THE FIRST TOTAL SYNTHESIS OF (-BULLATACIN, A POTENT ANITITUMOR ANNONACEOUS ACETOGENIN, AND (+)-(15,24)-BISEPI-BULLATACIN())

This paper reports the first total synthesis of the natural product ()-bullatacin (1), a representative of potent antitumor Annonaceous ace togenins, as well as a stereoisomer (+)-(15,24)-bisepi-bullatacin (2). In this synthesis, a new, efficient method has been developed to intr oduce the gamma-lactone into the bistetrahydrofuran skeleton through i n situ alkylation of epoxide 4 by the alpha-sulfonyl carbanion of phen yl sulfone 5. The methylated gamma-lactone was successfully synthesize d by a sequence of reactions comprising an aldol reaction, an acidic l actonization, and elimination under mild, basic condition.