Three-component synthesis of disubstituted 2H-pyrrol-2-ones: preparation of the violacein scaffold

An efficient, three-component, microwave-mediated cyclization to prepare the 3,5-disubstituted 2H-pyrrol-2-one core of the bis-indole alkaloid, violacein, is described. Preliminary results indicate an iterative, thermally driven, condensation of a gamma-ketoester, ammonium acetate, and isatin in polyethylene glycol. This methodology is an effective and environmentally benign route to prepare a series of violacein analogs in good overall yields. (C) 2014 Elsevier Ltd. All rights reserved.