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【结 构 式】 
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【分子编号】57997 【品名】methyl (6S)-6-hydroxy-8-oxooctanoate 【CA登记号】 |
【 分 子 式 】C9H16O4 【 分 子 量 】188.22364 【元素组成】C 57.43% H 8.57% O 34% |
合成路线1
该中间体在本合成路线中的序号：(LXXIV)The reaction of the chiral dibenzoyloxy-dihydropyran (LXV) with H2SO4 and HgSO4 gives the unsaturated aldehyde (LXVI), which is condensed with the phosphorane (LXVII) to yield the hepatdienoic ester (LXVIII). The hydrogenation of (LXVIII) with H2 over Pd/C affords the heptanoic ester (LXIX), which is treated with Ts-Cl and pyridine to provide the tosyloxy derivative (LXX). The cyclization of (LXX) by means of K2CO3 gives the chiral epoxide (LXXI), which is condensed with vinylmagnesium bromide (LXXII) to yield 6(S)-hydroxy-8-nonenoic acid methyl ester (LXXIII). The oxidation of the terminal double bond of (LXXIII) with ozone affords the carbaldehyde (LXXIV), which is reduced with NaBH4 to provide 6(S),8-dihydroxyoctanoic acid methyl ester (XLVIII). The reaction of (XLVIII) with Ms-Cl and pyridine gives the dimesylate (XLIX), which is treated with Na2S2 to yield the lipoic acid methyl ester (L), which is hydrolyzed to the target acid with KOH in H2O.
| 【1】 Adger, B.; et al.; The synthesis of (R)-(+)-lipoic acid using a monooxygenase-catalysed biotransformation as the key step. Bioorg Med Chem 1997, 5, 2, 253. |
| 【2】 Adger, B.; et al.; Application of enzymatic Baeyer-Villiger oxidations of 2-substituted cycloalkanones to the total synthesis of (R)-(+)-lipoic acid. J Chem Soc Chem Commun 1995, 15, 1563. |
| 【3】 McCague, R.; Roberts, S.M.; Adger, B.M. (Celltech Group plc); Process for the production of lipoic acid. WO 9638437 . |
| 【4】 Villani, F.; Nardi, A.; Salvi, A.; Falabella, G.; Synthesis of R(+)alpha-lipoic acid. WO 0230919 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XLVIII) | 57977 | methyl (6S)-6,8-dihydroxyoctanoate | C9H18O4 | 详情 | 详情 | |
| (XLIX) | 57975 | methyl (6S)-6,8-bis[(methylsulfonyl)oxy]octanoate | C11H22O8S2 | 详情 | 详情 | |
| (L) | 57976 | methyl 5-[(3R)-1,2-dithiolan-3-yl]pentanoate | C9H16O2S2 | 详情 | 详情 | |
| (LXV) | 57990 | (3R,4S)-4-(benzoyloxy)-3,4-dihydro-2H-pyran-3-yl benzoate | C19H16O5 | 详情 | 详情 | |
| (LXVI) | 57991 | (1S,2E)-1-(hydroxymethyl)-4-oxo-2-butenyl benzoate | C12H12O4 | 详情 | 详情 | |
| (LXVII) | 14689 | Methyl (triphenylphosphoranylidene)acetate; (methoxycarbonylmethylene)triphenylphosphorane；Methyl 2-(triphenyl-lambda(5)-phosphanylidene)acetate | 2605-67-6 | C21H19O2P | 详情 | 详情 |
| (LXVIII) | 57992 | (1S,2E,4E)-1-(hydroxymethyl)-6-methoxy-6-oxo-2,4-hexadienyl benzoate | C15H16O5 | 详情 | 详情 | |
| (LXIX) | 57993 | (1S)-1-(hydroxymethyl)-6-methoxy-6-oxohexyl benzoate | C15H20O5 | 详情 | 详情 | |
| (LXX) | 57994 | (1S)-6-methoxy-1-({[(4-methylphenyl)sulfonyl]oxy}methyl)-6-oxohexyl benzoate | C22H26O7S | 详情 | 详情 | |
| (LXXI) | 57995 | methyl 5-[(2S)oxiranyl]pentanoate | C8H14O3 | 详情 | 详情 | |
| (LXXII) | 16524 | bromo(vinyl)magnesium | 1826-67-1 | C2H3BrMg | 详情 | 详情 |
| (LXXIII) | 57996 | methyl (6S)-6-hydroxy-8-nonenoate | C10H18O3 | 详情 | 详情 | |
| (LXXIV) | 57997 | methyl (6S)-6-hydroxy-8-oxooctanoate | C9H16O4 | 详情 | 详情 |