De novo asymmetric synthesis of aspergillide A-C

ORGN 677

Yalan Xing,, C. Eugene Bennett Department of Chemistry, West Virginia University, 217 Clark Hall, Prospective St., Morgantown, WV 26505 and George A. O'Doherty,, C. Eugene Bennett Department of Chemistry, West Virgnia University, 284 Prospect Street, 217 Clark Hall, Morgantown, WV 26506.
Aspergillide A-C are cytotoxic 14-membered macrolides isolated from the marine-derived fungus Aspergillus ostianus. An approach to the enantioselective synthesis of aspergillide A-C will be presented. The route features two highly enantioselective Noyori reduction of an ynone and acylfuran to establish the absolute stereochemistry of the molecule. An Achmatowicz reaction followed by a Pd-catalyzed allylation established they pyran ring, where as, and alkyne zipper reaction was used to install the functionality of the remaining macrocycle.