A synthetic approach to the indole alkaloid apparicine. Synthesis of the ring skeleton

Abstract

1,4,5,7-Tetrahydro-2,5-ethano-2H-azocino[4,3-b]indol-6(3H)-one (2), a compound having the ring skeleton of apparicine (1), has been synthesised via a Mannich type cyclisation of an indol-2-yl piperidin-4-yl ketone acetal. Attempts to extrapolate the approach for the synthesis of the alkaloid itself were frustrated by competing cyclisations leading to 3-(indol-2-yl)-3a,6-methanoperhydrofuro[3,4-c]pyridine and 1,2,3,4,4a,5,7,12,13,13a-decahydropyrido[4′,3′ : 6,7]oxocino[4,3-b]indole systems, as in (30) and (29). A route to α-pyridoylindoles, involving α-acylation of 4,5,6,7-tetrahydro- or 4,7-dihydro-indole and then dehydrogenation, is described.