Total synthesis of O-methylsterigmatocystin using N-alkylnitrilium salts and carbonyl-alkene interconversion in a new xanthone synthesis

A general strategy is described for the preparation of substituted xanthone s and embodied in the preparation of (+/-)-O-methylsterigmatocystin (OMST), the most advanced, known intermediate in the biosynthesis of aflatoxin. Th e essential features of this approach are the reaction of N-alkylnitrilium salts with activated aromatic rings, and protection of the derived xanthone s as their corresponding alkenyl xanthenes. The latter are readily synthesi zed by reaction with n-butyllithium and dehydration. The resulting stabiliz ation of the xanthone nucleus enables a wide range of chemical modification reactions to be carried out, and a facile and unusual cleavage of the alke ne with peracid restores the desired xanthone. Compatibility of these opera tions with the preparation of the sensitive dihydrobisfuran is exemplified in the synthesis of OMST.