Synthesis of Pyridine and Quinoline Based Novel Nheteroaromatics and Targeting Activity Against Macrophage-associated Disease

Abstract

The work embodied in this thesis describes the synthesis of pyridine and quinoline based novel N-heteroaromatics and targeting activity against macrophageassociated disease. The work covers mainly four areas, (i) Development of novel methodology for the one pot synthesis of linear and angular fused quinazolinones. (ii) Synthesis of tetrahydropyrrolo[3',4':3,4] pyrrolo[2,1-a] isoquinoline-9,11-dione derivatives via a simple and convenient multi compartment reaction in aqueous miceller system. (iii) One pot synthesis of symmetrically 1, 4-disubstituted piperazine- 2, 5-diones. (iv) and Bioactivity of the above synthesized compounds as antileishmaniasis againsts ( Macrophage associated disease). The Chapter I begins with a review on strategic development toward the Pyridine and quinoline based Synthetic and Natural products against Leishmaniasis. Chapter II deals with the development of one step methodology using amino heterocycles and o-bromo benzyl/naphthyl bromides as reactants to produce Nheteroaromatic cationic intermediates, which upon base catalyzed nucleophilic aromatic substitution followed by in situ aerial oxidation at the benzylic position smoothly furnished the angular and linear quinazolinones . Chapter III presents the development of an efficient and environment-friendly novel approach for the synthesis of tetrahydropyrrolo[3',4':3,4] pyrrolo[2,1-a] isoquinoline-9,11-dione derivatives using isoquinolinium ylide (generated in situ from isoquinoline and phenacyl bromide in presence of a base) and an activated dienophile (aryl maleimide) in micellar solution at ambient temperature. Chapter IV describes a series of diketopiperazine derivatives synthesized by self-condensation of differently substituted α-chlorophenyl acetamides in a one-pot sequence in presence of sodium hydride under nitrogen atmosphere. Chapter V deals with the bio activity of the above synthesized compounds against lishmaniasis. The promising activities of the compounds are investigated further with in vivo study