A chemoenzymatic total synthesis of the phytotoxic undecenolide (?)-cladospolide A

Organic & Biomolecular Chemistry Pub Date: 2004-06-23 DOI: 10.1039/B401829J

Abstract

An eleven-step synthesis of the title compound (1) from biocatalytically-derived and enantiomerically pure ‘building blocks’ alcohol (R)-(?)-9 and ester 13 is described. Attempts to construct the twelve-membered lactone ring of cladospolide A in a direct manner by using a ring-closing metathesis (RCM) reaction failed. However, a ten-membered lactone, 19, could be constructed by such means and this was then subject to a two-carbon homologation sequence involving, inter alia, Wadsworth–Horner–Emmons and Yamaguchi lactonisation reactions in the closing stages of the synthesis. The impact of substituent stereochemistries and protecting groups on the RCM reaction leading to various ten-membered lactones is also described.

Graphical abstract: A chemoenzymatic total synthesis of the phytotoxic undecenolide (?)-cladospolide A
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