Synthesis of (+)-Fusarisetin A

Erick M. Carreira; Adrien Joliton

doi:10.1055/s-0033-1340357

Synfacts, Table of Contents

Synfacts 2014; 10(1): 0008
DOI: 10.1055/s-0033-1340357

Synthesis of Natural Products and Potential Drugs

Synthesis of (+)-Fusarisetin A

Contributor(s):

Erick M. Carreira

,

Adrien Joliton

Abstract

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Huang J, Fang L, Long R, Shi L.-L, Shen H.-J, Li C.-C, * Yang Z. * Peking University Shenzhen Graduate School and Peking University, Beijing, P. R. of China
Asymmetric Total Synthesis of (+)-Fusarisetin A via the Intramolecular Pauson–Khand Reaction.

Org. Lett. 2013;
15: 4018-4021

Key words

fusarisetin A - intramolecular Pauson–Khand reaction - cobalt - Dieckmann condensation

Significance

Isolated in 2011 from the soil fungus Fusarium sp. FN080326, fusarisetin A has gained considerable attention because of its unprecedented molecular structure and its striking bioactivity. Fusarisetin A exhibits a complex 6,6,5,5,5-fused pentacyclic ring system containing ten stereocenters. Moreover, this natural product displays potent inhibition of acinar morphogenesis, cell migration, and invasion in MDA-MB-231 breast cancer cells, without apparent cytotoxicity. Li, Yang, and co-workers report a total synthesis of (+)-fusarisetin A based on a stereoselective intramolecular Pauson–Khand reaction for the construction of the 6,6,5-tricyclic moiety.

Comment

After screening of conditions, the authors identified the Co₂(CO)₈-mediated Pauson–Khand reaction as the most efficient method for the stereoselective formation of cyclopentenone B. Stereoselective reduction of B proved to be challenging. Thus, installation of a mesylate group followed by desilylation was crucial to access ketone C with the correct configuration at C6 and C7. Carbonylative esterification afforded ester D, which was further elaborated into amide E. Finally, Dieckmann condensation followed by hemiacetalization furnished (+)-fusarisetin A along with the separable diastereoisomer F (dr = 3:2).

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