Total synthesis and structural elucidation of khafrefungin

Total synthesis and structural elucidation of khafrefungin, a novel antifun gal agent isolated from the fermentation culture MF6020, have been achieved . Unlike other inhibitors that inhibit the corresponding enzyme in fungi an d mammals to the same extent, khafrefungin does not impair sphingolipid syn thesis of mammals. The basic strategy for the structural elucidation is to prepare all stereoisomers of the structurally simplified khafrefungin mimic s 1 and 2 that were designed for the elucidation of C10,11,12 and C2',3',4' relative stereochemistry, respectively. The comparison of their spectra wi th those of natural khafrefungin would result in the identification of eigh t possible stereoisomers, and the analytical details of these eight stereoi somers have led to the complete stereochemical assignment. On the basis of the structural elucidation, the total synthesis of khafrefungin has been ac complished by using tin(II)-catalyzed asymmetric aldol reactions as key ste ps.