title: 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/O(2)-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 C(5) 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.
authors.affiliation: Department of Chemistry & Biochemistry, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0358, USA.
authors.forename: Jing
authors.initials: J
authors.lastname: Xu
authors.forename: Eduardo J E
authors.initials: EJ
authors.lastname: Caro-Diaz
authors.forename: Michelle H
authors.initials: MH
authors.lastname: Lacoske
authors.forename: Chao-I
authors.initials: CI
authors.lastname: Hung
authors.forename: Colin
authors.initials: C
authors.lastname: Jamora
authors.forename: Emmanuel A
authors.initials: EA
authors.lastname: Theodorakis