AlCl3-NaI assisted cleavage of polymer-bound esters with concomitant amine coupling and azido-reductive cyclization: synthesis of pyrrolobenzodiazepine derivatives

A practical one-pot solid-phase parallel diversity-oriented synthesis (DOS) strategy has been successfully applied for the construction of scaffolds embedded with privileged pyrrolo [2,1-c][1,4]benzodiazepines (PBDs) and their dilactams. The synthetic approach involves AlCl3-NaI assisted cleavage of resin-bound ester, with amine coupling and tandem azido-reductive cyclization as the key step. The maximum skeletal diversity has been expanded through the introduction of different linkers at A-C8-position of PBD with various substituents from a single key intermediate. Gratifyingly, the final compounds have been purified by the solid-supported liquid-liquid extraction (SLE) technique. Interestingly, some of these molecules have shown enhanced DNA-binding affinity in comparison with naturally occurring DC-81. This novel approach is acquiescent for the construction of new pharmaceutical drug candidates for the evaluation of biological profile in drug discovery. (C) 2013 Elsevier Ltd. All rights reserved.