De novo asymmetric synthesis of aspergillide A-C

ORGN 677

Yalan Xing, yxing@mix.wvu.edu, C. Eugene Bennett Department of Chemistry, West Virginia University, 217 Clark Hall, Prospective St., Morgantown, WV 26505 and George A. O'Doherty, george.odoherty@mail.wvu.edu, 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.