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【结 构 式】 
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【分子编号】42367 【品名】benzyl 2-[(2S)oxiranyl]ethyl ether; (2S)-2-[2-(benzyloxy)ethyl]oxirane 【CA登记号】 |
【 分 子 式 】C11H14O2 【 分 子 量 】178.23096 【元素组成】C 74.13% H 7.92% O 17.95% |
合成路线1
该中间体在本合成路线中的序号：(I)Synthesis of intermediate (VII): The condensation of epoxide (I) with vinyl lithium (II) by means of CuCN gives the allylic alcohol (III), which is epoxidated to epoxide (IV). The silylation of (IV) with TBDPSCl and imidazole yields the silyl ether (V), which is condensed with 1,3-dithiane (VI) by means of n-BuLi and protected with TBDPSCl as before to afford the desired intermediate (VII).
| 【1】 Guo, J.; et al.; Total synthesis of altohyrtin A (spongistatin 1): Part 1. Angew Chem. Int Ed Engl 1998, 37, 1-2, 187. |
| 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) | 42367 | benzyl 2-[(2S)oxiranyl]ethyl ether; (2S)-2-[2-(benzyloxy)ethyl]oxirane | C11H14O2 | 详情 | 详情 | |
| (II) | 42368 | vinyllithium | 917-57-7 | C2H3Li | 详情 | 详情 |
| (III) | 42369 | (3R)-1-(benzyloxy)-5-hexen-3-ol | C13H18O2 | 详情 | 详情 | |
| (IV) | 42370 | (2S)-4-(benzyloxy)-1-[(2S)oxiranyl]-2-butanol | C13H18O3 | 详情 | 详情 | |
| (V) | 42371 | benzyl (3S)-3-[[tert-butyl(diphenyl)silyl]oxy]-4-[(2S)oxiranyl]butyl ether; ([(1S)-3-(benzyloxy)-1-[(2S)oxiranylmethyl]propyl]oxy)(tert-butyl)diphenylsilane | C29H36O3Si | 详情 | 详情 | |
| (VI) | 42372 | 1,3-dithiane | 505-23-7 | C4H8S2 | 详情 | 详情 |
| (VII) | 42373 | benzyl (3S,5S)-3,5-bis[[tert-butyl(diphenyl)silyl]oxy]-6-(1,3-dithian-2-yl)hexyl ether; (5S,7S)-5-[2-(benzyloxy)ethyl]-7-(1,3-dithian-2-ylmethyl)-2,2,10,10-tetramethyl-3,3,9,9-tetraphenyl-4,8-dioxa-3,9-disilaundecane | C49H62O3S2Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XXIV)A further procedure for the preparation of the key intermediate (XIII) utilized the chiral starting material (S)-4-benzyloxy-1,2-butanediol (XIX), easily accessible from (S)-malic acid. Inversion of the configuration of (XIX) was accomplished via formation of dimesylate (XX), followed by displacement with potassium acetate in refluxing Ac2O. The resultant diacetate (XXI) was hydrolyzed to the required (R)-diol (XXII) by treatment with K2CO3 in MeOH. Conversion of (XXII) into epoxide (XXIV) was performed through the benzylidene ketal (XXIII), following the reported procedure for the corresponding (S)-enantiomer. Copper(I)-catalyzed addition of 3-butenylmagnesium bromide (XXV) to epoxide (XXIV) furnished alcohol (XXVI), which was further protected as the benzyl ether (XXVII). Hydroboration of olefin (XXVII) with in situ generated disiamylborane, followed by oxidative work-up gave rise to the primary alcohol (XXVIII). This was oxidized with pyridinium dichromate to the carboxylic acid (XXIX), which was further esterified by means of methanolic HCl to afford ester (XXX). Then, catalytic hydrogenolysis of the di(benzyloxy) ester (XXX) yielded the target intermediate dihydroxyester (XIII).
| 【1】 Brookes, M.H.; et al.; Syntheses of alpha-(R)- and alpha-(S)-lipoic acid from (S)-malic acid. J Chem Soc - Perkins Trans I 1988, 1, 9. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (XIII) | 57977 | methyl (6S)-6,8-dihydroxyoctanoate | C9H18O4 | 详情 | 详情 | |
| (XIX) | 58043 | (2S)-4-(benzyloxy)-1,2-butanediol | C11H16O3 | 详情 | 详情 | |
| (XX) | 58044 | (2S)-4-(benzyloxy)-2-[(methylsulfonyl)oxy]butyl methanesulfonate | C13H20O7S2 | 详情 | 详情 | |
| (XXI) | 58045 | (2R)-2-(acetyloxy)-4-(benzyloxy)butyl acetate | C15H20O5 | 详情 | 详情 | |
| (XXII) | 58052 | (2R)-4-(benzyloxy)-1,2-butanediol | C11H16O3 | 详情 | 详情 | |
| (XXIII) | 58046 | (4R)-4-[2-(benzyloxy)ethyl]-2-phenyl-1,3-dioxolane; benzyl 2-[(4R)-2-phenyl-1,3-dioxolan-4-yl]ethyl ether | C18H20O3 | 详情 | 详情 | |
| (XXIV) | 42367 | benzyl 2-[(2S)oxiranyl]ethyl ether; (2S)-2-[2-(benzyloxy)ethyl]oxirane | C11H14O2 | 详情 | 详情 | |
| (XXV) | 35896 | bromo(3-butenyl)magnesium | 7103-09-5 | C4H7BrMg | 详情 | 详情 |
| (XXVI) | 58047 | (3S)-1-(benzyloxy)-7-octen-3-ol | C15H22O2 | 详情 | 详情 | |
| (XXVII) | 58048 | 1-({[(3S)-3-(benzyloxy)-7-octenyl]oxy}methyl)benzene; benzyl (1S)-1-[2-(benzyloxy)ethyl]-5-hexenyl ether | C22H28O2 | 详情 | 详情 | |
| (XXVIII) | 58049 | (6S)-6,8-bis(benzyloxy)-1-octanol | C22H30O3 | 详情 | 详情 | |
| (XXIX) | 58050 | (6S)-6,8-bis(benzyloxy)octanoic acid | C22H28O4 | 详情 | 详情 | |
| (XXX) | 58051 | methyl (6S)-6,8-bis(benzyloxy)octanoate | C23H30O4 | 详情 | 详情 |