An efficient synthetic method for Z-fluoroalkene dipeptide isosteres: Application to the synthesis of the dipeptide isostere of Sta-Ala

被引：37

作者：

Nakamura, Yuko

Okada, Midori

Koura, Minoru

Tojo, Manabu

Saito, Akio

Sato, Azusa

Taguchi, Takeo

机构：

[1] Tokyo Univ Pharm & Life Sci, Tokyo 1920392, Japan

[2] Tokyo Womens Med Univ, Shinjuku Ku, Tokyo 1628666, Japan

来源：

JOURNAL OF FLUORINE CHEMISTRY | 2006年 / 127卷 / 4-5期

关键词：

fluoroalkene; difuoroalkenoate; organocopper; dipeptide isostere; pepstatin;

D O I：

10.1016/j.jfluchem.2005.11.016

中图分类号：

O61 [无机化学];

学科分类号：

070301 ; 081704 ;

摘要：

Reaction of gamma,gamma-difluoro-alpha,beta-enoates having a delta-hydroxyl group with trialkylaluminum (R3Al) was found to be promoted by CuI.2LiCl and to proceed in SN2' manner giving rise to the alpha-alkylated (Z)-gamma-fluoro-beta, gamma-enoates, while reductive defluorination of gamma,gamma-difluoro-alpha,beta-enoates with Me2CuLi followed by reaction with alkyl halides provided the corresponding (Z)-alpha-alkylated products in high yields. The latter reaction was applied to the preparation of the dipeptide (Z)-fluoroalkene isostere of Sta-Ala, which is the central dipeptide unit in Pepstatin, a natural inhibitor of aspartate proteases. (C) 2005 Elsevier B.V. All rights reserved.

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页码：627 / 636

页数：10

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