Total syntheses of the Strychnos indole alkaloids (-)-tubifoline, (-)-tubifolidine, and (-)-19,20-dihydroakuammicine

Article abstract of DOI:10.1016/S0957-4166(97)00071-2

Two different strategies for the synthesis of pentacyclic Strychnos alkaloids in enantiomerically pure form are explored. Both of them involve the use of enantiopure 2-(4-piperidylmethyl)indoles prepared by kinetic resolution of 1-(3-pyridyl)ethanol, followed by partial reduction of the pyridine ring to the tetrahydropyridine level, Claisen rearrangement of the resulting allylic alcohol, and finally Smith indolization. Whereas 2-(4-piperidylmethyl)indole 6 could not be converted to tetracyclic ABDE substructures of Strychnas alkaloids, photocyclization of chloroacetamide 14, derived from (piperidylmethyl)indole 13, satisfactorily afforded the stemmadenine-type tetracycle 15, which was then converted to the alkaloids (-)-tubifoline, (-)-tubifolidine, and (-19,20-dihydroakuammicine.