Total Synthesis and Biological Evaluation of (−)Apicularen A and Analogues Thereof
- 11 December 2003
- journal article
- research article
- Published by Wiley in Chemistry – A European Journal
- Vol. 9 (24) , 6177-6191
- https://doi.org/10.1002/chem.200305230
Abstract
Apicularen A (1) and related benzolactone acylenamines belong to a growing class of novel natural products possessing highly cytotoxic properties. The challenging structure of 1 includes a 10-membered macrolactone ring, a tetrahydropyran system, an o,m-substituted phenol and a doubly unsaturated acyl group attached on the side chain enamine functionality. The total synthesis of apicularen A described herein involves a strategy equivalent to its proposed biosynthesis and entails a reiterative two-step procedure featuring allylation and ozonolytic cleavage to grow the molecule's chain by one acetate unit at a time. The developed synthetic technology was applied to the construction of a series of apicularen A analogues whose biological evaluation established a set of structure–activity relationships in this new area of potential importance in cancer chemotherapy.Keywords
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