SYNTHESIS OF SYNVINOLIN - EXTREMELY HIGH CONVERSION ALKYLATION OF AN ESTER ENOLATE

被引：36

作者：

ASKIN, D

VERHOEVEN, TR

LIU, TMH

SHINKAI, I

机构：

[1] Department of Process Research, Merck, Sharp and Dohme Research Laboratories, Rahway, New Jersey 07065

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1991年 / 56卷 / 16期

关键词：

D O I：

10.1021/jo00016a023

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A efficient process for the commercial preparation of the therapeutically important cholesterol lowering drug synvinolin (2: simvastatin, ZOCOR) from mevinolin (1: lovastatin, MEVACOR) is reported. The synthesis relies upon deactivation of the delta-lactone carbonyl toward enolization via conversion to the bis[(tert-butyldimethylsilyl)oxy] butylamide 7. An extremely high conversion (99.7%) ester enolate alkylation of 7 affords 8 and 9. Subsequent desilylation and intramolecularly assisted basic amide hydrolysis in the presence of the dimethylbutyrate ester moiety yields 12, which is lactonized to 2. The overall yield from 1 to 2 is 86%.

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页码：4929 / 4932

页数：4

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