cross-peak at 4.92/102.6 on the HMQC NMR spectrum (Fig. 6D). Indeed, supporting our earlier glycosyl linkage analysis, integration of the 1D 1H-NMR resonances (2,6-Manp + t-Manp/6-Manp: 7/1 for Cg-LM and 2/1 for Cg-t-LM) indicated a reduced branching degree, approximately 50% for Cg-t-LM, as compared with 78% for Cg-LM
| null |
5.12/101.2 (I1) to 2,6-Manp, 5.05/105.2 (II1) to t-Manp, 5.00/104.9 (III1) to 2-Manp, 4.92/102.6 (VII1) to 6-Manp
| null |
5.12/101.2, 5.05/105.2, 5.00/104.9, 4.92/102.6
| 0.00105
| 17,714,444
|
Mol Microbiol. 2007 Sep; 65(6):1503-1517
|
Mol Microbiol
| 2,007
|
CC BY
|
2021-03-16 23:20:14
|
no
|
PMC2174954
|
Godschalk PC Heikema AP Gilbert M Komagamine T Ang CW Glerum J Brochu D Li J Yuki N Jacobs BC van BA Endtz HP The crucial role of Campylobacter jejuni genes in anti-ganglioside antibody induction in Guillain-Barré syndrome J Clin Invest 2004 114 1659 1665 15578098 10.1172/JCI200415707 Koga M Gilbert M Takahashi M Li J Koike S Hirata K Yuki N Comprehensive analysis of bacterial risk factors for the development of Guillain-Barré syndrome after Campylobacter jejuni enteritis. J Infect Dis 2006 193 547 555 16425134 10.1086/499969 Gilbert M Brisson JR Karwaski MF Michniewicz J Cunningham AM Wu Y Young NM Wakarchuk WW Biosynthesis of ganglioside mimics in Campylobacter jejuni OH4384. Identification of the glycosyltransferase genes, enzymatic synthesis of model compounds, and characterization of nanomole amounts by 600-mhz 1H and 13C NMR analysis J Biol Chem 2000 275 3896 3906 10660542 10.1074/jbc.275.6.3896 van Belkum A van den Braak N Godschalk P Ang W Jacobs B Gilbert M Wakarchuk W Verbrugh H Endtz H A Campylobacter jejuni gene associated with immune-mediated neuropathy Nat Med 2001 7 752 753 11433317 10.1038/89831 Parker CT Horn ST Gilbert M Miller WG Woodward DL Mandrell RE Comparison of Campylobacter jejuni lipooligosaccharide biosynthesis loci from a variety of sources J Clin Microbiol 2005 43 2771 2781 15956396 10.1128/JCM.43.6.2771-2781.2005 Koga M Takahashi M Masuda M Hirata K Yuki N Campylobacter gene polymorphism as a determinant of clinical features of Guillain-Barré syndrome Neurology 2005 65 1376 1381 16162859 10.1212/01.wnl.0000176914.70893.14
|
nanomole amounts
| null |
nanomole amounts by 600-mhz 1H and 13C NMR analysis
|
nanomole amounts by 600-mhz 1H and 13C NMR analysis
|
600-mhz
|
nanomole amounts
|
nanomole amounts by 600-mhz 1H and 13C NMR analysis
|
nanomole amounts
| 0.023428
| 17,919,333
|
BMC Genomics. 2007 Oct 5; 8:359
|
BMC Genomics
| 2,007
|
CC BY
|
2021-01-04 16:49:06
|
no
|
PMC2176056
|
Results and Discussion The cycloaddition of TosMIC 2 to 3,3-di(methylsulfanyl)-1-phenyl-2-propen-1-one 1a was taken as a test case to evaluate the cycloaddition and to arrive at the optimal reaction conditions. The cycloaddition of 2 to 1a took place smoothly in the presence of NaH in THF at rt to furnish [5-[(4-methylphenyl)sulfonyl]-4-(methylsulfanyl)-1H-3-pyrrolyl](phenyl)methanone 3a in 92% yield (Scheme 1 and Table 1). The cycloaddition did not take place when piperidine in THF or K2CO3 in acetone reflux was employed. However, it is to be noted that when Ila and coworkers employed NaH/THF for the cycloaddition of ethyl isocyanoacetate to AKDTA 1a only 20% yield of the desired cycloadduct was obtained. [16] Near quantitative yield (92%) in our reaction indicates higher reactivity of NaH/THF with TosMIC. Two singlets at δ 2.23 and δ 2.42 ppm in the 1H NMR spectrum of 3a assignable for methyls of SMe and tosyl groups respectively served as diagnostic signals. As anticipated the 13C NMR spectrum of 3a displayed fifteen signals, with a diagnostic signal at δ 127.9 ppm assignable to pyrrole C-5.
|
[5-[(4-methylphenyl)sulfonyl]-4-(methylsulfanyl)-1H-3-pyrrolyl](phenyl)methanone
|
O=C(C1=CNC(S(=O)(C2=CC=C(C)C=C2)=O)=C1SC)C3=CC=CC=C3
|
The cycloaddition of TosMIC 2 to 3,3-di(methylsulfanyl)-1-phenyl-2-propen-1-one 1a was taken as a test case to evaluate the cycloaddition and to arrive at the optimal reaction conditions. The cycloaddition of 2 to 1a took place smoothly in the presence of NaH in THF at rt to furnish [5-[(4-methylphenyl)sulfonyl]-4-(methylsulfanyl)-1H-3-pyrrolyl](phenyl)methanone 3a in 92% yield
|
As anticipated the 13C NMR spectrum of 3a displayed fifteen signals, with a diagnostic signal at δ 127.9 ppm assignable to pyrrole C-5
| null |
2.23, 2.42
| null |
127.9
| 0.045717
| 17,903,258
|
Beilstein J Org Chem. 2007 Sep 28; 3:31
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:55
|
no
|
PMC2213660
|
Scheme 6 Alkylation of ketal-ester 12. Surprisingly, alkylation of ketal-ester 12 using NaH in dry DMF proceeded smoothly even at room temperature, however it resulted in an unusual cleavage of ethylene ketal under basic conditions, leading to hydroxy vinylether 13 in 70% yield. The formation of hydroxy vinylether 13 is evident from the spectroscopic data. The presence of a sharp singlet at δH 5.66 (s,1H) in 1H NMR and signals corresponding to vinyl carbons (δc 104.28, 164.39) in 13C NMR, as well as an absorption at 3513 cm-1 in IR spectrum, clearly indicate the presence of a vinylether and a free hydroxyl group in compound 13. Reaction of hydroxy vinylether 13 with acetic anhydride yielded readily the corresponding acetate derivative 14 which further supported the formation of hydroxy vinylether under basic conditions (Scheme 6).
|
hydroxy vinylether
|
C=CO(O)C=C
|
The presence of a sharp singlet at δH 5.66 (s,1H) in 1H NMR and signals corresponding to vinyl carbons (δc 104.28, 164.39) in 13C NMR, as well as an absorption at 3513 cm-1 in IR spectrum, clearly indicate the presence of a vinylether and a free hydroxyl group in compound 13
|
The presence of a sharp singlet at δH 5.66 (s,1H) in 1H NMR and signals corresponding to vinyl carbons (δc 104.28, 164.39) in 13C NMR, as well as an absorption at 3513 cm-1 in IR spectrum, clearly indicate the presence of a vinylether and a free hydroxyl group in compound 13
| null |
5.66 (s,1H)
| null |
104.28, 164.39
| 0.310544
| 18,088,442
|
Beilstein J Org Chem. 2007 Dec 19; 3:49
|
Beilstein J Org Chem
| 2,007
|
CC BY
|
2021-02-20 23:14:55
|
no
|
PMC2225588
|
the resulting residue was purified by chromatography on silica gel (4% MeOH in CH2Cl2 eluant) to yield the tosylate 3 (63 g, 87%) as a colorless viscous oil: 1H NMR (500 MHz, CDCl3) δ 2.43 (s, 3H, ArCH3), 3.35 (s, 3H, OCH3), 3.52 (t, 2H, CH2), 3.50−3.60 (m, 10H, CH2), 3.67 (t, 2H, CH2), 4.14 (t, 2H, CH2), 7.33 (d, 2H, ArH), 7.78 (d, 2H, ArH); 13C NMR (125 MHz, CDCl3) 21.8, 59.1, 68.8, 69.4, 70.6, 70.8, 71.2, 71.6, 71.9, 72.2, 128.1, 130.0, 133.1, 145.0; ESI-MS (m/z) calculated for C16H27O7S [M + H]+ 363.44, found 363.
|
tosylate
|
OS(=O)(C1=CC=C(C)C=C1)=O
|
1H NMR (500 MHz, CDCl3) δ 2.43 (s, 3H, ArCH3), 3.35 (s, 3H, OCH3), 3.52 (t, 2H, CH2), 3.50−3.60 (m, 10H, CH2), 3.67 (t, 2H, CH2), 4.14 (t, 2H, CH2), 7.33 (d, 2H, ArH), 7.78 (d, 2H, ArH)
|
13C NMR (125 MHz, CDCl3) 21.8, 59.1, 68.8, 69.4, 70.6, 70.8, 71.2, 71.6, 71.9, 72.2, 128.1, 130.0, 133.1, 145.0
|
500 MHz, CDCl3
|
2.43 (s, 3H, ArCH3), 3.35 (s, 3H, OCH3), 3.52 (t, 2H, CH2), 3.50−3.60 (m, 10H, CH2), 3.67 (t, 2H, CH2), 4.14 (t, 2H, CH2), 7.33 (d, 2H, ArH), 7.78 (d, 2H, ArH)
|
125 MHz, CDCl3
|
21.8, 59.1, 68.8, 69.4, 70.6, 70.8, 71.2, 71.6, 71.9, 72.2, 128.1, 130.0, 133.1, 145.0
| 0.710702
| 18,274,661
|
Met Based Drugs. 2008 Oct 1; 2008:391418
|
Met Based Drugs
| 2,008
|
CC BY
|
2021-01-05 11:32:13
|
no
|
PMC2225588
|
(80 mL) at reflux under a nitrogen atmosphere for 12 hours. The solvent was then removed under reduced pressure, and the resulting residue was purified by chromatography on silica gel (4% MeOH in CH2Cl2 eluant) to yield 4 (13.40 g, 64%) as a viscous yellow oil: 1H NMR (500 MHz, CDCl3) δ 3.30 (t, 4H, CH2), 3.56 (s, 6H, OCH3), 3.50 (t, 4H, CH2), 3.53 (t, 4H, CH2), 3.58 (t, 4H, CH2), 3.62 ∼ 3.64 (m, 8H, CH2), 3.65 (t, 4H, CH2), 3.74 (t, 4H, CH2); 13C NMR (125 MHz, CDCl3) 21.8, 59.1, 68.8, 69.4, 70.7, 70.8, 71.3, 71.7, 72.0, 73.2, 128.1; ESI-MS (m/z) calculated for C22H39N2O8S2 [M + H]+ 523.69, found 523.
|
4
| null |
1H NMR (500 MHz, CDCl3) δ 3.30 (t, 4H, CH2), 3.56 (s, 6H, OCH3), 3.50 (t, 4H, CH2), 3.53 (t, 4H, CH2), 3.58 (t, 4H, CH2), 3.62 ∼ 3.64 (m, 8H, CH2), 3.65 (t, 4H, CH2), 3.74 (t, 4H, CH2)
|
13C NMR (125 MHz, CDCl3) 21.8, 59.1, 68.8, 69.4, 70.7, 70.8, 71.3, 71.7, 72.0, 73.2, 128.1
|
500 MHz, CDCl3
|
3.30 (t, 4H, CH2), 3.56 (s, 6H, OCH3), 3.50 (t, 4H, CH2), 3.53 (t, 4H, CH2), 3.58 (t, 4H, CH2), 3.62 ∼ 3.64 (m, 8H, CH2), 3.65 (t, 4H, CH2), 3.74 (t, 4H, CH2)
|
125 MHz, CDCl3
|
21.8, 59.1, 68.8, 69.4, 70.7, 70.8, 71.3, 71.7, 72.0, 73.2, 128.1
| 0.886505
| 18,274,661
|
Met Based Drugs. 2008 Oct 1; 2008:391418
|
Met Based Drugs
| 2,008
|
CC BY
|
2021-01-05 11:32:13
|
no
|
PMC2225588
|
green. After 2 hours, the reaction mixture was a deep blue color. Heating and stirring were continued for a total 7 hours after which the solvent was removed under reduced pressure. The resulting residue was dissolved in CH2Cl2 (20 mL). TFA (2 mL) was slowly added, and the solution was stirred for 1 hour. After dilution in CH2Cl2 (100 mL), the mixture was washed 4 times with a large amount of water to remove any residual TFA, dried over Na2SO4, and rotary evaporated. The resulting residue was purified via column chromatography (4% MeOH in CH2Cl2 eluant) to produce 5 (628 mg, 12% yield) as a dark blue solid: UV-vis (CH2Cl2) λmax(log ɛ) 360 (4.66), 502 (2.23), 640 (3.10), 710 (3.99) nm; 1H NMR (500 MHz, CDCl3) δ-1.13 (br s, 2H, NH), 3.32 (s, 24H, –OCH3), 3.40 (t, 16H, CH2), 3.55 ∼ 3.59 (m, 64H, CH2), 3.65 (t, 16H, CH2), 3.99 (t, 16H, CH2), 4.28 (t, 16H, CH2); 13C NMR (125 MHz, CDCl3) 34.76, 59.23, 70.68, 70.72, 70.74, 70.77, 71.11, 72.09, 140.56; MALDI-TOF-MS (m/z) calculated for C88H155N8O32S8 [M + H]+ 2093.72, found 2093.66; calculated for C88H154N8NaO32S8 [M + Na]+ 2115.71, found 2116.48.
|
5
| null |
1H NMR (500 MHz, CDCl3) δ-1.13 (br s, 2H, NH), 3.32 (s, 24H, –OCH3), 3.40 (t, 16H, CH2), 3.55 ∼ 3.59 (m, 64H, CH2), 3.65 (t, 16H, CH2), 3.99 (t, 16H, CH2), 4.28 (t, 16H, CH2)
|
13C NMR (125 MHz, CDCl3) 34.76, 59.23, 70.68, 70.72, 70.74, 70.77, 71.11, 72.09, 140.56
|
500 MHz, CDCl3
|
1.13 (br s, 2H, NH), 3.32 (s, 24H, –OCH3), 3.40 (t, 16H, CH2), 3.55 ∼ 3.59 (m, 64H, CH2), 3.65 (t, 16H, CH2), 3.99 (t, 16H, CH2), 4.28 (t, 16H, CH2)
|
125 MHz, CDCl3
|
34.76, 59.23, 70.68, 70.72, 70.74, 70.77, 71.11, 72.09, 140.56
| 0.595604
| 18,274,661
|
Met Based Drugs. 2008 Oct 1; 2008:391418
|
Met Based Drugs
| 2,008
|
CC BY
|
2021-01-05 11:32:13
|
no
|
PMC2225588
|
2.7. 19,22-bis(1-Methylethoxy)-4,5,9,10,14,15-hexakis{2-{2-[2-(2-methoxyethoxy)ethoxy]-ethoxy}ethylthio}-23H,25H-porphyrazine (6) UV-vis (CH2Cl2) λmax (log ɛ) 350 (4.61), 658 (3.82), 702 (4.35), 744 (sh) nm; 1H NMR (500 MHz, CDCl3) δ-0.20 (br s, 2H, NH), 2.02 (d, 12H, –CHMe3), 3.69 (s, 18H, OCH3), 3.76 ∼ 3.79 (m, 48H, CH2), 3.84 ∼ 3.87 (m, 24H, CH2), 4.02 (t, 4H, CH2), 4.17 (t, 4H, CH2), 4.19 (t, 4H, CH2), 4.39 (t, 4H, CH2), 4.46 (t, 4H, CH2), 4.51 (t, 4H, CH2), 5.49 (sept, 2H, –CHMe2), 7.87 (s, 2H, ArH);13C NMR (125 MHz, CDCl3) 22.3, 22.4, 22.7, 22.9, 29.9, 34.7, 34.8, 34.9, 36.5, 59.2, 70.6, 70.7, 70.8, 71.1, 71.2, 72.1, 72.7, 119.6, 126.5, 138.4, 138.8, 141.9, 150.5; ESI-MS (m/z) calculated for C80H133N8O26S6 [M + H]+ 1815.36, found 1815.70; calculated for C80H132N8NaO32S8 [M + Na]+ 1837.34, found 1837.76.
|
19,22-bis(1-Methylethoxy)-4,5,9,10,14,15-hexakis{2-{2-[2-(2-methoxyethoxy)ethoxy]-ethoxy}ethylthio}-23H,25H-porphyrazine
| null |
1H NMR (500 MHz, CDCl3) δ-0.20 (br s, 2H, NH), 2.02 (d, 12H, –CHMe3), 3.69 (s, 18H, OCH3), 3.76 ∼ 3.79 (m, 48H, CH2), 3.84 ∼ 3.87 (m, 24H, CH2), 4.02 (t, 4H, CH2), 4.17 (t, 4H, CH2), 4.19 (t, 4H, CH2), 4.39 (t, 4H, CH2), 4.46 (t, 4H, CH2), 4.51 (t, 4H, CH2), 5.49 (sept, 2H, –CHMe2), 7.87 (s, 2H, ArH)
|
13C NMR (125 MHz, CDCl3) 22.3, 22.4, 22.7, 22.9, 29.9, 34.7, 34.8, 34.9, 36.5, 59.2, 70.6, 70.7, 70.8, 71.1, 71.2, 72.1, 72.7, 119.6, 126.5, 138.4, 138.8, 141.9, 150.5
|
500 MHz, CDCl3
|
-0.20 (br s, 2H, NH), 2.02 (d, 12H, –CHMe3), 3.69 (s, 18H, OCH3), 3.76 ∼ 3.79 (m, 48H, CH2), 3.84 ∼ 3.87 (m, 24H, CH2), 4.02 (t, 4H, CH2), 4.17 (t, 4H, CH2), 4.19 (t, 4H, CH2), 4.39 (t, 4H, CH2), 4.46 (t, 4H, CH2), 4.51 (t, 4H, CH2), 5.49 (sept, 2H, –CHMe2), 7.87 (s, 2H, ArH)
|
125 MHz, CDCl3
|
22.3, 22.4, 22.7, 22.9, 29.9, 34.7, 34.8, 34.9, 36.5, 59.2, 70.6, 70.7, 70.8, 71.1, 71.2, 72.1, 72.7, 119.6, 126.5, 138.4, 138.8, 141.9, 150.5
| 0.620624
| 18,274,661
|
Met Based Drugs. 2008 Oct 1; 2008:391418
|
Met Based Drugs
| 2,008
|
CC BY
|
2021-01-05 11:32:13
|
no
|
PMC2225981
|
3)2)2N(CH3)). 13C NMR (δ ppm CDCl3, 125 MHz, proton decoupled): 138, 135, 132, 126, 121, 119, 108 [C 5H4 and C 4H(CH2–N(CH3)2)2N(CH3)]; 52 [C5H4–CH–(N(CH3)2)(C4H(CH2–N(CH3)2)2N(CH3)]; 34, 32 [N(CH3)2 and C4H(CH2–N(CH3)2)2N(CH3)].
|
2)2N(CH3)
| null | null |
13C NMR (δ ppm CDCl3, 125 MHz, proton decoupled): 138, 135, 132, 126, 121, 119, 108 [C 5H4 and C 4H(CH2–N(CH3)2)2N(CH3)]; 52 [C5H4–CH–(N(CH3)2)(C4H(CH2–N(CH3)2)2N(CH3)]; 34, 32 [N(CH3)2 and C4H(CH2–N(CH3)2)2N(CH3)]
| null | null |
CDCl3, 125 MHz, proton decoupled
|
138, 135, 132, 126, 121, 119, 108, 52, 34, 32
| 0.273824
| 18,274,663
|
Met Based Drugs. 2008 Oct 1; 2008:754358
|
Met Based Drugs
| 2,008
|
CC BY
|
2021-01-05 11:32:14
|
no
|
PMC2225981
|
3)2)]. 13C NMR (δ ppm CDCl3, 125 MHz, proton decoupled): 146, 138, 136, 132, 131, 129, 127, 124, 120 [(C 6H4 CH2N(CH3)2) and (C 5H4)]; 61 [C5H4–CH–(N(CH3)2 (C6H4CH2N(CH3)2))]; 60 [(C6H4 CH2N(CH3)2)]; 42 [C5H4–CH–(N(CH3)2(C6H4CH2N(CH3)2))].
|
(C 5H4) and (C 6H4 CH2N(CH3)2)
| null | null |
146, 138, 136, 132, 131, 129, 127, 124, 120 [(C 6H4 CH2N(CH3)2) and (C 5H4)]; 61 [C5H4–CH–(N(CH3)2 (C6H4CH2N(CH3)2)]; 60 [(C6H4 CH2N(CH3)2)]; 42 [C5H4–CH–(N(CH3)2(C6H4CH2N(CH3)2)]
| null | null |
CDCl3, 125 MHz, proton decoupled
|
146, 138, 136, 132, 131, 129, 127, 124, 120 [(C 6H4 CH2N(CH3)2) and (C 5H4)]; 61 [C5H4–CH–(N(CH3)2 (C6H4CH2N(CH3)2)]; 60 [(C6H4 CH2N(CH3)2)]; 42 [C5H4–CH–(N(CH3)2(C6H4CH2N(CH3)2)]
| 0.001789
| 18,274,663
|
Met Based Drugs. 2008 Oct 1; 2008:754358
|
Met Based Drugs
| 2,008
|
CC BY
|
2021-01-05 11:32:14
|
no
|
PMC2248282
|
O-(2,4-Dimethoxybenzyl)hydroxylamine (11b). N-(2,4-dimethoxybenzyloxy)phthalamide 10b (1.83 g, 5,84 mmol) was stirred as a suspension in 60 mL of refluxing ethanol. N-methylhydrazine (0.34 mL, 6.4 mmol) was added, and the mixture was stirred at reflux for 1 h. The solution was concentrated to remove the ethanol. Ether (60 mL) was added, and the reaction mixture was allowed to stand at room temperature for 30 min. The resulting solid was filtered. The organic solution was concentrated to give 1.37 g (∼quant.) of 11b slightly contaminated with some phtalamide. Rf 0.69 (10% MeOH/CHCl3). 1H NMR (500 MHz, CDCI3): δ=3.77 (3H, s, OCH3), 3.78 (3H, s, OCH3), 4.64 (2H, s, CH2), 5.41 (2H, bs, NH2), 6.43–6.44 (2H, m, Ar-H), 7.19–7.22 ppm (1H, m, Ar-H). (4R,5R)-N-(2,4-dimethoxybenzyloxy)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolane-4-carboxamide (4b). Trimethylaluminum (2.0m solution in hexanes; 3.5 mL, 7 mmol) was added dropwise over 15 min to a stirred solution of 11b (1.06 g, 5.84 mmol) and isopropilidene-erythronolactone (923 mg, 5.84 mmol) in CH2Cl2 (50 mL) cooled at −78°C. The clear yellowish solution was warmed to room temperature and stirred overnight. The clear solution was added cautiously in small portions to a vigorously stirred saturated aqueous NaHCO3 (100 mL, gas evolution occurs) and the mixture was stirred for 15 min. The aluminium salts formed were removed by filtration and washed with methanol and then with CH2Cl2. The organic layer of the biphasic filtrate was separated, the aqueous phase extracted with CH2Cl2 (3×20 mL) and the combined organic extracts were concentrated in vacuo. The residue was dissolved in a minimum amount of a warm mixture of hexane 20% in EtOAc and recrystallized upon cooling to 4°C. White crystals, 783 mg, 40%. Rf 0.13 (50% EtOAc/hexane). 1H NMR (500 MHz, CDCl3): δ=1.34 (3H, s, C(CH3)2), 1.41 (3H, s, C(CH3)2), 3.26–3.29 (1H, m, OH), 3.65–3.69 (1H, m, CHHOH), 3.77–3.79 (1H, m, CHHOH), 3.81 (3H, s, OCH3), 3.83 (3H, s, OCH3), 4.51–4.55 (1H, m, CHCH2OH), 4.66 (1H, d, J=7.5 Hz, COCH), 4.94 (2H, m, ArCH2), 6.47–6.49 (2H, m, Ar-H), 7.25 (1H, d, J=7.3 Hz, Ar-H), 8.91 ppm (1H, s, NH). 13C NMR (125 MHz, CDCl3): δ=24.3 (C(CH3)2), 26.6 (C(CH3)2), 55.46 (OCH3), 55.58 (OCH3), 61.4 (CHCH2OH), 73.6 (ArCH2), 76.5 (CHCH2OH), 77.6 (COCHCH), 98.6 (CH-Ar), 104.2 (CH-Ar), 110.2 (C(CH3)2), 115.5 (C-Ar), 132.9 (CH-Ar), 159.5 (CH3OC-Ar), 161.9 (CH3OC-Ar), 167.1 ppm (NHCOCH); LRMS (ES+): m/z (%) 342.5 (30) [M+H]+, 364.3 (100) [M+Na]+.
|
O-(2,4-Dimethoxybenzyl)hydroxylamine
|
NOCC1=CC=C(OC)C=C1OC
|
1H NMR (500 MHz, CDCI3): δ=3.77 (3H, s, OCH3), 3.78 (3H, s, OCH3), 4.64 (2H, s, CH2), 5.41 (2H, bs, NH2), 6.43–6.44 (2H, m, Ar-H), 7.19–7.22 ppm (1H, m, Ar-H)
|
13C NMR (125 MHz, CDCl3): δ=24.3 (C(CH3)2), 26.6 (C(CH3)2), 55.46 (OCH3), 55.58 (OCH3), 61.4 (CHCH2OH), 73.6 (ArCH2), 76.5 (CHCH2OH), 77.6 (COCHCH), 98.6 (CH-Ar), 104.2 (CH-Ar), 110.2 (C(CH3)2), 115.5 (C-Ar), 132.9 (CH-Ar), 159.5 (CH3OC-Ar), 161.9 (CH3OC-Ar), 167.1 ppm (NHCOCH)
|
500 MHz, CDCI3
|
3.77 (3H, s, OCH3), 3.78 (3H, s, OCH3), 4.64 (2H, s, CH2), 5.41 (2H, bs, NH2), 6.43–6.44 (2H, m, Ar-H), 7.19–7.22 (1H, m, Ar-H)
|
125 MHz, CDCl3
|
24.3, 26.6, 55.46, 55.58, 61.4, 73.6, 76.5, 77.6, 98.6, 104.2, 110.2, 115.5, 132.9, 159.5, 161.9, 167.1
| 0.252276
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-(2-hydroxy-ethyl) ester (13). Pivaloyl chloride (3.2 mL, 26 mmol) was added to a stirred solution of 2-mercaptoethanol (1.8 mL, 26 mmol) and triethylamine (3.6 mL, 26 mmol) in CH2Cl2, cooled at −78°C. The mixture was stirred at −78°C for 1 h, then allowed to warm to room temperature and stirred further for 1 h. Water (30 mL) was added, the organic layer was separated, and the aqueous phase extracted with CH2Cl2 (3×20 mL). The combined organic extracts were dried over Na2SO4 and concentrated in vacuo. The oily residue was purified by flash column chromatography (SiO2, hexane/EtOAc 90%→75%) to afford the title compound as colourless oil, 4.02 g, 95%. Rf 0.44 in (70% EtOAc/hexane). 1H NMR (500 MHz, CDCl3): δ=1.23 (9H, s, C(CH3)3), 2.62 (1H, bs, OH), 3.04 (2H, t, J=6.1 Hz SCH2), 3.72 ppm (2H, t, J=6.1 Hz, OCH2). 13C NMR (125 MHz, CDCl3): δ=27.8 (CH3), 31.9 (SCH2), 47.0 (CMe3), 63.2 (OCH2), 207.7 ppm (SCO).
|
2,2-Dimethyl-thiopropionic acid S-(2-hydroxy-ethyl) ester
|
CC(C)(C)C(SCCO)=O
|
1H NMR (500 MHz, CDCl3): δ=1.23 (9H, s, C(CH3)3), 2.62 (1H, bs, OH), 3.04 (2H, t, J=6.1 Hz SCH2), 3.72 ppm (2H, t, J=6.1, OCH2)
|
13C NMR (125 MHz, CDCl3): δ=27.8 (CH3), 31.9 (SCH2), 47.0 (CMe3), 63.2 (OCH2), 207.7 ppm (SCO)
|
500 MHz, CDCl3
|
1.23 (9H, s, C(CH3)3), 2.62 (1H, bs, OH), 3.04 (2H, t, J=6.1 Hz SCH2), 3.72 ppm (2H, t, J=6.1, OCH2)
|
125 MHz, CDCl3
|
27.8, 31.9, 47.0, 63.2, 207.7
| 0.416134
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-[2-(chloro-phenoxy-phosphoryloxy)-ethyl] ester (5a). Dichloro phenyl phosphonate (1.06 g, 5 mmol) was added dropwise into a cooled solution (−78°C) of 13 (0.81 g, 5 mmol) and TEA (0.70 mL, 5 mmol) in THF (20 mL). The reaction was left to warm to room temperature and stirred overnight. The white precipitate was filtered off and the solution was concentrated under reduced pressure, the crude residue (yellowish oil) was used for the next step without further purification. Rf 0.66 in (50% EtOAc/hexane). 1H NMR (500 MHz, CDCl3): δ=1.25 (9H, s, C(CH3)3), 3.24 (2H, t, J=6.4 Hz, CH2CH2S), 4.34–4.41 (2H, m, CH2CH2OP), 7.25–7.28 (3H, m, Ph-H), 7.39 ppm (2H, t, J=7.9 Hz, Ph-H). 13C NMR (125 MHz, CDCl3): δ=27.3 (C(CH3)3), 28.2, 28.1 (CH2S), 46.5 (C(CH3)3), 68.2 (d, J=7.20 Hz, CH2O), 120.3 (d, J=5.3 Hz, orto-CH-Ar), 126.3 (meta-CH-Ar), 130.0 (para-CH-Ar), 149.7 (d, J=8.9 Hz, C-Ar), 205.6 ppm (SCO). 31P NMR (202 MHz, CDCl3): δ=−0.66 ppm.
|
2,2-Dimethyl-thiopropionic acid S-[2-(chloro-phenoxy-phosphoryloxy)-ethyl] ester
|
CC(C)(C)C(SCCOP(OC1=CC=CC=C1)(Cl)=O)=O
|
1H NMR (500 MHz, CDCl3): δ=1.25 (9H, s, C(CH3)3), 3.24 (2H, t, J=6.4 Hz, CH2CH2S), 4.34–4.41 (2H, m, CH2CH2OP), 7.25–7.28 (3H, m, Ph-H), 7.39 ppm (2H, t, J=7.9 Hz, Ph-H)
|
13C NMR (125 MHz, CDCl3): δ=27.3 (C(CH3)3), 28.2, 28.1 (CH2S), 46.5 (C(CH3)3), 68.2 (d, J=7.20 Hz, CH2O), 120.3 (d, J=5.3 Hz, orto-CH-Ar), 126.3 (meta-CH-Ar), 130.0 (para-CH-Ar), 149.7 (d, J=8.9 Hz, C-Ar), 205.6 ppm (SCO)
|
500 MHz, CDCl3
|
1.25 (9H, s, C(CH3)3), 3.24 (2H, t, J=6.4 Hz, CH2CH2S), 4.34–4.41 (2H, m, CH2CH2OP), 7.25–7.28 (3H, m, Ph-H), 7.39 ppm (2H, t, J=7.9 Hz, Ph-H)
|
125 MHz, CDCl3
|
27.3, 28.2, 28.1, 46.5, 68.2, 120.3, 126.3, 130.0, 149.7, 205.6
| 0.664738
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-(2-{[5-(4-methoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphoryloxy}-ethyl) ester (26a). Compound 4a (100 mg, 0.32 mmol) was dissolved in dry DCM (4.5 mL) and was added into a solution of 13 (151 mg, 0.45 mmol) in dry DCM (2.5 mL). The mixture was cooled to −78°C and followed by the addition of N-methylimidazole (0.076 mL, 0.96 mmol) with a syringe. The reaction was kept 15 min at −78°C and the 3 h at room temperature. The reaction was quenched adding methanol (2 mL). The residue was extracted with DCM and washed with HCl 0.1m (3×10 mL). The organic layer was dried over MgSO4, filtered, evaporated to dryness, and purified twice by flash chromatography. Eluting the first column with hexane/EtOAc 95%→60%. Eluting the second column with Chloroform 100%→Chloroform/MeOH 99.5%. The desired compound was obtained as colourless oil, 134 mg, 68%. 1H NMR (500 MHz, CDCl3): δ=1.14, 1.15 (9H, 2 s, C(CH3)3), 1.25, 1.26 (3H, 2 s, C(CH3)2), 1.34, 1,36 (3H, 2 s, C(CH3)2), 3.06 (2H, d, J=6.7 Hz, CH2S), 3.73 (3H, s, OCH3), 4.06–4.16 (3H, m, CHHOP+OCH2CH2S), 4.42–4.56 (3H, m, CHCH+CHCH+CHCHHOP), 4.74–4.83 (2H, m, ArCH2), 6.82 (2H, dd, J1=1.6 Hz, J2=8.7 Hz, Ar-H), 7.09 (1H, t, J=7.3 Hz, Ph-H), 7.15–7.17 (2H, m, Ar-H), 7.23–7.29 (4H, m, Ph-H), 8.70, 8.75 ppm (1H, 2 s, NH). 13C NMR (125 MHz, CDCl3): δ=24.5, 25.5 (CCH3), 26.5, 26.6 (CCH3), 27.0, 27.3 (C(CH3)3), 28.4, 28.5 (CH2S), 55.3 (OCH3), 66.66, 66.69, 66.71, 66.76 (CHCH2OP + POCH2CH2S), 74.9, 75.0 (CHCH2OP), 75.8, 75.9 (COCHCH), 78.2 (ArCH2O), 110.7 (C(CH3)2), 113.9, 114.0 (Ph-CH), 120.1, 120.2 (Ph-CH), 125.2 (Ar-C), 126.78, 126.86 (Ph-C), 129.70 (Ar-CH), 131.1 (Ar-CH), 150.44, 150.50 (Ph-C), 160.1 (Ar-C), 165.5 (HNCO), 205.7 ppm (SCO). 31P NMR (202 MHz, CDCl3): δ=−6.94, −7.10 ppm; LRMS (ES+): m/z (%) 634.5 (100) [M+Na]+, 612.5 (50) [M+H]+.
|
2,2-Dimethyl-thiopropionic acid S-(2-{[5-(4-methoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphoryloxy}-ethyl) ester
|
CC(C)(C)C(OCCOP(OC1=CC=CC=C1)(OCC2OC(C)(C)O[C@@H]2C(NOCC3=CC=C(OC)C=C3)=O)=O)=S
|
1H NMR (500 MHz, CDCl3): δ=1.14, 1.15 (9H, 2 s, C(CH3)3), 1.25, 1.26 (3H, 2 s, C(CH3)2), 1.34, 1,36 (3H, 2 s, C(CH3)2), 3.06 (2H, d, J=6.7 Hz, CH2S), 3.73 (3H, s, OCH3), 4.06–4.16 (3H, m, CHHOP+OCH2CH2S), 4.42–4.56 (3H, m, CHCH+CHCH+CHCHHOP), 4.74–4.83 (2H, m, ArCH2), 6.82 (2H, dd, J1=1.6 Hz, J2=8.7 Hz, Ar-H), 7.09 (1H, t, J=7.3 Hz, Ph-H), 7.15–7.17 (2H, m, Ar-H), 7.23–7.29 (4H, m, Ph-H), 8.70, 8.75 ppm (1H, 2 s, NH)
|
13C NMR (125 MHz, CDCl3): δ=24.5, 25.5 (CCH3), 26.5, 26.6 (CCH3), 27.0, 27.3 (C(CH3)3), 28.4, 28.5 (CH2S), 55.3 (OCH3), 66.66, 66.69, 66.71, 66.76 (CHCH2OP + POCH2CH2S), 74.9, 75.0 (CHCH2OP), 75.8, 75.9 (COCHCH), 78.2 (ArCH2O), 110.7 (C(CH3)2), 113.9, 114.0 (Ph-CH), 120.1, 120.2 (Ph-CH), 125.2 (Ar-C), 126.78, 126.86 (Ph-C), 129.70 (Ar-CH), 131.1 (Ar-CH), 150.44, 150.50 (Ph-C), 160.1 (Ar-C), 165.5 (HNCO), 205.7 ppm (SCO)
|
500 MHz, CDCl3
|
1.14, 1.15 (9H, 2 s, C(CH3)3), 1.25, 1.26 (3H, 2 s, C(CH3)2), 1.34, 1,36 (3H, 2 s, C(CH3)2), 3.06 (2H, d, J=6.7 Hz, CH2S), 3.73 (3H, s, OCH3), 4.06–4.16 (3H, m, CHHOP+OCH2CH2S), 4.42–4.56 (3H, m, CHCH+CHCH+CHCHHOP), 4.74–4.83 (2H, m, ArCH2), 6.82 (2H, dd, J1=1.6 Hz, J2=8.7 Hz, Ar-H), 7.09 (1H, t, J=7.3 Hz, Ph-H), 7.15–7.17 (2H, m, Ar-H), 7.23–7.29 (4H, m, Ph-H), 8.70, 8.75 ppm (1H, 2 s, NH)
|
125 MHz, CDCl3
|
24.5, 25.5, 26.5, 26.6, 27.0, 27.3, 28.4, 28.5, 55.3, 66.66, 66.69, 66.71, 66.76, 74.9, 75.0, 75.8, 75.9, 78.2, 110.7, 113.9, 114.0, 120.1, 120.2, 125.2, 126.78, 126.86, 129.70, 131.1, 150.44, 150.50, 160.1, 165.5, 205.7
| 0.734953
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-(2-{[5-(2,4-dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphoryloxy}-ethyl) ester (26b). NMI (0.07 mL, 0.87 mmol) was added into a cooled solution (−78°C) of 4b (100 mg, 0.29 mmol) and 13 (140 mg, 0.41 mmol) in anhydrous DCM (7 mL). The reaction was stirred for 30 min at −78°C, then 1 h at room temperature. The solvent was removed under reduced pressure; the crude residue was dissolved in DCM (10 mL), washed with HCl 0.1 N (3×10 mL), dried over Na2SO4, and concentrated in vacuo. The crude oil was purified by chromatography (SiO2) eluting with EtOAc (35%→50%) in hexane. The title compound was isolated as colourless oil, 147 mg, 79%. 1H NMR (500 MHz, CDCl3): δ=1.14, 1.145 (9H, 2 s, C(CH3)3), 1.26, 1.27 (3H, 2 s, C(CH3)2), 1.37, 1.39 (3H, 2 s, C(CH3)2), 3.05 (2H, t, J=6.7 Hz, CH2S), 3.73 (3H, s, OCH3), 3.75 (3H, s, OCH3), 4.10–4.15 (3H, m, OCH2CH2S + CHCHHOP), 4.43–4.57 (3H, m, COCH + CHCHCH2OP + CHCHHOP), 4.80–4.87 (2, m, ArCH2), 6.39–6.43 (2H, m, Ph-H), 7.13–7.26 (5H, m, Ph-H + Ar-H), 8.80, 8.83 ppm (1H, 2 s, NH). 13C NMR (125 MHz, CDCl3): δ=24.5 (C(CH3)2), 26.68, 26.71 (C(CH3)2), 27.3 (C(CH3)3), 28.43, 28.48 (CH2S), 55.4, 55.5 (OCH3), 66.6, 66.7, 66.8, 66.9 (CHCH2OP + POCH2CH2S), 73.5, 73.6 (ArCH2), 74.95, 74.98 (CHCH2OP), 75.89, 75.94 (COCHCH), 98.6 (Ar-CH), 104.1 (Ar-CH), 110.4 (C(CH3)2), 120.1, 120.2 (Ph-CH), 125.1 (Ph-CH), 129.7 (Ph-CH), 132.9 ppm (Ar-CH), 31P NMR (202 MHz, CDCl3): δ=−6.93, −7.09 ppm; LRMS (ES+): m/z (%) 664.5 (100) [M+Na]+, 642.5 (40) [M+H]+.
|
2,2-Dimethyl-thiopropionic acid S-(2-{[5-(2,4-dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphoryloxy}-ethyl) ester
|
CC(C)(C)C(OCCOP(OC1=CC=CC=C1)(OCC2OC(C)(C)O[C@@H]2C(NOCC3=CC=C(OC)C=C3OC)=O)=O)=S
|
1H NMR (500 MHz, CDCl3): δ=1.14, 1.145 (9H, 2 s, C(CH3)3), 1.26, 1.27 (3H, 2 s, C(CH3)2), 1.37, 1.39 (3H, 2 s, C(CH3)2), 3.05 (2H, t, J=6.7 Hz, CH2S), 3.73 (3H, s, OCH3), 3.75 (3H, s, OCH3), 4.10–4.15 (3H, m, OCH2CH2S + CHCHHOP), 4.43–4.57 (3H, m, COCH + CHCHCH2OP + CHCHHOP), 4.80–4.87 (2, m, ArCH2), 6.39–6.43 (2H, m, Ph-H), 7.13–7.26 (5H, m, Ph-H + Ar-H), 8.80, 8.83 ppm (1H, 2 s, NH)
|
13C NMR (125 MHz, CDCl3): δ=24.5 (C(CH3)2), 26.68, 26.71 (C(CH3)2), 27.3 (C(CH3)3), 28.43, 28.48 (CH2S), 55.4, 55.5 (OCH3), 66.6, 66.7, 66.8, 66.9 (CHCH2OP + POCH2CH2S), 73.5, 73.6 (ArCH2), 74.95, 74.98 (CHCH2OP), 75.89, 75.94 (COCHCH), 98.6 (Ar-CH), 104.1 (Ar-CH), 110.4 (C(CH3)2), 120.1, 120.2 (Ph-CH), 125.1 (Ph-CH), 129.7 (Ph-CH), 132.9 ppm (Ar-CH), 31P NMR (202 MHz, CDCl3): δ=−6.93, −7.09 ppm
|
500 MHz, CDCl3
|
1.14, 1.145 (9H, 2 s, C(CH3)3), 1.26, 1.27 (3H, 2 s, C(CH3)2), 1.37, 1.39 (3H, 2 s, C(CH3)2), 3.05 (2H, t, J=6.7 Hz, CH2S), 3.73 (3H, s, OCH3), 3.75 (3H, s, OCH3), 4.10–4.15 (3H, m, OCH2CH2S + CHCHHOP), 4.43–4.57 (3H, m, COCH + CHCHCH2OP + CHCHHOP), 4.80–4.87 (2, m, ArCH2), 6.39–6.43 (2H, m, Ph-H), 7.13–7.26 (5H, m, Ph-H + Ar-H), 8.80, 8.83 ppm (1H, 2 s, NH)
|
125 MHz, CDCl3
|
24.5, 26.68, 26.71, 27.3, 28.43, 28.48, 55.4, 55.5, 66.6, 66.7, 66.8, 66.9, 73.5, 73.6, 74.95, 74.98, 75.89, 75.94, 98.6, 104.1, 110.4, 120.1, 120.2, 125.1, 129.7, 132.9
| 0.267631
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-(2-{[5-(2,4-dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphoryloxy}-ethyl) ester (3d). 26b (115 mg, 0.18 mmol) was dissolved in a solution of 5% TFA in DCM (2 mL) and stirred at room temperature. After 15 min the colourless solution became deep purple and the starting material had completely reacted. The solution was concentrated under reduced pressure. The residue was taken in ether (5 mL), the white precipitate was filtered off, and the filtrate was concentrated in vacuo. The residue was redissolved in MeOH (5 mL), and the second precipitate formed was filtered. The filtrate was purified by chromatography eluting the silica with MeOH 0%→10% in DCM. The mix SATE prodrug 3d was obtained as colourless oil, 56 mg (63%). 1H NMR (500 MHz, CDCl3): δ=1.15 (9H, s, C(CH3)3), 1.28 (3H, s, C(CH3)2),1.44, 1.45 (3H, 2 s, C(CH3)2), 3.07 (2H, dd, J=12.4, 6.4 Hz, CH2S), 4.09–4.22 (3H, m, CH2CH2S + CHCHHOP), 4.29–4.34 (1H, m, CHHOP), 4.52 (1H, bs, CHCH2OP), 4.66 (1H, d, J=7.6 Hz, COCHCH), 7.09–7.16 (3H, m, Ph-H), 7.27 (2H, t, J=7.9 Hz, Ph-H), 9.00, 9.09 ppm (1H, 2 s, NH). 13C NMR (125 MHz, CDCl3): δ=24.55, 24.57 (C(CH3)2), 26.63, 26.68 (C(CH3)2), 27.3 (C(CH3)3), 28.33, 28.41 (CH2S), 66.53, 66.58, 66.69, 66.74, 66.87, 66.92, 67.13, 67.17 (CH2OP + CH2CH2S), 74.68, 74.79 (CHCH2OP), 75.75, 75.80 (COCHCH), 111.5 (C(CH3)2), 120.10, 120.17 (Ph-CH), 125.36, 125.41 (Ph-CH), 129.79 (Ph-CH), 150.4 (Ph-C), 165.2 (HNCOCH)), 205.9 ppm (SCO); 31P NMR (202 MHz, CDCl3): δ=−7.03, −7.06 ppm. LRMS (ES+): m/z 514.2 (100) [M+Na]+; HRMS (ES+) required for C20H31N1O9PS 492.1452, found 492.1429. LC-M: Rt 8.3 min; m/z 492; purity 80% by UV and TIC traces.
|
2,2-Dimethyl-thiopropionic acid S-(2-{[5-(2,4-dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphoryloxy}-ethyl) ester
|
CC(C)(C)C(OCCOP(OC1=CC=CC=C1)(OCC2OC(C)(C)O[C@@H]2C(NOCC3=CC=C(OC)C=C3OC)=O)=O)=S
|
1H NMR (500 MHz, CDCl3): δ=1.15 (9H, s, C(CH3)3), 1.28 (3H, s, C(CH3)2),1.44, 1.45 (3H, 2 s, C(CH3)2), 3.07 (2H, dd, J=12.4, 6.4 Hz, CH2S), 4.09–4.22 (3H, m, CH2CH2S + CHCHHOP), 4.29–4.34 (1H, m, CHHOP), 4.52 (1H, bs, CHCH2OP), 4.66 (1H, d, J=7.6 Hz, COCHCH), 7.09–7.16 (3H, m, Ph-H), 7.27 (2H, t, J=7.9 Hz, Ph-H), 9.00, 9.09 ppm (1H, 2 s, NH)
|
13C NMR (125 MHz, CDCl3): δ=24.55, 24.57 (C(CH3)2), 26.63, 26.68 (C(CH3)2), 27.3 (C(CH3)3), 28.33, 28.41 (CH2S), 66.53, 66.58, 66.69, 66.74, 66.87, 66.92, 67.13, 67.17 (CH2OP + CH2CH2S), 74.68, 74.79 (CHCH2OP), 75.75, 75.80 (COCHCH), 111.5 (C(CH3)2), 120.10, 120.17 (Ph-CH), 125.36, 125.41 (Ph-CH), 129.79 (Ph-CH), 150.4 (Ph-C), 165.2 (HNCOCH)), 205.9 ppm (SCO)
|
500 MHz, CDCl3
|
1.15 (9H, s, C(CH3)3), 1.28 (3H, s, C(CH3)2),1.44, 1.45 (3H, 2 s, C(CH3)2), 3.07 (2H, dd, J=12.4, 6.4 Hz, CH2S), 4.09–4.22 (3H, m, CH2CH2S + CHCHHOP), 4.29–4.34 (1H, m, CHHOP), 4.52 (1H, bs, CHCH2OP), 4.66 (1H, d, J=7.6 Hz, COCHCH), 7.09–7.16 (3H, m, Ph-H), 7.27 (2H, t, J=7.9 Hz, Ph-H), 9.00, 9.09 ppm (1H, 2 s, NH)
|
125 MHz, CDCl3
|
24.55, 24.57, 26.63, 26.68, 27.3, 28.33, 28.41, 66.53, 66.58, 66.69, 66.74, 66.87, 66.92, 67.13, 67.17, 74.68, 74.79, 75.75, 75.80, 111.5, 120.10, 120.17, 125.36, 125.41, 129.79, 150.4, 165.2, 205.9
| 0.661252
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-(2-{diisopropylamino-[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-phosphanyloxy}-ethyl) ester (6a). A solution of S-pivaloyl thioethanol 13 (1.62 g, 10 mmol) and triethylamine (3.06 mL, 22 mmol) in THF (35 mL) was added dropwise over 1.5 h at −78°C into a solution of diisopropylamino dichloro phosphine 22 (1.01 g, 9 mmol) in THF (35 mL). The white suspension was stirred for 2 h at room temperature, and then it was filtered to remove the triethylamine hydrochloride salt. The filtrate was concentrated under reduced pressure affording a white syrup. The residue was further purified by treating it with hexane and filtering the white precipitate formed. The title compound was used as crude for the next step. 1H NMR (500 MHz, CDCl3): δ=1.09, 1.10 (12H, 2 s, 2×CH(CH3)2), 1.16, 1.17 (18H, 2 s, 2×C(CH3)3), 3.00–3.06 (4H, m, 2×CH2S), 3.46–3.71 ppm (6H, m, 2×(CH2O) + 2×(CH(CH3)2); 31P NMR (202 MHz, CDCl3): δ=147.2 ppm. 2,2-dimethyl-thiopropionic acid S-(2-{[5-(2,4-dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-phosphoryloxy}-ethyl) ester (27). Tetrazole (3.3 mL of solution 0.45m in CH3CN) was added to a suspension of 6a (340 mg, 0.75 mmol) and 4b (171 mg, 0.50 mmol) in THF. After the addition the mixture became a clear solution and was stirred for 1.5 h at room temperature. The flask was cooled to −78°C with a dry-ice/acetone bath and followed by the addition of a solution of tert-butyl hydroperoxide in water (0.15 mL, 1.20 mmol). The reaction was kept at −78°C for 15 min, then warmed to room temperature and stirred for a further 30 min. A solution of Na2SO3 10% in water (1.2 mL) was added to destroy the excess of peroxide. The solution was diluted with DCM (20 mL), washed with water (10 mL), and dried over Na2SO4. The organic solution was concentrated under reduced pressure to afford a colourless oil which was purified by chromatography. SiO2 eluted with hexane 60%→30% in EtOAc. Compound 27 was obtained as viscous oil, 229 mg, 64%. 1H NMR (500 MHz, CDCl3): δ=1.16 (18H, s, 2×C(CH3)3), 1.28 (3H, s, C(CH3)2), 1.41 (3H, s, C(CH3)2), 3.07 (4H, t, J=6.6 Hz, 2×CH2S), 3.75 (3H, s, OCH3), 3.77 (3H, s, OCH3), 3.96–4.07 (5H, m, 2×POCH2CH2S+ CHCHHOP), 4.34–4.37 (1H, m, CHHOP), 4.55 (2H, bs, CHCHCH2OP), 4.85 (2H, AB syst., J=11.0 Hz, ArCH2), 6.40–6.43 (2H, m, Ar-H), 7.20 (1H, s, Ar-H), 8.83 ppm (1H, bs, NH). 13C NMR (125 MHz, CDCl3): δ=24.6 (C(CH3)2), 26.7 (C(CH3)2), 27.3 (C(CH3)3), 28.5, 28.55 (CH2S), 46.5 (C(CH3)3), 55.4, 55.6 (OCH3), 66.1, 66.2, 66.3 (POCH2 + CHCH2OP), 73.5 (ArCH2), 75.0 (CHCH2OP), 75.96, 76.02 (COCH), 98.6 (Ar-CH). 104.2 (Ar-CH), 110.7 (C(CH3)2), 115.7 (Ar-CH), 132.9 (Ar-C), 159.4 (Ar-C), 161.8 (Ar-C), 165.2 (HNCO), 205.7 ppm (SCO). 31P NMR (202 MHz, CDCl3): δ=−2.05 ppm; LRMS (ES+): m/z (%) 710 (15) [M+H]+, 727 (100) [M+H2O]+, 732 (90) [M+Na]+.
|
2,2-Dimethyl-thiopropionic acid S-(2-{diisopropylamino-[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-phosphanyloxy}-ethyl) ester
|
CC(C)(C)C(OCCO[P@](N(C(C)C)C(C)C)OCCSC(C(C)(C)C)=O)=S
|
1H NMR (500 MHz, CDCl3): δ=1.09, 1.10 (12H, 2 s, 2×CH(CH3)2), 1.16, 1.17 (18H, 2 s, 2×C(CH3)3), 3.00–3.06 (4H, m, 2×CH2S), 3.46–3.71 ppm (6H, m, 2×(CH2O) + 2×(CH(CH3)2)
|
13C NMR (125 MHz, CDCl3): δ=24.6 (C(CH3)2), 26.7 (C(CH3)2), 27.3 (C(CH3)3), 28.5, 28.55 (CH2S), 46.5 (C(CH3)3), 55.4, 55.6 (OCH3), 66.1, 66.2, 66.3 (POCH2 + CHCH2OP), 73.5 (ArCH2), 75.0 (CHCH2OP), 75.96, 76.02 (COCH), 98.6 (Ar-CH). 104.2 (Ar-CH), 110.7 (C(CH3)2), 115.7 (Ar-CH), 132.9 (Ar-C), 159.4 (Ar-C), 161.8 (Ar-C), 165.2 (HNCO), 205.7 ppm (SCO)
|
500 MHz, CDCl3
|
1.09, 1.10 (12H, 2 s, 2×CH(CH3)2), 1.16, 1.17 (18H, 2 s, 2×C(CH3)3), 3.00–3.06 (4H, m, 2×CH2S), 3.46–3.71 (6H, m, 2×(CH2O) + 2×(CH(CH3)2)
|
125 MHz, CDCl3
|
24.6, 26.7, 27.3, 28.5, 28.55, 46.5, 55.4, 55.6, 66.1, 66.2, 66.3, 73.5, 75.0, 75.96, 76.02, 98.6, 104.2, 110.7, 115.7, 132.9, 159.4, 161.8, 165.2, 205.7
| 0.191137
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-thiopropionic acid S-{2-[[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-(5-hydroxycarbamoyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phosphoryloxy]-ethyl} ester (3a). TFA (0.040 mL) was added into a solution of 27 (157 mg, 0.22 mmol) in DCM (4 mL). The reaction was stirred at room temperature until the complete disappearance of the starting material was observed by TLC (5% MeOH in DCM). The mixture was diluted with MeOH (5 mL) and the white precipitate was filtered off. The filtrate was concentrated in vacuo and purified by chromatography. SiO2 eluted with MeOH 0%→4% in DCM. The bisSATE phosphate diester prodrug 3a was obtained as colourless oil, 91 mg, 73%. 1H NMR (500 MHz, CDCl3): δ=1.17, 1.17 (18H, 2 s, C(CH3)3), 1.30 (3H, s, C(CH3)2), 1.47 (3H, s, C(CH3)2), 3.06 (2H, t, J=6.8 Hz, CH2S), 3.09 (2H, t, J=6.7 Hz, CH2S), 4.00–4.05 (2H, m, CHCH2OP), 4.06–4.20 (4H, m, 2×POCH2CHS), 4.49–4.53 (1H, m, CHCH2OP), 4.68 (1H, d, J=7.5 Hz, COCH), 7.72 (1H, bs, OH), 8.90 ppm (1H, s, NH). 13C NMR (125 MHz, CDCl3): δ=24.6 (C(CH3)2), 26.7 (C(CH3)2), 27.32, 27.33 (C(CH3)3), 28.4 (CH2S), 46.6 (C(CH3)3), 65.6, 66.36, 66.40, 66.75, 66.79 (CHCH2OP + POCH2), 74.96 (CHCH2OP), 75.85 (COCH), 110.7 (C(CH3)2), 165.25 ppm (HNCO). 31P NMR (202 MHz, CDCl3): δ=−2.00 ppm; LRMS (ES+): m/z (%) 560 (100) [M+H]+, 561 (25) [M+H]+, 1119 (35) [2M+H]+. HRMS (ES+) required for C21H39NO10PS2: 560.1748, found: 560.1747. LC-M: Rt 8.6 min; m/z 560; purity 99% by TIC trace.
|
2,2-Dimethyl-thiopropionic acid S-{2-[[2-(2,2-dimethyl-propionylsulfanyl)-ethoxy]-(5-hydroxycarbamoyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phosphoryloxy]-ethyl} ester
|
CC(C)(C)C(OCCOP(OCC1OC(C)(C)O[C@@H]1C(NO)=O)(OCCSC(C(C)(C)C)=O)=O)=S
|
1H NMR (500 MHz, CDCl3): δ=1.17, 1.17 (18H, 2 s, C(CH3)3), 1.30 (3H, s, C(CH3)2), 1.47 (3H, s, C(CH3)2), 3.06 (2H, t, J=6.8 Hz, CH2S), 3.09 (2H, t, J=6.7 Hz, CH2S), 4.00–4.05 (2H, m, CHCH2OP), 4.06–4.20 (4H, m, 2×POCH2CHS), 4.49–4.53 (1H, m, CHCH2OP), 4.68 (1H, d, J=7.5 Hz, COCH), 7.72 (1H, bs, OH), 8.90 ppm (1H, s, NH)
|
13C NMR (125 MHz, CDCl3): δ=24.6 (C(CH3)2), 26.7 (C(CH3)2), 27.32, 27.33 (C(CH3)3), 28.4 (CH2S), 46.6 (C(CH3)3), 65.6, 66.36, 66.40, 66.75, 66.79 (CHCH2OP + POCH2), 74.96 (CHCH2OP), 75.85 (COCH), 110.7 (C(CH3)2), 165.25 ppm (HNCO)
|
500 MHz, CDCl3
|
1.17, 1.17 (18H, 2 s, C(CH3)3), 1.30 (3H, s, C(CH3)2), 1.47 (3H, s, C(CH3)2), 3.06 (2H, t, J=6.8 Hz, CH2S), 3.09 (2H, t, J=6.7 Hz, CH2S), 4.00–4.05 (2H, m, CHCH2OP), 4.06–4.20 (4H, m, 2×POCH2CHS), 4.49–4.53 (1H, m, CHCH2OP), 4.68 (1H, d, J=7.5 Hz, COCH), 7.72 (1H, bs, OH), 8.90 ppm (1H, s, NH)
|
125 MHz, CDCl3
|
24.6, 26.7, 27.32, 27.33, 28.4, 46.6, 65.6, 66.36, 66.40, 66.75, 66.79, 74.96, 75.85, 110.7, 165.25
| 0.835064
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2-{[5-(4-Methoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid methyl ester (25a). To a cooled (−78°C) solution of 4a (31 mg, 0.1 mmol) and 5c (111 mg, 0.4 mmol) in dry THF (2 mL), NMI (0.048 mL, 0.6 mmol) was added dropwise with a syringe over 1 min. The reaction was stirred for 5 min at −78°C, then 6 h at room temperature and it was kept for the weekend in the freezer. TLC still revealed presence of the starting materials and the mixture was stirred for further 8 h at room temperature. The solvent was removed under reduced pressure. The crude yellowish residue was taken in DCM (10 mL) and washed with HCl 0.1m (2×10 mL). The organic phase was dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting colourless oil was purified by chromatography (SiO2, MeOH 0%→2% in DCM). Compound 25a was obtained as a yellow oil, 44 mg, 79%. 1H NMR (500 MHz, CDCl3): δ=1.28–1.41 (9H, m, CHCH3 + C(CH3)2), 3.69, 3.70 (3H, 2 s, CO2CH3), 3.81, 3.83 (3H, 2 s, PhOCH3), 4.05–4.20 (2H, m, CHCH3 + CHCHHOP), 4.41–4.50 (1H, m, CHCHHOP), 4.57–4.69 (2H, m, COCH + CHCH2OP), 4.88 (2H, s, ArCH2), 6.90 (2H, t, J=8.4 Hz, Ph-H), 7.12–7.16 (1H, m, Ph-H), 7.20–7.22 (2H, m, Ph-H), 7.27–7.38 (4H, m, Ar-H), 8.83, 9.13 ppm (1H, 2 s, NH). 31P NMR (202 MHz, CDCl3): δ=2.08, 2.58 ppm. 2-{[5-(2,4-Dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid methyl ester (25b). Same procedure as 25a. Starting from 4b (150 mg, 0.44 mmol), 5c (3.51 mL of solution 0.5m in DCM, 1.76 mmol) and NMI (0.210 mL, 2.64 mmol). Purified by chromatography eluting the silica with MeOH 0→2% in DCM. The title compound was obtained as colourless oil, slightly contaminated with starting material, 84 mg, 33%. 1H NMR (500 MHz, CDCl3): δ=1.20–1.33 (9H, m, CHCH3 + C(CH3)2), 3.59, 3.60 (3H, 2 s, CO2CH3), 3.72, 3.74 (6H, 2 s, OCH3), 3.94–4.08 (2H, m, CHHOP, CHCH3) 4.33–4.43 (1H, m, CHHOP), 4.49–4.59 (2H, m, COCHCHCH2), 4.82–4.89 (2H, m, ArCH2), 6.38–6.40 (2H, m, Ph-H), 7.02–7.24 (4H, m, Ar-H + Ph-H), 8.84, 9.06 ppm (1H, 2 s, NH). 13C NMR (125 MHz, CDCl3): δ=20.9, 21.0, 21.1 (C(CH3)3), 24.5, 24.6 (C(CH3)2), 26.5, 26.7 (C(CH3)2), 49.9, 50.1 (CHCH3), 52.3, 52.4 (CO2CH3), 55.4, 55.5 (PhOCH3), 64.9, 65.0, 65.2, 65.24 (CH2OP), 73.5 (ArCH2), 74.9, 75.3 (CHCHCH2) 76.0, 76.11, (COCHCH), 98.5 (Ar-CH), 104.1 (Ar-CH), 120.27, 120.32, 120.36, 120.4 (Ph-CH), 124.5, 124.7 (Ph-CH), 129.5, 129.6 (Ph-CH), 132.8 ppm (Ar-CH). In the 13C NMR all quaternary carbons are absent (7 in total). 31P NMR (202 MHz, CDCl3): δ=2.58, 2.78 ppm.
|
2-{[5-(4-Methoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-phenoxy-phosphorylamino}-propionic acid methyl ester
|
CC(NP(OC1=CC=CC=C1)(OCC2OC(C)(C)OC2C(NOCC3=CC=C(OC)C=C3)=O)=O)C(OC)=O
|
1H NMR (500 MHz, CDCl3): δ=1.28–1.41 (9H, m, CHCH3 + C(CH3)2), 3.69, 3.70 (3H, 2 s, CO2CH3), 3.81, 3.83 (3H, 2 s, PhOCH3), 4.05–4.20 (2H, m, CHCH3 + CHCHHOP), 4.41–4.50 (1H, m, CHCHHOP), 4.57–4.69 (2H, m, COCH + CHCH2OP), 4.88 (2H, s, ArCH2), 6.90 (2H, t, J=8.4 Hz, Ph-H), 7.12–7.16 (1H, m, Ph-H), 7.20–7.22 (2H, m, Ph-H), 7.27–7.38 (4H, m, Ar-H), 8.83, 9.13 ppm (1H, 2 s, NH)
|
13C NMR (125 MHz, CDCl3): δ=20.9, 21.0, 21.1 (C(CH3)3), 24.5, 24.6 (C(CH3)2), 26.5, 26.7 (C(CH3)2), 49.9, 50.1 (CHCH3), 52.3, 52.4 (CO2CH3), 55.4, 55.5 (PhOCH3), 64.9, 65.0, 65.2, 65.24 (CH2OP), 73.5 (ArCH2), 74.9, 75.3 (CHCHCH2) 76.0, 76.11, (COCHCH), 98.5 (Ar-CH), 104.1 (Ar-CH), 120.27, 120.32, 120.36, 120.4 (Ph-CH), 124.5, 124.7 (Ph-CH), 129.5, 129.6 (Ph-CH), 132.8 ppm (Ar-CH)
|
500 MHz, CDCl3
|
1.28–1.41 (9H, m, CHCH3 + C(CH3)2), 3.69, 3.70 (3H, 2 s, CO2CH3), 3.81, 3.83 (3H, 2 s, PhOCH3), 4.05–4.20 (2H, m, CHCH3 + CHCHHOP), 4.41–4.50 (1H, m, CHCHHOP), 4.57–4.69 (2H, m, COCH + CHCH2OP), 4.88 (2H, s, ArCH2), 6.90 (2H, t, J=8.4 Hz, Ph-H), 7.12–7.16 (1H, m, Ph-H), 7.20–7.22 (2H, m, Ph-H), 7.27–7.38 (4H, m, Ar-H), 8.83, 9.13 ppm (1H, 2 s, NH)
|
125 MHz, CDCl3
|
20.9, 21.0, 21.1, 24.5, 24.6, 26.5, 26.7, 49.9, 50.1, 52.3, 52.4, 55.4, 55.5, 64.9, 65.0, 65.2, 65.24, 73.5, 74.9, 75.3, 76.0, 76.11, 98.5, 104.1, 120.27, 120.32, 120.36, 120.4, 124.5, 124.7, 129.5, 129.6, 132.8
| 0.457481
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2-[(5-Hydroxycarbamoyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenoxy-phosphorylamino]-propionic acid methyl ester (3b). 25b (84 mg, 0.14 mmol) was dissolved in a solution of TFA 2% in DCM (2 mL). The reaction was stirred 15 min at room temperature; until the complete disappearance of the starting material was observed by TLC (2% MeOH in DCM) and the solution became deep purple. The mixture was diluted with DCM (5 mL), treated with diethyl ether (5 mL). The white precipitate was filtered and the solution was concentrated under reduced pressure and purified by chromatography. SiO2 eluted with MeOH 0%→7.5% in DCM. The phosphoramidate 3b was obtained as colourless oil, 19 mg, 22%. 1H NMR (500 MHz, CDCl3): δ=1.26–1.30 (6H, m, C(CH3)2), 1.42, 1.44 (3H, 2 s, CHCH3), 3.64, 3.65 (3H, 2 s, OCH3), 3.92–4.22 (4H, m, CHCH3 + CH2OP + OH), 4.49–4.54 (1H, m, CHCH2OP), 4.68 (1H, t, J=7.4 Hz, COCHCH), 7.07–7.10 (1H, m, Ph-H), 7.13–7.16 (2H, m, Ph-H), 7.23–7.26 (2H, m, Ph-H), 8.32 (1H, bs, NH), 8.96 ppm (1H, bs, NH). 13C NMR (125 MHz, CDCl3): δ=20.87, 20.93 (CHCH3), 24.57, 24.59 (C(CH3)2), 26.39, 26.68 (C(CH3)2), 50.0, 50.2 (CHCH3), 52.6 (OCH3), 64.9, 65.4 (CH2OP), 74.8, 75.4 (CHCH2OP), 75.79, 75.87, 75.96, 76.05 (COCHCH), 109.7 (C(CH3)2), 120.2, 120.3 (Ph-CH), 124.9, 125.0 (Ph-CH), 129.7 (Ph-CH), 149.5 (Ph-C), 165.1 ppm (HNCOCH), 173.8 (CO2CH3); 31P NMR (202 MHz, CDCl3): δ=2.49, 2.65 ppm; LRMS (ES+) m/z (%) 433 (100) [M+H]+, 434 (23) [M+H]+, 455 (95) [M+Na]+, 456 (19) [M+Na]+. HRMS (ES+) required for C17H26N2O9P 433.1370, found 433.1397. LC-M: Rt 7.6 min; m/z 433; purity 99% by UV and TIC traces.
|
2-[(5-Hydroxycarbamoyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-phenoxy-phosphorylamino]-propionic acid methyl ester
|
CC(NP(OC1=CC=CC=C1)(OCC2OC(C)(C)OC2C(NO)=O)=O)C(OC)=O
|
1H NMR (500 MHz, CDCl3): δ=1.26–1.30 (6H, m, C(CH3)2), 1.42, 1.44 (3H, 2 s, CHCH3), 3.64, 3.65 (3H, 2 s, OCH3), 3.92–4.22 (4H, m, CHCH3 + CH2OP + OH), 4.49–4.54 (1H, m, CHCH2OP), 4.68 (1H, t, J=7.4 Hz, COCHCH), 7.07–7.10 (1H, m, Ph-H), 7.13–7.16 (2H, m, Ph-H), 7.23–7.26 (2H, m, Ph-H), 8.32 (1H, bs, NH), 8.96 ppm (1H, bs, NH)
|
13C NMR (125 MHz, CDCl3): δ=20.87, 20.93 (CHCH3), 24.57, 24.59 (C(CH3)2), 26.39, 26.68 (C(CH3)2), 50.0, 50.2 (CHCH3), 52.6 (OCH3), 64.9, 65.4 (CH2OP), 74.8, 75.4 (CHCH2OP), 75.79, 75.87, 75.96, 76.05 (COCHCH), 109.7 (C(CH3)2), 120.2, 120.3 (Ph-CH), 124.9, 125.0 (Ph-CH), 129.7 (Ph-CH), 149.5 (Ph-C), 165.1 ppm (HNCOCH), 173.8 (CO2CH3); 31P NMR (202 MHz, CDCl3): δ=2.49, 2.65 ppm
|
500 MHz, CDCl3
|
1.26–1.30 (6H, m, C(CH3)2), 1.42, 1.44 (3H, 2 s, CHCH3), 3.64, 3.65 (3H, 2 s, OCH3), 3.92–4.22 (4H, m, CHCH3 + CH2OP + OH), 4.49–4.54 (1H, m, CHCH2OP), 4.68 (1H, t, J=7.4 Hz, COCHCH), 7.07–7.10 (1H, m, Ph-H), 7.13–7.16 (2H, m, Ph-H), 7.23–7.26 (2H, m, Ph-H), 8.32 (1H, bs, NH), 8.96 ppm (1H, bs, NH)
|
125 MHz, CDCl3
|
20.87, 20.93, 24.57, 24.59, 26.39, 26.68, 50.0, 50.2, 52.6, 64.9, 65.4, 74.8, 75.4, 75.79, 75.87, 75.96, 76.05, 109.7, 120.2, 120.3, 124.9, 125.0, 129.7, 149.5, 165.1, 173.8
| 0.424432
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2-[[5-(2,4-Dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-(4-nitro-phenoxy)-phosphorylamino]-propionic acid methyl ester (25c). NMI (0.210 mL, 2.64 mmol) was added dropwise into a solution of 4b (150 mg, 0.44 mmol), 5d (425 mg, 1.32 mmol) in dry DCM (10 mL) at −78°C under Argon. The reaction was at stirred room temperature for 48 h. The solution was washed with HCl 0.1n (3×10 mL). The organic phase was dried over Na2SO4, concentrated under reduced pressure, and purified by chromatography. SiO2 eluted with MeOH 0%→0.1% in Chloroform. The title compound was obtained as yellowish oil, slightly contaminated of starting alcohol 4b, 60 mg (29%) and was used for the next step without further purification. 1H NMR (500 MHz, CDCl3): δ=1.30, 1.32 (6H, 2 s, C(CH3)2), 1.42, 1.46 (3H, 2 s, CHCH3), 3.68 (3H, s, OCH3), 4.04–4.09 (1H, m, CHCH3), 4.15–4.23 (2H, m, CH2OP), 4.53 (1H, bs, CHCH2OP), 4.70 (1H, d, J=7.5 Hz, COCHCH), 6.42 (2H, m, Ar-CH2), 7.31 (2H, m, Ar-H), 8.16 (2H, m, Ar-H), 8.93 ppm (1H, bs, NH). 31P NMR (202 MHz, CDCl3): δ=2.30, 1.77 ppm; LRMS (ES+): m/z (%) 626.5 (100) [M+H]+, 645.6 (85) [M+NH4]+, 650.5 (75) [M+Na]+. 2-[(5-Hydroxycarbamoyl-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-(4-nitro-phenoxy)-phosphorylamino]-propionic acid methyl ester (3c). The protected hydroxamate 25c (14 mg, 0.022 mmol) was stirred in a solution of 1% TFA in DCM (2 mL). After 15 min the solution turned deep purple and the TLC (5% MeOH in DCM) showed the complete disappearance of the starting material. The solution was concentrated under reduced pressure. The residue taken in MeOH (2 mL) the white precipitate was filtered and the solution was purified by chromatography eluting the silica with MeOH 0%→5% in DCM. The p-nitro phosphoramidate 3c was obtained as yellowish gum, 5 mg, 11%. 1H NMR (500 MHz, CDCl3): δ=1.30, 1.32 (6H, 2 s, C(CH3)2), 1.42, 1.46 (3H, 2 s, CHCH3), 3.68 (3H, s, OCH3), 4.04–4.09 (1H, m, CHCH3), 4.15–4.23 (2H, m, CH2OP), 4.53 (1H, bs, CHCH2OP), 4.70 (1H, d, J=7.5 Hz, COCHCH), 7.31 (2H, d, J=8.7 Hz, Ar-H), 8.16 (2H, d, J=9.0 Hz, Ar-H), 8.93 ppm (1H, bs, NH); 13C NMR (125 MHz, CDCl3): δ=20.0 (CHCH3), 24.25 (C(CH3)2), 26.67 (C(CH3)2), 50.0, 50.2 (CHCH3), 53.5 (OCH3), 65.1, 65.2 (CH2OP), 75.5, 75.6 (CHCH2OP), 77.6 (COCHCH), 110.5 (C(CH3)2), 120.8, 120.9 (Ph-CH), 125.6, (Ph-CH), 130.7 (Ph-C-NO2), 142.6 (Ph-C), 166.0 (HNCOCH), 173.8 ppm (CO2CH3); 31P NMR (202 MHz, CDCl3): δ=2.10, 1.90 ppm; LRMS (ES+): m/z 499.5 ([M+Na]+ 100%), 477.5 ([M+H]+, 40%); LRMS (ES+) m/z (%) 478 (10) [M+H]+, 479 (24) [M+H]+, 500 (18) [M+Na]+, 537 (6) [M+K]+. HRMS (ES+) required for C17H25N3O11P 478.1221, found 478.1218. LC-M: Rt 7.6 min; m/z 478; purity 80% by UV and TIC traces.
|
2-[[5-(2,4-Dimethoxy-benzyloxycarbamoyl)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy]-(4-nitro-phenoxy)-phosphorylamino]-propionic acid methyl ester
|
CC(NP(OC1=CC=C([N+]([O-])=O)C=C1)(OCC2OC(C)(C)OC2C(NOCC3=CC=C(OC)C=C3OC)=O)=O)C(OC)=O
|
1H NMR (500 MHz, CDCl3): δ=1.30, 1.32 (6H, 2 s, C(CH3)2), 1.42, 1.46 (3H, 2 s, CHCH3), 3.68 (3H, s, OCH3), 4.04–4.09 (1H, m, CHCH3), 4.15–4.23 (2H, m, CH2OP), 4.53 (1H, bs, CHCH2OP), 4.70 (1H, d, J=7.5 Hz, COCHCH), 6.42 (2H, m, Ar-CH2), 7.31 (2H, m, Ar-H), 8.16 (2H, m, Ar-H), 8.93 ppm (1H, bs, NH)
|
13C NMR (125 MHz, CDCl3): δ=20.0 (CHCH3), 24.25 (C(CH3)2), 26.67 (C(CH3)2), 50.0, 50.2 (CHCH3), 53.5 (OCH3), 65.1, 65.2 (CH2OP), 75.5, 75.6 (CHCH2OP), 77.6 (COCHCH), 110.5 (C(CH3)2), 120.8, 120.9 (Ph-CH), 125.6, (Ph-CH), 130.7 (Ph-C-NO2), 142.6 (Ph-C), 166.0 (HNCOCH), 173.8 ppm (CO2CH3)
|
500 MHz, CDCl3
|
1.30, 1.32 (6H, 2 s, C(CH3)2), 1.42, 1.46 (3H, 2 s, CHCH3), 3.68 (3H, s, OCH3), 4.04–4.09 (1H, m, CHCH3), 4.15–4.23 (2H, m, CH2OP), 4.53 (1H, bs, CHCH2OP), 4.70 (1H, d, J=7.5 Hz, COCHCH), 6.42 (2H, m, Ar-CH2), 7.31 (2H, m, Ar-H), 8.16 (2H, m, Ar-H), 8.93 ppm (1H, bs, NH)
|
125 MHz, CDCl3
|
20.0, 24.25, 26.67, 50.0, 50.2, 53.5, 65.1, 65.2, 75.5, 75.6, 77.6, 110.5, 120.8, 120.9, 125.6, 130.7, 142.6, 166.0, 173.8
| 0.246721
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2-Chloro-4H-benzo[1,3,2]dioxaphosphinine (6b). A solution of triethylamine (11.8 mL, 84.6 mmol) in dry ether (70 mL) was added dropwise over 1.5 h into a solution of PCl3 (6.2 mL, 44.3 mmol) and 2-hydroxy benzyl alcohol (5 g, 40.3 mmol) in dry ether (100 mL) at −78°C. The white suspension was vigorously stirred at room temperature for 1.5 h. The hydrochloride salt was filtered off and the solution was first concentrated at room temperature with the rotary evaporator and then distilled under reduced pressure (5 mbar, 80–93°C), avoiding any contact with air. The cyclosal chloro phosphine was obtained as colourless liquid (2.56 g, 34%). 1H NMR (500 MHz, CDCl3): δ=5.07 (1H, dd, J1=14.2, J2=9.6 Hz, Ar-CHHO), 5.49 (1H, dd, J1=14.4, J2=1.9 Hz, Ar-CHHO), 7.01–7.03 (2H, m, Ar-H), 7.15 (1H, t, J=7.5 Hz, Ar-H), 7.31 ppm (1H, t, J=7.5 Hz, Ar-H). 13C NMR (125 MHz, CDCl3): δ=61.13, 61.14 (ArCH2O), 119.47, 119.49 (Ar-CH), 121.44, 121.54 (Ar-C), 124.04 (Ar-CH), 125.84 (Ar-CH), 129.30 (Ar-CH), 146.13, 146.17 (Ar-C). 31P NMR (202 MHz, CDCl3): δ=139.95 ppm.
|
2-Chloro-4H-benzo[1,3,2]dioxaphosphinine
|
ClP1OC2=CC=CC=C2CO1
|
1H NMR (500 MHz, CDCl3): δ=5.07 (1H, dd, J1=14.2, J2=9.6 Hz, Ar-CHHO), 5.49 (1H, dd, J1=14.4, J2=1.9 Hz, Ar-CHHO), 7.01–7.03 (2H, m, Ar-H), 7.15 (1H, t, J=7.5 Hz, Ar-H), 7.31 ppm (1H, t, J=7.5 Hz, Ar-H)
|
13C NMR (125 MHz, CDCl3): δ=61.13, 61.14 (ArCH2O), 119.47, 119.49 (Ar-CH), 121.44, 121.54 (Ar-C), 124.04 (Ar-CH), 125.84 (Ar-CH), 129.30 (Ar-CH), 146.13, 146.17 (Ar-C)
|
500 MHz, CDCl3
|
5.07 (1H, dd, J1=14.2, J2=9.6 Hz, Ar-CHHO), 5.49 (1H, dd, J1=14.4, J2=1.9 Hz, Ar-CHHO), 7.01–7.03 (2H, m, Ar-H), 7.15 (1H, t, J=7.5 Hz, Ar-H), 7.31 ppm (1H, t, J=7.5 Hz, Ar-H)
|
125 MHz, CDCl3
|
61.13, 61.14, 119.47, 119.49, 121.44, 121.54, 124.04, 125.84, 129.30, 146.13, 146.17
| 0.727531
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
2,2-Dimethyl-5-(2-oxo-2,3-dihydro-2,5-benzo[1,4,2]dioxaphosphinin-2-yloxymethyl)-[1,3]dioxolane-4-carboxylic acid (2,4-dimethoxy-benzyloxy)-amide (28). 6b (166 mg, 0.88 mmol) was added over 5 min to a solution of 4b (150 mg, 0.44 mmol) and DIPEA (0.152 mL, 0.88 mmol) in dry CH3CN (10 mL) cooled with an ice bath. The reaction was kept 1 h at 0°C, until the TLC (10% MeOH in DCM) showed complete disappearance of the starting alcohol; then a solution of tert-butylhydroperoxide 70% in H2O (0.118 mL) was added. The mixture was stirred for further 2 h at room temperature. Na2SO3 10% in water (0.055 mL) was added to destroy the excess of peroxide. The reaction was diluted with DCM (10 mL) and washed with water/brine (10 mL). The organic phase was dried over Na2SO4, concentrated to dryness, and purified by chromatography. SiO2 eluted with DCM 10%→5% in EtOAc. The title compound was obtained as white foam, 84 mg, 37%. 1H NMR (500 MHz, CDCl3): δ=1.27 (3H, s, C(CH3)2), 1.38, 1.41 (3H, 2 s, C(CH3)2), 3.75 (6H, 2 s, OCH3), 4.04–4.16 (1H, m, CHCHHOP), 4.46–4.57 (3H, m, COCHCHCHHOP), 4.75 (1H, AB syst., J1=11.0, J2=28.4 Hz, ArCHHO), 4.80 (1H, AB syst., J1=11.0, J2=32.9 Hz, ArCHHO), 5.16–5.27 (1H, m, POCHHAr), 5.33–5.39 (1H, m, POCHHAr), 6.38–6.42 (2H, m, Ar-H), 6.92–7.04 (3H, m, Ar-H), 7.13–7.22 (2H, m, Ar-H), 8.71, 8.78 ppm (1H, 2 s, NH). 13C NMR (125 MHz, CDCl3): δ=24.55, 24.58 (C(CH3)2), 26.66, 26.73 (C(CH3)2), 55.44, 55.55, 55.58 (OCH3), 66.60, 66.66, 66.70 (CHCH2OP), 68.54, 68.60, 68.72 (POCH2Ar), 73.53, 73.57 (ArCH2O), 74.90, 75.02 (CHCH2OP), 75.81, 75.87 (COCH), 98.55, 98.57 (Ar-CH), 104.16, 104.19 (Ar-CH), 110.75 (C(CH3)2), 115.63 (Ar-CH), 118.61, 118.68, 118.77, 118.84 (Ar-CH), 120.66 (Ar-C), 124.13, 124.18 (Ar-CH), 125.23, 125.33 (Ar-CH), 129.60, 129.70 (Ar-CH), 132.80, 132.88 (Ar-C), 150.20 (Ar-C), 159.39, 159.43 (Ar-C), 161.83, 161.86 (Ar-C) 165.07, 165.22 ppm (HNCO). 31P NMR (202 MHz, CDCl3): δ=−9.63, −9.79 ppm. LRMS (ES+): m/z (%) 532 (100) [M+Na]+, 533 (22) [M+Na]+. HRMS (ES+) required for C23H28NNaO10P 532.1343, found 532.1316.
|
2,2-Dimethyl-5-(2-oxo-2,3-dihydro-2,5-benzo[1,4,2]dioxaphosphinin-2-yloxymethyl)-[1,3]dioxolane-4-carboxylic acid (2,4-dimethoxy-benzyloxy)-amide
| null |
1H NMR (500 MHz, CDCl3): δ=1.27 (3H, s, C(CH3)2), 1.38, 1.41 (3H, 2 s, C(CH3)2), 3.75 (6H, 2 s, OCH3), 4.04–4.16 (1H, m, CHCHHOP), 4.46–4.57 (3H, m, COCHCHCHHOP), 4.75 (1H, AB syst., J1=11.0, J2=28.4 Hz, ArCHHO), 4.80 (1H, AB syst., J1=11.0, J2=32.9 Hz, ArCHHO), 5.16–5.27 (1H, m, POCHHAr), 5.33–5.39 (1H, m, POCHHAr), 6.38–6.42 (2H, m, Ar-H), 6.92–7.04 (3H, m, Ar-H), 7.13–7.22 (2H, m, Ar-H), 8.71, 8.78 ppm (1H, 2 s, NH)
|
13C NMR (125 MHz, CDCl3): δ=24.55, 24.58 (C(CH3)2), 26.66, 26.73 (C(CH3)2), 55.44, 55.55, 55.58 (OCH3), 66.60, 66.66, 66.70 (CHCH2OP), 68.54, 68.60, 68.72 (POCH2Ar), 73.53, 73.57 (ArCH2O), 74.90, 75.02 (CHCH2OP), 75.81, 75.87 (COCH), 98.55, 98.57 (Ar-CH), 104.16, 104.19 (Ar-CH), 110.75 (C(CH3)2), 115.63 (Ar-CH), 118.61, 118.68, 118.77, 118.84 (Ar-CH), 120.66 (Ar-C), 124.13, 124.18 (Ar-CH), 125.23, 125.33 (Ar-CH), 129.60, 129.70 (Ar-CH), 132.80, 132.88 (Ar-C), 150.20 (Ar-C), 159.39, 159.43 (Ar-C), 161.83, 161.86 (Ar-C) 165.07, 165.22 ppm (HNCO)
|
500 MHz, CDCl3
|
1.27 (3H, s, C(CH3)2), 1.38, 1.41 (3H, 2 s, C(CH3)2), 3.75 (6H, 2 s, OCH3), 4.04–4.16 (1H, m, CHCHHOP), 4.46–4.57 (3H, m, COCHCHCHHOP), 4.75 (1H, AB syst., J1=11.0, J2=28.4 Hz, ArCHHO), 4.80 (1H, AB syst., J1=11.0, J2=32.9 Hz, ArCHHO), 5.16–5.27 (1H, m, POCHHAr), 5.33–5.39 (1H, m, POCHHAr), 6.38–6.42 (2H, m, Ar-H), 6.92–7.04 (3H, m, Ar-H), 7.13–7.22 (2H, m, Ar-H), 8.71, 8.78 ppm (1H, 2 s, NH)
|
125 MHz, CDCl3
|
24.55, 24.58, 26.66, 26.73, 55.44, 55.55, 55.58, 66.60, 66.66, 66.70, 68.54, 68.60, 68.72, 73.53, 73.57, 74.90, 75.02, 75.81, 75.87, 98.55, 98.57, 104.16, 104.19, 110.75, 115.63, 118.61, 118.68, 118.77, 118.84, 120.66, 124.13, 124.18, 125.23, 125.33, 129.60, 129.70, 132.80, 132.88, 150.20, 159.39, 159.43, 161.83, 161.86, 165.07, 165.22
| 0.667728
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
Cyclo(saligenyl)-(5-(hydroxycarbamoyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl phosphate ester (3f). Compound 28 (79 mg, 0.155 mmol) was stirred in a solution of TFA 2% in DCM (2 mL). The reaction was monitored by TLC (5% MeOH/DCM). The solution was concentrated under reduced pressure, suspended in MeOH (2 mL), and filtrate. The collected filtrate was concentrated and purified by chromatography eluting the silica with MeOH 0→5% in DCM. The cycloSal prodrug 3f was obtained as white foam, 39 mg, 69%. Rf 0.25 in (5% MeOH/DCM). 1H NMR (500 MHz, CDCl3): δ=1.38 (3H, s, C(CH3)2), 1.52, 1.55 (3H, 2 s, C(CH3)2), 4.41–4.46 (2H, m, CHCH2OP), 4.60–4.64 (1H, m, CHCH2OP), 4.76–4.78 (1H, m, COCH), 5.31–5.46 (2H, m, OCH2Ar), 7.09–7.11 (2H m, Ar-H), 7.17 (1H, t, J=7.5 Hz, Ar-H), 7.35 (1H, t, J=7.6 Hz, Ar-H), 8.93–9.02 ppm (1H, bs, NH). 13C NMR (125 MHz, CDCl3): δ=24.45, 24.58 (C(CH3)2), 26.47, 26.63 (C(CH3)2), 66.67, 66.72, 66.77 (CHCH2OP), 68.83, 68.88, 68.94 (POCH2Ar), 74.45, 74.67 (CHCH2OP), 75.66, 75.72 (COCHCH), 110.87, 110.95 (C(CH3)2), 118.66, 118.73, 118.75, 118.83 (Ar-CH), 120.57, 120.65, 120.72 (Ar-C), 124.40 (Ar-CH), 125.33, 125.41 (Ar-CH), 129.75, 129.78 (Ar-CH), 149.92, 149.94, 149.97, 150.0 (Ar-C), 165.7, 166.0 ppm (HNCO). 31P NMR (202 MHz, CDCl3): δ=−9.74, −9.83 ppm. LRMS (ES+): m/z (%) 360 (100) [M+H]+, 379 (85) [M+Na]+. HRMS (ES+): required 382.0662 for C14H18NNaO8P, found 382.0659. LC-M: Rt 7.2 min; m/z 360; purity 99% by UV and TIC traces.
|
Cyclo(saligenyl)-(5-(hydroxycarbamoyl)-2,2-dimethyl-1,3-dioxolan-4-yl)methyl phosphate ester
| null |
1H NMR (500 MHz, CDCl3): δ=1.38 (3H, s, C(CH3)2), 1.52, 1.55 (3H, 2 s, C(CH3)2), 4.41–4.46 (2H, m, CHCH2OP), 4.60–4.64 (1H, m, CHCH2OP), 4.76–4.78 (1H, m, COCH), 5.31–5.46 (2H, m, OCH2Ar), 7.09–7.11 (2H m, Ar-H), 7.17 (1H, t, J=7.5 Hz, Ar-H), 7.35 (1H, t, J=7.6 Hz, Ar-H), 8.93–9.02 ppm (1H, bs, NH)
|
13C NMR (125 MHz, CDCl3): δ=24.45, 24.58 (C(CH3)2), 26.47, 26.63 (C(CH3)2), 66.67, 66.72, 66.77 (CHCH2OP), 68.83, 68.88, 68.94 (POCH2Ar), 74.45, 74.67 (CHCH2OP), 75.66, 75.72 (COCHCH), 110.87, 110.95 (C(CH3)2), 118.66, 118.73, 118.75, 118.83 (Ar-CH), 120.57, 120.65, 120.72 (Ar-C), 124.40 (Ar-CH), 125.33, 125.41 (Ar-CH), 129.75, 129.78 (Ar-CH), 149.92, 149.94, 149.97, 150.0 (Ar-C), 165.7, 166.0 ppm (HNCO)
|
500 MHz, CDCl3
|
1.38 (3H, s, C(CH3)2), 1.52, 1.55 (3H, 2 s, C(CH3)2), 4.41–4.46 (2H, m, CHCH2OP), 4.60–4.64 (1H, m, CHCH2OP), 4.76–4.78 (1H, m, COCH), 5.31–5.46 (2H, m, OCH2Ar), 7.09–7.11 (2H m, Ar-H), 7.17 (1H, t, J=7.5 Hz, Ar-H), 7.35 (1H, t, J=7.6 Hz, Ar-H), 8.93–9.02 ppm (1H, bs, NH)
|
125 MHz, CDCl3
|
24.45, 24.58, 26.47, 26.63, 66.67, 66.72, 66.77, 68.83, 68.88, 68.94, 74.45, 74.67, 75.66, 75.72, 110.87, 110.95, 118.66, 118.73, 118.75, 118.83, 120.57, 120.65, 120.72, 124.40, 125.33, 125.41, 129.75, 129.78, 149.92, 149.94, 149.97, 150.0, 165.7, 166.0
| 0.75146
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
PMC2248282
|
Tris((pivaloyloxy)methyl) phosphate (18). Chloromethyl pivalate (6.05 mL, 41.7 mmol) and NaI (4.84 g, 32.1 mmol) were added into a solution of trimethyl phosphate (1.24 mL, 10.7 mmol) in CH3CN (9 mL). The solution was refluxed (80°C) for 3 days, cooled to room temperature and diluted with diethyl ether (100 mL). The organic solution was washed with water (3×20 mL), dried over Na2SO4, concentrated and purified by chromatography eluting the column with 30% EtOAc in hexane. Compound 18 was obtained as colourless oil, 3.31 g (70%). Rf 0.47 (30% EtOAc/hexane). 1H NMR (500 MHz, CDCl3): δ=1.25 (27H, d, J=1.53 Hz, 3×C(CH3)3), 5.68 ppm (6H, dd, J=1.4, 13.8 Hz, 3×OCH2O). 13C NMR (125 MHz, CDCl3): δ=26.8 (C(CH3)3), 38.8 (C(CH3)3), 82.77 (d, J=5.2 Hz, OCH2O), 176.6 ppm (COC(CH3)3). 31P NMR (202 MHz, CDCl3): δ=−5.1 ppm.
|
Tris((pivaloyloxy)methyl) phosphate
|
O=P(OCOC(C(C)(C)C)=O)(OCOC(C(C)(C)C)=O)OCOC(C(C)(C)C)=O
|
1H NMR (500 MHz, CDCl3): δ=1.25 (27H, d, J=1.53 Hz, 3×C(CH3)3), 5.68 ppm (6H, dd, J=1.4, 13.8 Hz, 3×OCH2O)
|
13C NMR (125 MHz, CDCl3): δ=26.8 (C(CH3)3), 38.8 (C(CH3)3), 82.77 (d, J=5.2 Hz, OCH2O), 176.6 ppm (COC(CH3)3)
|
500 MHz, CDCl3
|
1.25 (27H, d, J=1.53 Hz, 3×C(CH3)3), 5.68 ppm (6H, dd, J=1.4, 13.8 Hz, 3×OCH2O)
|
125 MHz, CDCl3
|
26.8, 38.8, 82.77, 176.6
| 0.903314
| 17,615,587
|
ChemMedChem. 2007 Aug 13; 2(8):1169-1180
|
ChemMedChem
| 2,007
|
CC BY
|
2021-01-04 20:13:23
|
no
|
End of preview.
1. NMRBank data (225809)
We batch processed 380,220 NMR segments using NMRExtractor. After removing entries with empty 13C NMR chemical shifts, we obtained about 260,000 entries. Further filtering out entries with empty IUPAC names and NMR chemical shifts resulted in 225,809 entries.
NMRBank_data_225809.zip
2. NMRBank data with SMILES (156621)
To normalize these data, we converted IUPAC names to SMILES using ChemDraw and OPSIN, successfully converting 156,621 entries. We then normalized SMILES using RDKit.
NMRBank_data_with_SMILES_156621_in_225809.zip
We have normalized the dataset based on standardized SMILES strings. The total number of unique SMILES strings is 149,135.
NMRBank_data_with_unique_SMILES_149135_in_156621.zip
For the highest confidence interval (0.6–1), the number of unique SMILES records is 123,174.
NMRBank_data_with_unique_SMILES_and_confidence_greater_than_0.6_123174_in_149135.zip
For the highest confidence interval (0.8–1), the number of unique SMILES records is 91,707.
NMRBank_data_with_unique_SMILES_and_confidence_greater_than_0.8_91707_in_149135.zip
3. NMRBank dataset in json format
We also provide the NMRBank dataset in JSON format for convenient access and easy viewing.
NMRBank_json_format\NMRBank_data_225809_json_format.zipNMRBank_json_format\NMRBank_json_format\NMRBank_data_with_SMILES_156621_in_225809_json_format.zipNMRBank_json_format\NMRBank_data_with_unique_SMILES_149135_in_156621_json_format.zipNMRBank_json_format\NMRBank_data_with_unique_SMILES_and_confidence_greater_than_0.6_123174_in_149135_json_format.zipNMRBank_json_format\NMRBank_data_with_unique_SMILES_and_confidence_greater_than_0.8_91707_in_149135_json_format.zip
4. NMRBank dataset reading and viewing
Read csv file
import pandas as pd
# Reading csv Files
df = pd.read_csv(r"NMRBank_data_225809.csv", encoding="utf-8")
df
Read json file
import pandas as pd
# Reading json Files
df = pd.read_json(r"NMRBank_data_225809.json", orient="records", lines=True)
df
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