DESIGN, SYNTHESIS AND BIOLOGICAL EVALUATION OF MEDICINALLY RELEVANT HETEROCYCLES

Abstract

New methodologies for the synthesis of nitrogenous heterocyclic compounds, namely Isoindolin-1-ones have been reported. The methodologies involve the base-mediated iodoaminocyclization of 2-(1-alkynyl)benzamides. The first methodology involves n-BuLi as an efficient base and leads to the N-cyclization of o-alkynylbenzamides. Interestingly, the second methodology involving the Phosphazene superbase P4-t-Bu works under milder reaction conditions, and quickly affords diverse isoindolin-1-ones in good to excellent yields, in a regio- and stereoselective manner. The reactions are easy to perform, accommodate a variety of sensitive functional groups (including TMS, halogens, etc.), work with other halogen electrophiles (such as ICl, Br2, NBS, etc.), and are also scalable. An interesting reaction mechanism involving the intimate ion pair has been proposed in order to explain the exclusive formation of Z-geometric isomers. The methodology involving the superbase has also been extended for the synthesis of Aristolactams, an important class of natural products. The synthesized isoindolinones have also been evaluated (virtual screening) for their potential biological activities against important cancer drug targets.