A PRACTICAL SYNTHESIS OF AN ORALLY POTENT RENIN INHIBITOR, ISOPROPYL (2R,3S)-4-CYCLOHEXYL-2-HYDROXY-3-(N-[(2R)-2-MORPHOLINOCARBONYLMETHYL-3-(1-NAPHTHYL)PROPIONYL]-L-HISTIDYL)AMINOBUTYRATE

被引：10

作者：

HARADA, H

IYOBE, A

TSUBAKI, A

YAMAGUCHI, T

HIRATA, K

KAMIJO, T

IIZUKA, K

KISO, Y

机构：

[1] KISSEI PHARMACEUT CO LTD,CENT RES LABS,MATSUMOTO,NAGANO 399,JAPAN

[2] KYOTO PHARMACEUT UNIV,DEPT MED CHEM,YAMASHINA KU,KYOTO 607,JAPAN

来源：

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1990年 / 09期

关键词：

D O I：

10.1039/p19900002497

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The practical synthesis of an orally potent human renin inhibitor, isopropyl (2R,3S)-4-cyclohexyl-2-hydroxy-3-{N-[(2R)-2-morpholinocarbonylmethyl- 3-(1-naphthyl)propionyl]-L-histidyl}-aminobutyrate, is presented. Optically pure cyclohexylnorstatine isopropyl ester (P1-P1′ moiety) was diastereoselectively and simply prepared from L-phenylalanine methyl ester. In a one-pot reaction, N-[(2R)-2-morpholinocarbonylmethyl-3-(1-naphthyl) propionyl]-L-histidine methyl ester (P4-P2 moiety) was conveniently hydrolysed, protected with a Boc group attached to the side-chain imidazole function, and coupled with the cyclohexylnorstatine ester to give the optically pure target renin inhibitor.

引用

页码：2497 / 2500

页数：4

共 24 条

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