Bioisosteric Exchange of Csp3 ‐Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues. Issue 12 (17th February 2016)

• Record Type: Journal Article
• Authors: Krautwald, Simon; Nilewski, Christian; Mori, Mihoko; Shiomi, Kazuro; Ōmura, Satoshi; Carreira, Erick M.
• Is Part Of: Angewandte Chemie international edition. Volume 55:Issue 12(2016)
• Page Start: 4049
• Page End: 4053
• Publication Date: 2016-02-17
• Subjects: antifungal agents -- atpenins -- bioisosterism -- chlorinated natural products -- inhibition of respiratory chain; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201511672
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: Asymmetric synthesis and initial biological studies of two analogues of a naturally occurring chlorinated antifungal agent, atpenin A5, are described. These analogues were selected on the basis of Cl→CH3 or H3 C→Cl exchanges in the side‐chain of atpenin A5. The interchange of chloro and methyl substituents led to complex II inhibitors with equal IC50 values. This suggests that Cl↔Me bioisosteric exchange can be realized in aliphatic settings. Abstract : Changing places : Asymmetric synthesis and initial biological studies of two analogues of the complex II inhibitor atpenin A5 are reported. Bioisosteric exchange of ‐chloro and methyl substituents resulted in analogues with essentially identical biological activity as inhibitors of complex II.