【结 构 式】 |
【分子编号】57971 【品名】2-[(1S)-2-oxocyclohexyl]ethyl acetate 【CA登记号】 |
【 分 子 式 】C10H16O3 【 分 子 量 】184.23524 【元素组成】C 65.19% H 8.75% O 26.05% |
合成路线1
该中间体在本合成路线中的序号:(XLIII)A different strategy was based on the enantioselective oxidation of a cyclohexanone derivative by enzymic Baeyer-Villiger reaction. Keto ester (XXXVIII) was protected as the ethylene ketal (XXXIX) and subsequently reduced to alcohol (XL) using LiAlH4. Acetylation of alcohol (XL) to acetate (XLI), followed by acidic ketal hydrolysis afforded cyclohexanone (XLII) (9,10). The racemic ketone (XLII) was then subjected to oxidative cleavage by monooxigenase 2 obtained from Pseudomonas putida to furnish the (R)-lactone (XLIV) along with unreacted (S)-cyclohexanone (XLIII) (9-11). The use of cyclohexanone monooxigenase from Acinetobacter NCIMB 9871 has also been reported for this reaction (12). Methanolysis of lactone (XLIV) in the presence of NaOMe gave rise to the (R)-dihydroxy ester (XLV). Inversion of the configuration of (XLV) was accomplished by Mitsunobu coupling with p-nitrobenzoic acid (XLVI) to produce the (S)-p-nitrobenzoate ester (XLVII). Smooth hydrolysis of ester (XLVII) provided methyl (S)-6,8-dihydroxyoctanoate (XLVIII), which was processed through intermediates (XLIX) and (L), as for the isopropyl (X) (Scheme 29605101a) and ethyl (XXIX) (Scheme 29605103a) homologues, to afford the title compound.
【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 . |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(XXXVIII) | 57966 | Ethyl 2-cyclohexanone acetate; Ethyl 2-oxocyclohexane acetate | 24731-17-7 | C10H16O3 | 详情 | 详情 |
(XXXIX) | 57967 | ethyl 2-(1,4-dioxaspiro[4.5]dec-6-yl)acetate | C12H20O4 | 详情 | 详情 | |
(XL) | 57968 | 2-(1,4-dioxaspiro[4.5]dec-6-yl)-1-ethanol | C10H18O3 | 详情 | 详情 | |
(XLI) | 57969 | 2-(1,4-dioxaspiro[4.5]dec-6-yl)ethyl acetate | C12H20O4 | 详情 | 详情 | |
(XLII) | 57970 | 2-(2-oxocyclohexyl)ethyl acetate | C10H16O3 | 详情 | 详情 | |
(XLIII) | 57971 | 2-[(1S)-2-oxocyclohexyl]ethyl acetate | C10H16O3 | 详情 | 详情 | |
(XLIV) | 57972 | 2-[(2R)-7-oxooxepanyl]ethyl acetate | C10H16O4 | 详情 | 详情 | |
(XLV) | 57973 | methyl (6R)-6,8-dihydroxyoctanoate | C9H18O4 | 详情 | 详情 | |
(XLVI) | 18119 | 4-nitrobenzoic acid; p-nitrobenzoic acid | 62-23-7 | C7H5NO4 | 详情 | 详情 |
(XLVII) | 57974 | (1S)-6-methoxy-1-{2-[(4-nitrobenzoyl)oxy]ethyl}-6-oxohexyl 4-nitrobenzoate | C23H24N2O10 | 详情 | 详情 | |
(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 |