Issue 5, 2011
From the journal:

Organic & Biomolecular Chemistry

Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3

Yusuke Kasai,a   Nobuaki Matsumori,*a   Hiroyuki Ueno,a   Kenichi Nonomura,a   Shinya Yano,a   Murata Michio*a  and  Tohru Oishib  

* Corresponding authors

a Department of Chemistry, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka, Japan
E-mail: matsmori@chem.sci.osaka-u.ac.jp, murata@chem.sci.osaka-u.ac.jp
Fax: +81 6 6850-5790 +81 6 6850-5774
Tel: +81 6 6850-5789 +81 6 6850-5774

b Department of Chemistry, Graduate School of Sciences, Kyushu University, 6-10-1 Hakozaki, Higashi-ku, Fukuoka, Japan

Abstract

Two well-known antifungals, amphotericin B (AmB) and amphodinol 3 (AM3), are thought to exert antifungal activity by forming ion-permeable channels or pores together with sterol molecules. However, detailed molecular recognitions for AmB-sterol and AM3-sterol in lipid bilayers have yet to be determined. Toward 19F NMR-based investigation of the molecular recognition underlying their potent antifungal activity, we synthesized 6-fluoro-ergosterol in five steps via ring opening of (5α,6α)-epoxide of ergosterol acetate with using novel combination of TiF4 and n-Bu4N+Ph3SiF2−. Then we evaluated its activity of promoting pore formation of AmB and AM3, and found that pore formation of AmB was barely promoted by 6-F-ergosterol in clear contrast to the dramatic promotion effect of unmodified ergosterol, whereas AM3 activity was markedly enhanced in the presence of 6-F-ergosterol, which was comparable to that of unmodified ergosterol. These results indicate that the introduction of an F atom at C6 position of ergosterol plays an inhibitory role in interacting with AmB, but it is not the case with AM3.

Graphical abstract: Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3

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Article information

DOI
https://doi.org/10.1039/C0OB00685H
Article type
Paper
Submitted
07 Sep 2010
Accepted
22 Nov 2010
First published
11 Jan 2011

Org. Biomol. Chem., 2011,9, 1437-1442

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Synthesis of 6-F-ergosterol and its influence on membrane-permeabilization of amphotericin B and amphidinol 3

Y. Kasai, N. Matsumori, H. Ueno, K. Nonomura, S. Yano, M. Michio and T. Oishi, Org. Biomol. Chem., 2011, 9, 1437 DOI: 10.1039/C0OB00685H

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