Bisannulation of 2,3-Dichloro-1,4-naphthoquinone with o-Nitrophenylacetic Acid Derivatives: A Succinct Synthesis of the ABCD Ring System of Alpkinidine

Three bisannulation strategies have been used to rapidly construct pentacyclic benzo-fused pyrrolo[4,3,2-mn]acridines, similar to several biologically active natural products. The key steps involve Michael substitution of 2,3-dichloro-1,4-naphthoquinone with o-nitrophenylacetic acid derivatives, followed by domino amino-Michael substitutions/cyclisations. The most efficient of these syntheses provided a model compound (1) including the ABCD ring-system of alpkinidine, in just three steps and 55% overall yield.