Total Synthesis of "Aliskiren": The First Renin Inhibitor in Clinical Practice for Hypertension

被引：31

作者：

Hanessian, Stephen ^{[1
]}

Guesne, Sebastien ^{[1
]}

Chenard, Etienne ^{[1
]}

机构：

[1] Univ Montreal, Dept Chem, Montreal, PQ H3C 3J7, Canada

来源：

ORGANIC LETTERS | 2010年 / 12卷 / 08期

基金：

加拿大自然科学与工程研究理事会;

关键词：

ANGIOTENSIN-ALDOSTERONE SYSTEM; RING-CLOSING METATHESIS; CONVERGENT SYNTHESIS; DISCOVERY;

D O I：

10.1021/ol100427v

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

We report a "macrocycle route" toward aliskiren, a drug presently marketed for the treatment of hypertension, using a highly stereocontrolled approach starting from a common "isopropyl chiron". Highlights of the synthesis include a challenging RCM reaction to produce a nine-membered unsaturated lactone, a highly stereoselective catalytic Du Bois aziridination, and a regio- and diastereoselective aziridine ring-opening to a vicinal amino alcohol.

引用

页码：1816 / 1819

页数：4

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