Synthesis of 1,2,3,4-tetrahydroascididemin

1,2,3,4-Tetrahydroascididemin was synthesized in six steps from 2-nitro-3,6-dimethoxyacetophenone. The core linear tetracyclic pyrido[2,3-b]acridine system (6) was prepared through combination of a Friedlander reaction and an hetero Diels-Alder cycloaddition as the key steps, and the fifth ring was created using a tandem Mannich reaction-intramolecular imine formation. 1,2,3,4-Tetrahydroascididemin showed excellent in vitro antitumour activity, which was particularly selective for the human non-small cell lung cancer cell line (A-549). (C) 1999 Elsevier Science Ltd. All rights reserved.