【结 构 式】 |
【分子编号】38667 【品名】(1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(butylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate 【CA登记号】 |
【 分 子 式 】C29H49NO5 【 分 子 量 】491.7118 【元素组成】C 70.84% H 10.04% N 2.85% O 16.27% |
合成路线1
该中间体在本合成路线中的序号:(V)The reaction of Lovastatin (I) with refluxing butylamine gives the N-butylamide (II), which is silylated with TBDMS-Cl and imidazole to yield the bis(silyl) ether (III). The careful methylation of (III) with MeI (only 1.5 mol) and lithium pyrrolidide in THF at -10 C affords a high yield of 2,2-dimethylbutyrate (IV) avoiding the methylation of the amide nitrogen. The desilylation of (IV) with MsOH in methanol gives the dihydroxyamide (V), which is treated successively with NaOH in methanol/water, with HCl, and finally with ammonia in methanol to give the ammonium salt (VI). Finally, this compound is cyclized by heating at 100 C in toluene to afford the target simvastatin.
【1】 Askin, D.; et al.; Synthesis of synvinolin: Extremely high conversion alkylation of an ester enolate. J Org Chem 1991, 56, 16, 4929. |
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) | 64415 | (1S,3R,7S,8S,8aR)-8-{2-[(2R,4R)-4-hydroxy-6-oxotetrahydro-2H-pyran-2-yl]ethyl}-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate | C24H36O5 | 详情 | 详情 | |
(II) | 38664 | (1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(butylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate | C28H47NO5 | 详情 | 详情 | |
(III) | 38665 | (1S,3R,7S,8S,8aR)-8-((3R,5R)-7-(butylamino)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl (2S)-2-methylbutanoate | C40H75NO5Si2 | 详情 | 详情 | |
(IV) | 38666 | (1S,3R,7S,8S,8aR)-8-((3R,5R)-7-(butylamino)-3,5-bis[[tert-butyl(dimethyl)silyl]oxy]-7-oxoheptyl)-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate | C41H77NO5Si2 | 详情 | 详情 | |
(V) | 38667 | (1S,3R,7S,8S,8aR)-8-[(3R,5R)-7-(butylamino)-3,5-dihydroxy-7-oxoheptyl]-3,7-dimethyl-1,2,3,7,8,8a-hexahydro-1-naphthalenyl 2,2-dimethylbutanoate | C29H49NO5 | 详情 | 详情 | |
(VI) | 37616 | ammonium (3R,5R)-7-[(1S,2S,6R,8S,8aR)-8-[(2,2-dimethylbutanoyl)oxy]-2,6-dimethyl-1,2,6,7,8,8a-hexahydro-1-naphthalenyl]-3,5-dihydroxyheptanoate | C25H43NO6 | 详情 | 详情 |