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.
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页码：4049 / 4053
页数：5
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