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【结 构 式】 
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【分子编号】47773 【品名】(4R,4aR,7R,7aS)-7-methoxy-2,2-dimethyl-4-[(E)-3-methyl-1-butenyl]tetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one 【CA登记号】 |
【 分 子 式 】C14H22O5 【 分 子 量 】270.32568 【元素组成】C 62.2% H 8.2% O 29.59% |
合成路线1
该中间体在本合成路线中的序号：(VII)The intermediate lactone (VII) was prepared as follows. Alpha-D-glucoheptonic gamma-lactone (I) was converted to the bis(acetonide) (II) by treatment with I2 in acetone. Methylation of the free hydroxyl group of (II) using Ag2O and methyl iodide provided the methyl ether (III). Selective removal of 1,2-acetonide of (III) in the presence of the 1,3-acetonide was accomplished by treatment of (III) with acetic acid. The resulting vicinal diol (IV) was then subjected to oxidative cleavage with NaIO4 to produce aldehyde (V). This was then olefinated with the low-valent organochromium species generated in situ from 1,1-diiodoisobutane (VI) and CrCl2 to produce the E-olefin (VII) as the major isomer, which was isolated using preparative HPLC.
| 【1】 Kinder, F.R. Jr.; et al.; Total synthesis of bengamides B and E. J Org Chem 2001, 66, 6, 2118. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (I) | 47767 | (3R,4S,5S)-3,4-dihydroxy-5-[(1R,2R)-1,2,3-trihydroxypropyl]dihydro-2(3H)-furanone | C7H12O7 | 详情 | 详情 | |
| (II) | 47768 | (4R,4aS,7R,7aS)-4-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-7-hydroxy-2,2-dimethyltetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one | C13H20O7 | 详情 | 详情 | |
| (III) | 47769 | (4R,4aS,7R,7aS)-4-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-7-methoxy-2,2-dimethyltetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one | C14H22O7 | 详情 | 详情 | |
| (IV) | 47770 | (4R,4aR,7R,7aS)-4-[(1R)-1,2-dihydroxyethyl]-7-methoxy-2,2-dimethyltetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one | C11H18O7 | 详情 | 详情 | |
| (V) | 47771 | (4S,4aS,7R,7aS)-7-methoxy-2,2-dimethyl-6-oxotetrahydro-4H-furo[3,2-d][1,3]dioxine-4-carbaldehyde | C10H14O6 | 详情 | 详情 | |
| (VI) | 47772 | 1,1-diiodo-2-methylpropane | C4H8I2 | 详情 | 详情 | |
| (VII) | 47773 | (4R,4aR,7R,7aS)-7-methoxy-2,2-dimethyl-4-[(E)-3-methyl-1-butenyl]tetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one | C14H22O5 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)Cyclization of 5(R)-hydroxy-L-lysine (VIII) by means of EDC and HOBt, followed by treatment of the resulting amino lactam (IX) with Boc2O, furnished the N-Boc aminolactam (X). The configuration of the (R)-secondary alcohol was inverted by Mitsunobu coupling with p-nitrobenzoic acid (XI) to produce the (S)-p-nitrobenzoate ester (XII). Methylation of the lactam N of (XII) yielded (XIII), and hydrolysis of the p-nitrobenzoate ester of (XIII) with LiOH afforded the (S)-hydroxy lactam (XIV). Esterification of (XIV) with myristic acid (XV) in the presence of EDC and DMAP produced the myristate ester (XVI). Treatment of (XVI) with trifluoroacetic acid removed the Boc protecting group to yield amine (XVII). This was then condensed with the intermediate lactone (VIII) in refluxing isopropanol to produce amide (XVIII). Finally, acetonide hydrolysis in (XVIII) employing trifluoroacetic acid generated the title compound.
| 【1】 Kinder, F.R. Jr.; et al.; Total synthesis of bengamides B and E. J Org Chem 2001, 66, 6, 2118. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 47773 | (4R,4aR,7R,7aS)-7-methoxy-2,2-dimethyl-4-[(E)-3-methyl-1-butenyl]tetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one | C14H22O5 | 详情 | 详情 | |
| (VIII) | 47774 | (2S,5R)-2,6-diamino-5-hydroxyhexanoic acid | C6H14N2O3 | 详情 | 详情 | |
| (IX) | 47775 | (3S,6R)-3-amino-6-hydroxy-2-azepanone | C6H12N2O2 | 详情 | 详情 | |
| (X) | 47776 | tert-butyl (3S,6R)-6-hydroxy-2-oxoazepanylcarbamate | C11H20N2O4 | 详情 | 详情 | |
| (XI) | 18119 | 4-nitrobenzoic acid; p-nitrobenzoic acid | 62-23-7 | C7H5NO4 | 详情 | 详情 |
| (XII) | 47777 | (3S,6S)-6-[(tert-butoxycarbonyl)amino]-7-oxoazepanyl 4-nitrobenzoate | C18H23N3O7 | 详情 | 详情 | |
| (XIII) | 47778 | (3S,6S)-6-[(tert-butoxycarbonyl)amino]-1-methyl-7-oxoazepanyl 4-nitrobenzoate | C19H25N3O7 | 详情 | 详情 | |
| (XIV) | 47779 | tert-butyl (3S,6S)-6-hydroxy-1-methyl-2-oxoazepanylcarbamate | C12H22N2O4 | 详情 | 详情 | |
| (XV) | 47780 | myristic acid | C14H28O2 | 详情 | 详情 | |
| (XVI) | 47781 | (3S,6S)-6-[(tert-butoxycarbonyl)amino]-1-methyl-7-oxoazepanyl myristate | C26H48N2O5 | 详情 | 详情 | |
| (XVII) | 47783 | (3S,6S)-6-amino-1-methyl-7-oxoazepanyl myristate | C21H40N2O3 | 详情 | 详情 | |
| (XVIII) | 47782 | (3S,6S)-6-[((2R)-2-[(4R,5R,6R)-5-hydroxy-2,2-dimethyl-6-[(E)-3-methyl-1-butenyl]-1,3-dioxan-4-yl]-2-methoxyethanoyl)amino]-1-methyl-7-oxoazepanyl myristate | C35H62N2O8 | 详情 | 详情 |