title: Bioisosteric Exchange of Csp3 -Chloro and Methyl Substituents: Synthesis and Initial Biological Studies of Atpenin A5 Analogues.
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.
authors.affiliation: Laboratorium für Organische Chemie, HCI H335, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
authors.forename: Simon
authors.initials: S
authors.lastname: Krautwald
authors.affiliation: Laboratorium für Organische Chemie, HCI H335, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Nilewski
authors.affiliation: Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Mihoko
authors.initials: M
authors.lastname: Mori
authors.affiliation: Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan. shiomi@lisci.kitasato-u.ac.jp.
authors.forename: Kazuro
authors.initials: K
authors.lastname: Shiomi
authors.affiliation: Department of Drug Discovery Sciences, Kitasato Institute for Life Sciences and Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo, 108-8641, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ōmura
authors.affiliation: Laboratorium für Organische Chemie, HCI H335, Eidgenössische Technische Hochschule Zürich, Vladimir-Prelog-Weg 3, 8093, Zürich, Switzerland. carreira@org.chem.ethz.ch.
authors.forename: Erick M
authors.identifier: http://orcid.org/0000-0003-1472-490X
authors.initials: EM
authors.lastname: Carreira
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D011728:Pyridones / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000935:Antifungal Agents; D011728:Pyridones; C058278:atpenin A5
keywords: antifungal agents; atpenins; bioisosterism; chlorinated natural products; inhibition of respiratory chain