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【结 构 式】 
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【分子编号】47771 【品名】(4S,4aS,7R,7aS)-7-methoxy-2,2-dimethyl-6-oxotetrahydro-4H-furo[3,2-d][1,3]dioxine-4-carbaldehyde 【CA登记号】 |
【 分 子 式 】C10H14O6 【 分 子 量 】230.21756 【元素组成】C 52.17% H 6.13% O 41.7% |
合成路线1
该中间体在本合成路线中的序号：(V)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：(V)alpha-D-Glucoheptonic acid gamma-lactone (I) was protected as the bis(acetonide) (II) upon treatment with a catalytic amount of I2 in acetone. The free hydroxyl group of (II) was then alkylated with iodomethane in the presence of silver oxide, yielding the methyl ether (III). Selective hydrolysis of the 1,2-acetonide of (III) was accomplished by treatment of the bis(acetonide) (III) with aqueous acetic acid. Oxidative cleavage of the resultant vicinal diol (IV) using NaIO4 gave aldehyde (V). Then, olefination of aldehyde (V) with the low-valent organochromium species generated in situ from 1,1-diiodoneopentane (VI) and CrCl2 produced the target E-olefin (VII) as the major isomer.
| 【1】 Kinder, F.R. Jr.; Versace, R.W.; Bair, K.W.; et al.; Synthesis and antitumor activity of ester-modified analogues of bengamide B. J Med Chem 2001, 44, 22, 3692. |
| 【2】 Bair, K.W.; Wattanasin, S.; Versace, R.W.; Kinder, F.R. Jr.; Jagoe, C.T. (Novartis AG); Certain substd. caprolactams, pharmaceutical compsns. containing them and a process for their preparation. US 6239127 . |
| 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) | 54664 | 1,1-Diiodo-2,2-dimethypropane | C5H10I2 | 详情 | 详情 | |
| (VII) | 54665 | (4R,4aR,7R,7aS)-4-[(E)-3,3-dimethyl-1-butenyl]-7-methoxy-2,2-dimethyltetrahydro-6H-furo[3,2-d][1,3]dioxin-6-one | C15H24O5 | 详情 | 详情 |