Intramolecular N-aza-amidoalkylation in association with Witkop–Winterfeldt oxidation as the key step to synthesize Luotonin-A analogues

An expedient four-step approach for the synthesis of a short library of original analogues of the Topo-I Luotonin-A inhibitor, substituted at their C8- and N15-positions, was investigated. This consists of Rutaecarpines formation, their Witkop–Winterfeldt oxidation followed ultimately with functional adjustment of the pyrroloquinolone intermediates. In the first step of these investigations, Rutaecarpines including the Topo-I poison Evodiamine were obtained via the new tandem N-acylation/aza-amidoalkylation using a nitrogen atom as an internal nucleophile with or without association with a decarboxylation.