Enantioselective synthesis of the pyrrolidine core of endothelin antagonist ABT-627 (Atrasentan) via 1,2-oxazines

被引：36

作者：

Buchholz, M ^{[1
]}

Reissig, HU ^{[1
]}

机构：

[1] Free Univ Berlin, Inst Chem Organ Chem, D-14195 Berlin, Germany

来源：

EUROPEAN JOURNAL OF ORGANIC CHEMISTRY | 2003年 / 2003卷 / 18期

关键词：

asymmetric synthesis; hydrogenations; inhibitors; ring contraction; nitrogen heterocycles;

D O I：

10.1002/ejoc.200300234

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Diastereoselective syntheses of the pyrrolidine core 6a of the endothelin antagonist ABT-627 (Atrasentan) either as a racemic mixture or as an enantiopure compound are presented. The crucial steps of these syntheses utilized the highly diastereoselective conjugate addition of 1,3-benzodioxol-5-yl-lithium to racemic 6H-1,2-oxazine 3 or enantiopure 6H-1,2-oxazines 7 or 8, followed by trapping with ethyl cyanoformate (Mander's reagent). The resulting 5,6-dihydro-4H-1,2-oxazines were transformed into the 2,3,4-trisubstituted pyrrolidine 6a. (C) Wiley-VCH Verlag GmbH Co.

引用

页码：3524 / 3533

页数：10

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