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.

Quararibea Metabolites. 4.(1) Total Synthesis and Conformational Studies of (+/-)-Funebrine and (+/-)-Funebral.

Syntheses of racemic forms of the main secondary metabolites of Quararibea funebris, (+/-)-funebrine, (+/-)-funebral, and their biogenetic precursor (+/-)-(2S,3S,4R)-gamma-hydroxyalloisoluecine lactone have been developed. In synthetic studies, a new variation of the Paal-Knorr condensation employing titanium isopropoxide was utilized to construct the pyrrole lactone moiety. Two efficient synthetic approaches to the key (+/-)-gamma-amino lactone have been developed, one based on Claisen chemistry and the other on addition reactions to the butenolide ring of beta-angelicalactone. The restricted rotation around the C(sp(3))-N(sp(2)) bond in the pyrrole lactone structures of (+/-)-funebrine, (+/-)-funebral, and related aldehydes has been probed by conformational dynamic studies, and the barriers for interconversion between conformations have been measured by full NMR line-shape analysis. Molecular mechanics (MMX) and a (1)H-(1)H NOE study indicate a distinct preferred conformation for (+/-)-funebrine.