Multicomponent reactions (MCRs) yielding medicinally relevant rings: a recent update and chemical space analysis of the scaffolds

Abstract

In this review we have compiled multicomponent reactions (MCRs) that produce cyclic structures. We have covered articles reported since 2019 to showcase the recent advances in this area. In contrast to other available reviews on this topic, we focus specifically on MCRs with strong prospects in medicinal chemistry. Consequently, the reactions operating in a single-pot and yielding novel rings or new substitution patterns under mild conditions are highlighted. Moreover, MCRs that do not require special reagents or catalysts and yield diverse products from commercially available building blocks are reviewed. The synthetic schemes, substrate scope, and other key aspects such as regio- and stereoselectivity are discussed for each MCR. Using cheminformatic tools, we have also attempted to characterize the chemical space of the scaffolds obtained from these MCRs. We show that the MCR scaffolds are novel, more complex, and globular in shape compared to the approved drugs and clinical candidates. Thus, our review represents a step towards identifying and characterizing the novel ring space that can be accessed efficiently through MCRs in a short timeframe.