Design, Synthesis, and Antifungal Activity of 16,17-Dihydroheronamide C and ent-Heronamide C

Naoki Kanoh; Ryusei Terashima; Hiromichi Nishiyama; Yuta Terajima; Shota Nagasawa; Yusuke Sasano; Yoshiharu Iwabuchi; Hiroaki Saito; Syusuke Egoshi; Kosuke Dodo; Mikiko Sodeoka; Chengqian Pan; Yoshinobu Ikeuchi; Shinichi Nishimura; Hideaki Kakeya

doi:10.1021/acs.joc.1c01761

Design, Synthesis, and Antifungal Activity of 16,17-Dihydroheronamide C and ent-Heronamide C

J Org Chem. 2021 Dec 3;86(23):16249-16258. doi: 10.1021/acs.joc.1c01761. Epub 2021 Nov 16.

Authors

Affiliations

¹ School of Pharmacy and Pharmaceutical Sciences, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
² Institute of Medicinal Chemistry, Hoshi University, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
³ Graduate School of Pharmaceutical Sciences, Tohoku University, 6-3 Aza-aoba, Aramaki, Aoba-ku, Sendai 980-8578, Japan.
⁴ Faculty of Pharmaceutical Sciences, Hokuriku University, 3 Kanagawamachi, Kanazawa, Ishikawa 920-1181, Japan.
⁵ Synthetic Organic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, 2-1 Hirosawa, Wako, Saitama 351-0198, Japan.
⁶ Graduate School of Pharmaceutical Sciences, Kyoto University, 46-29 Shimo-Adachi-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.
⁷ Department of Biotechnology, Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo 113-8657, Japan.

PMID: 34784214
DOI: 10.1021/acs.joc.1c01761

Abstract

16,17-Dihydroheronamide C (8) and ent-heronamide C (ent-1) were designed as probes for the mode-of-action analysis of heronamide C (1). These molecules were synthesized by utilizing a highly modular strategy developed in the preceding paper. The evaluation of the antifungal activity of these compounds revealed the exceptional importance of the C16-C17 double bond for the antifungal activity of heronamide C and the existence of chiral recognition between heronamide C (1) and cell membrane components.

Publication types

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

MeSH terms

Antifungal Agents* / pharmacology
Lactams, Macrocyclic
Structure-Activity Relationship

Substances

Antifungal Agents
Lactams, Macrocyclic
heronamide C