Total synthesis of the sphingolipid biosynthesis inhibitor, fumonisin B1

ORGN 786

Claney L. Pereira,, Yi-Hung Chen,, and Frank E. McDonald, Department of Chemistry, Emory University, 1515, Dickey Drive, Atlanta, GA 30322
Fumonisin B1(1) is a primary mycotoxin produced by the fungus Fusarium verticillioides. Due to its biological role as a sphingolipid biosynthesis inhibitor and structural similarity with sphingoid bases, we have accomplished its total synthesis. Our convergent approach utilizes new methodology based on oxonia-Cope rearrangements to stereoselectively synthesize the key coupling intermediates A and B. An efficient synthesis of the tricarballylic acid synthon C is another highlight of this approach. The synthetic design also enabled us to synthesize the hydrolyzed form of fumonisin B1, which also provides a starting point for exploring the structure-activity relationships of fumonisin analogs as anticancer agents.