Bioisosteric Exchange of Csp3-Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of AtpeninA5 Analogues

被引：18
|
作者：
Krautwald, Simon [1 ]
Nilewski, Christian [1 ]
Mori, Mihoko [2 ,3 ]
Shiomi, Kazuro [2 ,3 ]
Omura, Satoshi [2 ,3 ]
Carreira, Erick M. [1 ]
机构：
[1] ETH, Organ Chem Lab, HCI H335, Vladimir Prelog Weg 3, CH-8093 Zurich, Switzerland
[2] Kitasato Univ, Kitasato Inst Life Sci, Dept Drug Discovery Sci, Minato Ku, 5-9-1 Shirokane, Tokyo 1088641, Japan
[3] Kitasato Univ, Grad Sch Infect Control Sci, Minato Ku, 5-9-1 Shirokane, Tokyo 1088641, Japan
来源：
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION | 2016年 / 55卷 / 12期
基金：
欧洲研究理事会;
关键词：
antifungal agents; atpenins; bioisosterism; chlorinated natural products; inhibition of respiratory chain; SUCCINATE-UBIQUINONE OXIDOREDUCTASE; MITOCHONDRIAL COMPLEX-II; ENANTIOSELECTIVE TOTAL-SYNTHESIS; PRACTICAL CHIRAL AUXILIARY; ASYMMETRIC EPOXIDATION; TRICHODERMA-HARZIANUM; MEDICINAL CHEMISTRY; ISOSTERIC ANALOGS; ALLYLIC ALCOHOLS; PENICILLIUM SP;
D O I：
10.1002/anie.201511672
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, atpeninA5, are described. These analogues were selected on the basis of ClCH3 or H3CCl exchanges in the side-chain of atpeninA5. The interchange of chloro and methyl substituents led to complexII inhibitors with equal IC50 values. This suggests that ClMe bioisosteric exchange can be realized in aliphatic settings.
引用
收藏
页码：4049 / 4053
页数：5
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