TOTAL SYNTHESIS OF INDOLE ALKALOIDS - A NEW STRATEGY FOR (+/-)-19-OXOASPIDOSPERMIDINE AND (+/-)-19-OXOASPIDOFRACTININE

A synthesis for the preparation of 19-oxoaspidospermidine (1) and 19-oxoaspidofractinine (2) has been developed beginning with tetracyclic amido alcohol 9. Dehydration of 9 gave enamide 10. Reduction to the corresponding enamine followed by reaction with acetyl chloride afforded the tetracyclic enamino ketone 12. Studies on the selective reduction of the olefinic bond of the enamino ketone moiety of 12 were carried out. Removal of N-4 protecting group and further alkylation with a three carbon atoms appendage gave compounds 17. Cyclization to pentacyclic product 18 was achieved using NaH in a benzene/THF solution. After deprotection of the N-l atom and oxidation to the unstable indolenine 22, a biomimetic Mannich type cyclization led to 19-oxoaspi-dofractinine (2), a direct precursor of aspidofractinine 6. © 1990, American Chemical Society. All rights reserved.