TOTAL SYNTHESES OF THE STRYCHNOS INDOLE ALKALOIDS (-)-TUBIFOLINE, (-)-TUBIFOLIDINE, AND (-)-19,20-DIHYDROAKUAMMICINE

Two different strategies for the synthesis of pentacyclic Strychnos al kaloids in enantiomerically pure form are explored. Both of them invol ve the use of enantiopure 2-(4-piperidylmethyl)indoles prepared by kin etic resolution of 1-(3-pyridyl)ethanol, followed by partial reduction of the pyridine ring to the tetrahydropyridine level, Claisen rearran gement of the resulting allylic alcohol, and finally Smith indolizatio n. Whereas 2-(4-piperidylmethyl)indole 6 could not be converted to tet racyclic ABDE substructures of Strychnos alkaloids, photocyclization o f chloroacetamide 14, derived from (piperidylmethyl)indole 13, satisfa ctorily afforded the stemmadenine-type tetracycle 15, which was then c onverted to the alkaloids (-)-tubifoline, (-)-tubifolidine, and (-)-19 ,20-dihydroakuammicine. (C) 1997 Elsevier Science Ltd.