Enantiospecific Synthesis of (+)-Alstonisine via a Stereospecific Osmylation Process

The first enantiospecific total synthesis of (+)-alstonisine has been accomplished from D-tryptophan methyl ester 13 in 12% overall yield (in 17 reaction vessels). A diastereospecific osmylation process has been employed as a key step to convert indole 18 into spirocyclic oxindole 19. Mechanistic studies of the stereoselective osmylation of the 2,3-indole double bond of indole alkaloids has been carried out. Compelling evidence for the intramolecular delivery of OsO4 via N b-complexation was obtained for the osmylation process. The correct structure of (+)-alstonisine (1) was determined by NOE spectroscopic experiments and further confirmed by single-crystal X-ray analysis.