TOTAL SYNTHESIS OF DIHYDROMEVINOLIN AND A SERIES OF RELATED 3-HYDROXY-3-METHYLGLUTARYL COENZYME-A REDUCTASE INHIBITORS

被引：23

作者：

BLACKWELL, CM ^{[1
]}

DAVIDSON, AH ^{[1
]}

LAUNCHBURY, SB ^{[1
]}

LEWIS, CN ^{[1
]}

MORRICE, EM ^{[1
]}

REEVE, MM ^{[1
]}

ROFFEY, JAR ^{[1
]}

TIPPING, AS ^{[1
]}

TODD, RS ^{[1
]}

机构：

[1] BRITISH BIOTECHNOL LTD,DEPT MED CHEM,WATLINGTON RD,OXFORD OX4 5LY,ENGLAND

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1992年 / 57卷 / 21期

关键词：

D O I：

10.1021/jo00047a011

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The natural product dihydromevinolin, 2, and a series of structurally related 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, 3-6, have been synthesized. The key features are an intramolecular Diels-Alder reaction to form a functionalized decalin skeleton with six asymmetric centers in a stereocontrolled manner, the selective manipulation of the functional groups, and an improved method for the introduction and elaboration of the delta-lactone portion. Analogue 6 was approximately 10-fold more potent than 2 as an inhibitor and was produced in multigram quantities.

引用

页码：5596 / 5606

页数：11

共 52 条

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