Total synthesis and biological evaluation of (-)apicularen A and analogues thereof.

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.

• Authors: K C Nicolaou, David W Kim, Rachid Baati, Aurora O'Brate, Paraskevi Giannakakou
• Journal: Chemistry (Weinheim an der Bergstrasse, Germany) (Chemistry) Vol. 9 Issue 24 Pg. 6177-91 (Dec 15 2003) ISSN: 0947-6539 [Print] Germany
• PMID: 14679529 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Amines
• Antineoplastic Agents
• Benzene Derivatives
• Bridged Bicyclo Compounds, Heterocyclic
• Lactones
• Macrolides
• Phenols
• Pyrans
• apicularen A

Topics

• Amines (chemistry)
• Antineoplastic Agents (chemical synthesis, pharmacology)
• Benzene Derivatives (chemistry, metabolism)
• Bridged Bicyclo Compounds, Heterocyclic (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Female
• Humans
• Lactones (chemistry)
• Macrolides (chemistry)
• Models, Chemical
• Models, Molecular
• Ovarian Neoplasms (drug therapy)
• Phenols (chemistry)
• Pyrans (chemistry)
• Structure-Activity Relationship