Total Synthesis and Biological Evaluation of (-)Apicularen A and Analogues Thereof Academic Article uri icon


MeSH Major

  • Antineoplastic Agents
  • Bridged Bicyclo Compounds, Heterocyclic


  • 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.

publication date

  • December 15, 2003



  • Academic Article



  • eng

Digital Object Identifier (DOI)

  • 10.1002/chem.200305230

PubMed ID

  • 14679529

Additional Document Info

start page

  • 6177

end page

  • 91


  • 9


  • 24