Total Synthesis of Amphidinol 3: A General Strategy for Synthesizing Amphidinol Analogues and Structure-Activity Relationship Study

Yuma Wakamiya, Makoto Ebine, Nobuaki Matsumori, Tohru Oishi

Research output: Contribution to journalArticle

Abstract

Amphidinol 3 (AM3) is a potent antifungal produced by the dinoflagellate Amphidinium klebsii. It was difficult to determine the absolute configuration of AM3 by using the scarce natural product due to the presence of numerous stereogenic centers on the acyclic carbon chain. Since the absolute configuration was partially determined on the basis of insufficient evidence, the originally proposed structure has been revised three times. Although recent progress on structure determination by computational analysis is remarkable, total synthesis is still the most reliable way to confirm structures. The first total synthesis of AM3 was achieved via expeditious assembly of three components in five steps, confirming the revised structure of AM3 after more than 20 years since its first discovery. The established synthetic route would be a general strategy for synthesizing amphidinol congeners. An artificial and simplified analogue of AM3, which elicited antifungal activity comparable to that of AM3, was designed and synthesized. This is the first example of a biologically active artificial analogue possessing a shorter polyol moiety, providing insight on the antifungal mode-of-action.

Original languageEnglish
Pages (from-to)3472-3478
Number of pages7
JournalJournal of the American Chemical Society
Volume142
Issue number7
DOIs
Publication statusPublished - Feb 19 2020

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this