Synthesis of δ-lycorane derived from the alkaloid caranine

Abstract

δ-Lycorane (IV), one of the four possible stereoisomers of the skeleton of the Amaryllidaceae alkaloids including lycorine and caranine, was synthesised from methyl 1,2,t-4a,t-9a-tetrahydro-6,7-methylenedioxy-9-oxofluorene-r-1-carboxylate (V). Treatment of its hydrogenation product with base gave the epimeric methyl 1,2,3,4,c-4a,c-9a-hexahydro-6,7-methylenedioxy-9-oxofluorene-r-carboxylate (VII), from which 1,2,3,4,c-4a,c-9a-hexahydro-r-1-hydroxymethyl-6,7-methylenedioxyfluoren-9-one (IX) was prepared. The Schmidt reaction with the fluorenone afforded 1,2,3,4,c-4a,5,6,c-10b-octahydro-r-4-hydroxymethyl-8,9-methylenedioxyphen-anthiridin-6-one (X), which was converted into 1,2,3,4,c-4a,5,6,c-10b-octahydro-8,9-methylenedioxy-6-oxophenanthiridin-r-4-ylacetonitrile (XIII). Hydrolysis of the nitrile followed by cyclisation gave 2,3,r-3a,t-11c-tetrahydro-9,10-methylenedioxy-7H-pyrrolo[3,2,1-de]phenanthiridine-5(4H),7(t-11bH)-dione (XV), furnishing δ-lycorane on reduction with lithium aluminium hydride.