Concise synthesis of tetrahydro derivatives of the pyrido[2,3-b]acridine and pyrido[3,2-b]acridine ring systems

5,6,7,8-Tetrahydro-1,4-acridinequinones were readily prepared by Friedlande r reaction between cyclohexanone and 2-amino-3,6-dimethoxybenzaldehydes or 2-amino-3,6-dimethoxyacetophenones; followed by oxidative demethylation. Th eir Diels-Alder reactions with 1-dimethylamino-1-azadienes gave pyrido[3,2- b]acridines in a regioselective fashion. The regiochemistry of the cycloadd ition could be inverted through the introduction of a bromine atom at the C -5 position, to give pyrido[2,3-b]acridines. The latter ring system is a st ructural fragment common to several polyciclic marine natural products with antitumour properties, including ascididemin, eilatin and biemnadin. (C) 1 999 Elsevier Science Ltd. All rights reserved.