Synthesis of capuramycin and its analogues via a Ferrier-type I reaction and their biological evaluation

Shintaro Kusaka; Kazuki Yamamoto; Motoko Shinohara; Yusuke Minato; Satoshi Ichikawa

doi:10.1016/j.bmc.2022.117011

Synthesis of capuramycin and its analogues via a Ferrier-type I reaction and their biological evaluation

Bioorg Med Chem. 2022 Nov 1:73:117011. doi: 10.1016/j.bmc.2022.117011. Epub 2022 Sep 26.

Authors

Shintaro Kusaka¹, Kazuki Yamamoto², Motoko Shinohara³, Yusuke Minato³, Satoshi Ichikawa⁴

Affiliations

¹ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
² Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan.
³ Department of Microbiology, Fujita Health University School of Medicine, 1-98, Dengakugakubo, Kutsukake-cho, Toyoake, Aichi 470-1192, Japan.
⁴ Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Center for Research and Education on Drug Discovery, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan; Global Station for Biosurfaces and Drug Discovery, Global Institution for Collaborative Research and Education (GI-CoRE), Hokkaido University, Kita-12, Nishi-6, Kita-ku, Sapporo 060-0812, Japan. Electronic address: ichikawa@pharm.hokudai.ac.jp.

PMID: 36191548
DOI: 10.1016/j.bmc.2022.117011

Abstract

The total synthesis of capuramycin (1), which is a promising anti-tubercular antibiotics, has been accomplished using Ferrier-type I reaction as a key step. This total synthesis is an alternative approach to the synthesis of capuramycin and its analogues. The 3'-O-demethyl analogue (2), which exhibits an equivalent antibacterial activity as capuramycin (1) against Mycobacterium smegmatis and Mycobacterium avium, is suggested to have potential as a lead structure of capuramycin analogues because 2 is more accessible from a synthetic view point.

Keywords: Antibacterial; MraY; Natural product; Nucleoside; Structure-activity relationship.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aminoglycosides* / chemistry
Anti-Bacterial Agents / chemistry
Mycobacterium smegmatis*
Structure-Activity Relationship

Substances

Aminoglycosides
Anti-Bacterial Agents
capuramycin