apicularen-a and Ovarian-Neoplasms

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.

Topics: Amines; Antineoplastic Agents; Benzene Derivatives; Bridged Bicyclo Compounds, Heterocyclic; Cell Line, Tumor; Female; Humans; Lactones; Macrolides; Models, Chemical; Models, Molecular; Ovarian Neoplasms; Phenols; Pyrans; Structure-Activity Relationship