Synthesis of Lactone– Derived Aromatic Scaffolds of Synthetic and Therapeutic Importance

Abstract

The second half of last century has witnessed an enormous and iterative progress in organic synthesis. Consequently the advent of inventive concepts with high conventional power and the development of new strategies and technologies led to the evolution of several bicyclic and tricyclic nitrogen based heterocycles. Terrifying goals were achieved in this direction owing to the constant efforts in the search of new reagents and methods for chemically efficient reactions. At present, research in this field is even more actively promoted by the interplay of organic chemistry and various disciplines of science such as biological sciences and material chemistry that are posing a pressing demand for synthetic molecules in meaningful scale with high level of purity. This is the case of heterocyclic compounds whose utility in organic synthesis, although recognized in recent times, is now well established. The publication in 1974 of the Meyers book entitled Heterocycles in Organic Synthesis describing the main transformations of various heterocycles into common functional groups highlighted the concept of heterocycle-functional group equivalence as a powerful tool in new synthetic programs. Reviews and articles dealing with the use of readily available and simple heterocycles were also reported. The thesis is divided into five chapters. Chapter 1. It deals with the review on acridine and their annulated analogs. We have compiled the publications and patents dealing with the synthesis, reactivity, chemical properties, biological properties of acridine and natural products based on acridine and their annulated analogues. Chapter 2. Quinoline, acridine and related N-heterocyclic systems like annulated phenanthridine are key structural motifs found in a large number of biologically important natural alkaloids isolated from plant and marine sources and represent privileged scaffolds in medicinal chemistry. In this chapter we have demonstrated a new protocol for the synthesis of functionalized 5,6-dihydro-4H-benzo[kl]acridines through unprecedented „Bridged Annulation‟ of 2H-pyran-2-ones with 9-methyl-3,4-dihydroacridin-1(2H)-one in high yields, under basic conditions at room temperature. Chapter 3. Over the past two decades, organic fluorophores have received overwhelming scientific and technological attention due to their tremendous potential as bio-imaging agents, chemosensors, fluorescent probes and as electroluminescent materials. In this context we demonstrated a new protocol for the synthesis of functionalized benzo[a]acridines through ring transformation reactions of 2H-pyran-2-ones with 3,4- dihydroacridin-1(2H)-one or 5,7-dibromo-3,4-dihydroacridin-1(2H)-one in high yields. Chapter 4. Synthesis of quinoline derivatives is of considerable interest in the field of organic and pharmaceutical chemistry, since this basic skeleton is widespread in natural products and biologically active substances. In this chapter, we demonstrated a highly convenient synthesis of various functionalized substituted quinoline such as 3- phenylquinoline, 6-(quinolin-3-yl)-2H-pyran-2-one, 3-(naphthalen-1-yl)quinoline, 3- (isoquinolin-8-yl)quinoline, 3-(benzo[7] annulen-1-yl)quinoline through ring transformation strategy. Chapter 5. Every year malaria infection is estimated to affect 216 million people worldwide leading to almost 1 million fatal outcomes. For this purpose new, highly efficacious drugs for the treatment of malaria is urgently needed. In this chapter, we demonstrated a highly convenient synthesis of various hybrid molecules and there antimalarial activity in in vitro and in vivo models.