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Total Synthesis and Biological Evaluation of (−)Apicularen A and Analogues Thereof
Author(s) -
Nicolaou K. C.,
Kim David W.,
Baati Rachid,
O′Brate Aurora,
Giannakakou Paraskevi
Publication year - 2003
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200305230
Subject(s) - tetrahydropyran , total synthesis , chemistry , stereochemistry , cleavage (geology) , enamine , ring (chemistry) , combinatorial chemistry , organic chemistry , biology , paleontology , fracture (geology) , catalysis
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.