Total synthesis of basiliskamide A

Darren Lipomi
Northern Arizona University

Isolated in 2002 by R. J. Andersen and coworkers, the natural polyketide basiliskamide A showed comparable in vitro activity against Candida albicans to amphotericin B with minimal cytotoxicity.* Our synthetic plan features two successive crotylmetal additions to establish the stereogenic centers of the polypropionate fragment. A chelate-controlled (R,E)-crotylsilane addition provides the C7 and C8 anti relationship, while a (S,S)-diisopropyltartrate-modified (Z)-crotylboronate addition completes the polypropionate portion of the target. The low natural abundance and uncertain absolute stereochemical configuration provide the impetus for this project¾there are no previous syntheses reported. Takai iodoolefination and a palladium-mediated cross-coupling reaction will give the (Z,E)-unsaturated amide side chain and finish the assembly of the natural product. Ideally, this synthesis will also provide an effective route to acquire sufficient material for thorough biological evaluation.