Abstract
Quinazolinones are pharmacophoric scaffolds that can be found in a wide range of biologically active natural products, pharmaceutical medications, synthetic materials, veterinary supplies, and agrochemicals. The quinazolinone core serves as a critical scaffold for compounds with diverse therapeutic and biological activities such as antimicrobial, antimalarial, anticonvulsant, anticancer, antitubercular, anti-inflammatory, antihypertensive, kinase inhibitory activities, and cellular phosphorylation inhibition. Quinazolinone core also serves as a foundation for the structures of over 200 naturally occurring alkaloids identified from a variety of plant groups and microorganisms such as Peganum nigellastrum, and Dichroa febrifuga. Chapter 1: Quinazolinones Synthesis, Reactivity and Biological Activities This chapter provides a brief introduction to isolation and biological significance of quinazolinones natural products. The synthesis of 2-substituted 4(3H)-quinazolinones, 3-substituted 4(3H)-quinazolinones, 2,3-disubstituted 4(3H)-quinazolinones and poly heterocyclic-fused quinazolinones is described. We explain the reactivity of 4(3H)-quinazolinones at the 2-methyl group and the 3-amino group. We also reviewed the chemical reactions of 4(3H)-quinazolinones such as electrophilic substitutions and cycloaddition reactions. Finally, details about the biological activities of quinazolinones are included. Chapter 2: Synthesis of Quinazolinones Utilizing Isatoic Anhydride This section examines the methods described in the literature for synthesizing some of the quinazolinone derivatives from isatoic anhydride. Isatoic anhydrides undergo nucleophilic ring opening with a large number of nitrogen nucleophiles, followed by electrophilic cyclocondensation, in order to produce a range of quinazolinone derivatives commonly employed in medicine and pharmacology. We examine the multicomponent one-pot synthesis to construct alkaloids such as evodiamine and tryptanthrin along with other efforts to access the biologically important quinazolinones. Chapter 3: Synthesis of Complex Quinazolinones Utilizing 2-Substituted 4(3H)-Quinazolinones In this chapter, we delineate the efforts of employing 2-substituted 4(3H)-quinazolinones, which are in turn produced from anthranilamide, as a starting point for the synthesis of tricyclic quinazolinones, and other additional fused quinazolinone natural products. We have primarily investigated methods to employ the ethyl-4-oxy-3H-quinazoline-2-carboxylate and 2-methylquinazolin-4(3H)-one in the total synthesis of a variety of quinazolinones. Chapter 4: Utilizing Deoxyvascinone and Its Homologs in the Synthesis of Complex Quinazolinones Deoxyvascinone is a crucial precursor in the synthesis of some natural alkaloids; we reasoned that we can access more complex alkaloid derivatives using the tricyclic deoxyvascinone and its homologs if we could scale the production of the deoxyvascinone and develop some new chemistry. We reasoned that the chemical functionalizations at the C-3 position of deoxyvascinone will allow us to access more complex natural alkaloids. Thus, the Claisen-Schmidt condensation allowed access to isaindigotone derivatives, and the Vilsmeier-Haack reaction enabled the access to spiro quinazolinones, and the Pictet-Spengler reaction will allow to access peharmaline A derivatives. The central theme of our research has been our quest to access the complex tricyclic quinazolinones and natural alkaloids by relyingon simple starting materials and common reagents via efficient and economical routes that are devoid of toxic and expensive reagents. We also wanted to avoid expensive catalysts, such as transition metal complexes and drastic reaction conditions. Finally, we aimed to develop modular chemistry to extend to the synthesis of the analogues for further exploration of their biomedicinal potential.