Multicomponent Reaction-Assisted Drug Discovery: A Time- and Cost-Effective Green Approach Speeding Up Identification and Optimization of Anticancer Drugs

Abstract

Multicomponent reactions (MCRs) have emerged as a powerful strategy in synthetic organic chemistry due to their widespread applications in drug discovery and development. MCRs are flexible transformations in which three or more substrates react to form structurally complex products with high atomic efficiency. They are being increasingly appreciated as a highly exploratory and evolutionary tool by the medicinal chemistry community, opening the door to more sustainable, cost-effective and rapid synthesis of biologically active molecules. In recent years, MCR-based synthetic strategies have found extensive application in the field of drug discovery, and several anticancer drugs have been synthesized through MCRs. In this review, we present an overview of representative and recent literature examples documenting different approaches and applications of MCRs in the development of new anticancer drugs.

Humic Acid: A Promising and Green Bioorganic Catalyst in Organic Syntheses

“…Thus, MCRs are generally the choice of synthetic chemists to avoid multistep chemical reactions. [23][24][25][26][27] The humic acid as an efficient catalyst has been explored in MCRs.…”

Diastereoselective ZnCl2-Mediated Joullié–Ugi Three-Component Reaction for the Preparation of Phosphorylated N-Acylaziridines from 2H-Azirines

“…Among them, the more versatile isocyanide-based MCRs form the backbone of today’s MCRs, such as the Ugi four-component reaction (U-4CR), which comprises the condensation of primary amines, carbonyl compounds, carboxylic acids and isocyanides to furnish dipeptide-like structures [ 9 , 10 , 11 , 12 , 13 ]. As the U-4CR mechanism occurred via the in situ formation of an imine intermediate, the employment of a cyclic imine instead of the amine and the carbonyl components in the Ugi protocol is a simple concept that supplies the robust Joullié–Ugi three-component reaction (JU-3CR).…”

Acid Catalyzed Multicomponent Reaction to Access Functionalized N‐Benzhydryl Amides: A Tandem Ritter Reaction

“…[14][15][16] Multicomponent reactions offer viable solutions for molecular complexity from simple starting materials in one step. [17,18] Thus, multicomponent tandem Ritter reactions can be applied for the construction of complex amides in one step with high atom economy and bond forming efficiency. [11] Although tandem Ritter reactions have been reported during past several years, it is a challenge for synthetic organic chemists to design and develop new and efficient reactions for applications in the synthesis of bioactive compounds.…”

“…entry 17). Prolonged reaction times or reduced reaction temperature (60 °C, RT) proved detrimental (Table1, entries[18][19]. Controlled experiment in the absence of acid catalyst was unsuccessful (…”