STUDIES IN THE SYNTHESIS OF THE THROMBOXANE RECEPTOR ANTAGONIST EP-092 AND ITS ENANTIOMERS

被引:37
作者
GARLAND, RB
MIYANO, M
PIREH, D
CLARE, M
FINNEGAN, PM
SWENTON, L
机构
[1] Searle Research and Development, Division of G. D. Searle & Co., Skokie, Illinois 60077
关键词
D O I
10.1021/jo00310a017
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
An improved synthesis of EP 092 was developed. Resolution of an early intermediate was achieved by using butane-2(R),3(R)-diol ketals. Both enantiomers of EP 092 were found to possess platelet aggregation inhibition activity, but the l enantiomer was much more potent. A new synthesis was devised for the enantiomers starting from known enantiomerically pure chiral intermediates. It was found that the symmetry of these starting materials permitted the facile inversion of one enantiomer into the other via the Wharton reaction. Molecular mechanics studies provided a basis for explaining partial kinetic resolution during ketal formation as well as differences in the ease of Baeyer-Villiger oxidation of epimeric a-methyl ketones. © 1990, American Chemical Society. All rights reserved.
引用
收藏
页码:5854 / 5861
页数:8
相关论文
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