Issue 12, 2012

Fusarisetin A: scalable total synthesis and related studies

Abstract

Fusarisetin A (1) is a recently isolated natural product that displays an unprecedented chemical motif and remarkable bioactivities as a potent cancer migration inhibitor. We describe here our studies leading to an efficient and scalable total synthesis of 1. Essential to the strategy was the development of a new route for the formation of a trans-decalin moiety of this compound and the application of an oxidative radical cyclization (ORC) reaction that produces fusarisetin A (1) from equisetin (2) via a bio-inspired process. TEMPO-induced and metal/O2-promoted ORC reactions were evaluated. Biological screening in vitro confirms the reported potency of (+)-1. Importantly, ex vivo studies show that this compound is able to inhibit different types of cell migration. Moreover, the C5 epimer of (+)-1 was also identified as a potent cancer migration inhibitor, while (−)-1 and 2 were found to be significantly less potent. The optimized synthesis is applicable on gram scale and provides a solid platform for analogue synthesis and methodical biological study.

Graphical abstract: Fusarisetin A: scalable total synthesis and related studies

Supplementary files

Article information

Article type
Edge Article
Submitted
27 Jul 2012
Accepted
22 Aug 2012
First published
23 Aug 2012

Chem. Sci., 2012,3, 3378-3386

Fusarisetin A: scalable total synthesis and related studies

J. Xu, E. J. E. Caro-Diaz, M. H. Lacoske, Chao-I. Hung, C. Jamora and E. A. Theodorakis, Chem. Sci., 2012, 3, 3378 DOI: 10.1039/C2SC21308G

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