Benzo[7,8]indolizinoquinoline scaffolds based on Mg(ClO4)2-promoted regiospecific imide reduction and π-cyclization of N-acyliminium species. Analogues of the topo-1 poison rosettacin and 22-hydroxyacuminatine alkaloids

• Main Authors: Abdulkareem Hamid, Abdelaziz Souizi, Ata Martin Lawson, Mohamed Othman, Alina Ghinet, Benoît Rigo, Adam Daïch
• Format: Article
• Language: English
• Published: Elsevier 2019-07-01
• Series: Arabian Journal of Chemistry
• Online Access: http://www.sciencedirect.com/science/article/pii/S1878535218300674
• ISSN: 1878-5352

A general five-step synthesis of a short library of benzo[7,8]indolizinoquinolinine analogues of the topoisomerase-1 (topo-1) poison rosettacin and 22-hydroxyacuminatine alkaloids from DMAD and ortho-ketoanilines is reported. This consists on successively, the tandem aza-Michael addition/cyclodehydration, the hydrolysis of the resulting diesters into corresponding o-dicarboxylic acids, and the tandem intermolecular amidation/cyclodehydration into N-substituted imides. The regioselective reduction of one imide carbonyl into corresponding α-hydroxy lactams promoted by a Lewis acid Mg(ClO4)2 was followed ultimately with TFA-promoted π-cationic cyclization via stable N-acyliminiums species as an important key step. Keywords: Regiospecific imide reduction, Lewis and Brønsted acids catalysis, N-Acyliminium species, π-Cationic cyclization, Alkaloids analogues