Amipurimycin: Total Synthesis of the Proposed Structures and Diastereoisomers

The proposed diastereoisomers (1a-d) together with their C8'-epimers (1e-h) of amipurimycin, a unique antifungal peptidyl nucleoside antibiotic, have been synthesized for the first time. The synthetic approach is efficient and stereo-divergent, and features a stereoselective aldol condensation to build the branched C9 sugar amino acid skeleton and a regio- and stereocontrolled gold(I)-catalyzed N-glycosylation to furnish the purine nucleoside. Analysis of the NMR data suggests that the previously assigned configuration of the tertiary C3' in amipurimycin should be of opposite configuration.