Vinyl azides in heterocyclic synthesis. Part 7. Synthetic studies on the cytotoxic marine alkaloid amphimedine

Abstract

In an approach to the synthesis of the pentacyclic alkaloid amphimedine (1), a key tetracyclic structure (6) is readily constructed from 2-methoxyacridine-9-carbaldehyde in three steps. Condensation of the aldehyde (2) with methyl azidoacetate gives the vinyl azide (3) which on thermolysis in xylene gives the pyridoacridines (4) and (5) in high yield (78% and 19% respectively); this represents the first cyclisation of a vinyl nitrene to a peri-position. Oxidation of the major pyridoacridine (4), or of the mixed pyridoacridines (4) and (5), with manganese dioxide gives the pyridoacridone (6), but neither (6) nor the analogous isopropyl ester (9) undergoes Diels–Alder reaction with the azadiene (7).