ENANTIOSELECTIVE SYNTHESIS OF CALCIUM-CHANNEL BLOCKERS OF THE DILTIAZEM GROUP

被引：117

作者：

SCHWARTZ, A

MADAN, PB

MOHACSI, E

OBRIEN, JP

TODARO, LJ

COFFEN, DL

机构：

[1] Roche Research Center, Hoffmann-La Roche Inc., Nutley

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1992年 / 57卷 / 03期

关键词：

D O I：

10.1021/jo00029a013

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A lipase-catalyzed kinetic resolution of racemic trans-2-phenylcyclohexanol readily provides the (-)-1R,2S enantiomer. This alcohol is employed as its chloroacetate 10a in a chiral auxiliary-induced asymmetric Darzens glycidic ester condensation with p-anisaldehyde (9). Crystallization of the Darzens product affords enantiomerically pure (1R,2S)-2-phenylcyclohexyl (1R,2S)-2-(p-methoxyphenyl)glycidate (11), the structure of which was established by X-ray crystallography. The use of this glycidic ester in syntheses of diltiazem (1) and naltiazem (8), members of the diltiazem group of calcium channel blockers, provides these drug substances directly in enantiomerically pure form.

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页码：851 / 856

页数：6

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