Cyclopropanecarboxylic acid esters as potential prodrugs with enhanced hydrolytic stability

被引：32

作者：

Bender, David M. ^{[1
]}

Peterson, Jeffrey A. ^{[1
]}

McCarthy, James R. ^{[1
]}

Gunaydin, Hakan ^{[2
]}

Takano, Yu ^{[2
]}

Houk, K. N. ^{[2
]}

机构：

[1] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA

[2] Univ Calif Los Angeles, Dept Chem & Biochem, Los Angeles, CA 90095 USA

来源：

ORGANIC LETTERS | 2008年 / 10卷 / 03期

关键词：

D O I：

10.1021/ol702892e

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

Esters of cyclopropanecarboxylic acid demonstrate a substantial increase in stability under both acid- and base-catalyzed hydrolytic conditions. Comparison of the stability of valacyclovir 13 with the cyclopropane analogue 14 shows that at 40 degrees C and pH 6 the half-life of 14 is >300 h while the value for 13 is 69.7 h. CBS-QB3 calculations on isodesmic reactions for transfer of groups from an alkane to an ester show that a cyclopropyl group provides hyperconjugative stabilization.

引用

页码：509 / 511

页数：3

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