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

Yusuke Kasai, Nobuaki Matsumori, Hiroyuki Ueno, Kenichi Nonomura, Shinya Yano, Murata Michio, Tohru Oishi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

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-Bu 4N+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.

Original languageEnglish
Pages (from-to)1437-1442
Number of pages6
JournalOrganic and Biomolecular Chemistry
Volume9
Issue number5
DOIs
Publication statusPublished - Mar 1 2011

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

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