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

Abdulkareem Hamid (1, 2) , Abdelaziz Souizi (3) , Ata Martin Lawson (1, 2) , Mohamed Othman (1, 2) , Alina Ghinet (4, 5, 6) , Benoît Rigo (4, 6) , Adam Daïch (1, 2)

1 URCOM - Unité de Recherche en Chimie Organique et Macromoléculaire
2 INC3M - Institut Normand de Chimie Moléculaire Médicinale et Macromoléculaire
3 UIT - Université Ibn Tofaïl
4 LIRIC - Lille Inflammation Research International Center - U 995
5 Alexandru Ioan Cuza University of Iași [Romania]
6 HEI - Hautes Etudes d’Ingénieur [Lille]

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: Alkaloids analogues; Lewis and Brønsted acids catalysis; π-Cationic cyclization; N-Acyliminium species; Regiospecific imide reduction

Domains: Chemical Sciences

Abdulkareem Hamid, Abdelaziz Souizi, Ata Martin Lawson, Mohamed Othman, Alina Ghinet, et al.. 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. Arabian Journal of Chemistry, 2019, 12 (5), pp.680-693. ⟨10.1016/j.arabjc.2018.03.009⟩. ⟨hal-02413296⟩