Bisannulation of 2,3-dichloro-1,4-naphthoquinone with o-nitrophenylacetic acid derivatives: A succinct synthesis of the ABCD ring system of alpkinidine

Abstract

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. An annulation strategy involving successive Michael and amino-Michael substitution reactions of 2,3-dichloro-1,4-naphthoquinone has been used to rapidly construct the ABCD ring system of the pyrroloacridine natural product alpkinidine. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.