Issue 3, 2021

Total synthesis and complete configurational assignment of amphirionin-2

Abstract

Amphirionin-2 is a linear polyketide metabolite that exhibits potent and selective cytotoxic activity against certain human cancer cell lines. We disclose herein the first total synthesis of amphirionin-2 and determination of its absolute configuration. Our synthesis featured an extensive use of cobalt-catalyzed Mukaiyama-type cyclization of γ-hydroxy olefins for stereoselective formation of all the tetrahydrofuran rings found in the natural product, and a late-stage Stille-type coupling for convergent assembly of the entire carbon backbone. Four candidate diastereomers of amphirionin-2 were synthesized in a unified, convergent manner, and their spectroscopic/chromatographic properties were compared with those of the authentic material. The present study culminated in the reassignment of the C5/C7 relative configuration, assignment of the C12/C18 relative configuration, and determination of the absolute configuration of amphirionin-2.

Graphical abstract: Total synthesis and complete configurational assignment of amphirionin-2

Supplementary files

Article information

Article type
Edge Article
Submitted
02 Nov. 2020
Accepted
19 Nov. 2020
First published
20 Nov. 2020
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 872-879

Total synthesis and complete configurational assignment of amphirionin-2

S. Kato, D. Mizukami, T. Sugai, M. Tsuda and H. Fuwa, Chem. Sci., 2021, 12, 872 DOI: 10.1039/D0SC06021F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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