Recent developments in thiochromene chemistry

Abstract

Thiochromenes are versatile sulfur-containing heterocyclic compounds that have received considerable interest in drug discovery because of their ability to act as crucial building blocks for synthesizing bioactive compounds. In particular, these scaffolds have found utility in the design of anticancer, anti-HIV, antioxidant, and antimicrobial agents, among others. Despite their pharmacological potential, the synthesis of these scaffolds is less explored in contrast to their oxygen-containing counterparts. This review classifies the synthetic processes into Michael addition, cycloaddition, ring-opening, coupling, cyclization and Diels–Alder reactions, and others. Reaction mechanisms, circumstances, and important instances are thoroughly discussed in each area. For instance, chiral catalysts and substrates like mercaptobenzaldehyde and cinnamaldehyde are used in Michael addition processes to achieve excellent enantioselectivity. In cycloaddition reactions, readily available substrates such as thioisatins and alkynes achieve regioselectivity and product production. Thiochromenes are also synthesized by ring-opening reactions with epoxides or aziridines. These reactions demonstrate the importance of catalysts and solvents in reaction control, particularly palladium catalysts for aryl halides and thiol coupling processes. Another major class discussed is cyclization reactions with alkynyl thiols and alkynes under regulated temperature and pressure conditions to efficiently synthesize thiochromenes. With the use of chiral substrates and catalysts, Diels–Alder processes increase yields and selectivity and enhance the variety of thiochromene compounds. This review emphasizes the versatility of thiochromenes in drug discovery and consolidates the existing literature on thiochromenes, scrutinizing the gaps and opportunities for synthesizing novel thiochromene-containing lead molecules.