Recent applications of multicomponent reactions in medicinal chemistry

Palladium Catalyzed Asymmetric Three-Component Coupling of Boronic Esters, Indoles, and Allylic Acetates

“…Enantioselective variants are even more valuable, especially when multiple stereocenters are generated. 1,2 Within the field of multicomponent couplings, boron reagents have proven particularly useful, possibly because the open coordination site on boron can favor pre-assembly of reactants. Examples include 1) enantioselective addition of vinyl boronic esters to imines formed in situ (Petasis-type reaction), 3 2) di-allylation with diboranes to effect conjunctive coupling of multiple aldehydes, 4 and 3) iterative homologation using optically active boronic esters.…”

Modication of Heterocyclic Amino Acids: Histidine and Tryptophan

“…A concept that has been used to rapidly generate molecular diversity is that of multicomponent reactions [148][149][150][151], in which condensation/addition products are generated from three or more starting materials in a single reaction. Carboxylic acids are often found as components in such reactions.…”

Organocatalytic clean synthesis of densely functionalized 4H-pyrans by bifunctional tetraethylammonium 2-(carbamoyl)benzoate using ball milling technique under mild conditions

“…Such diverse biological features have made 4H-pyran derivatives important for further exploration in modern medicinal and combinatorial chemistry (46,47). For instance, 2-amino-4H-chromene derivatives, such as compounds 1 and 2, have been known as anticancer therapeutic agents.…”

“…Table 2. Three-component synthesis of different 2-amino-5,10-dihydro-5,10-dioxo-4H-benzo[g]chromene-3-carbonitrile derivatives (9a-j) via condensation of 2-hydroxynaphthalene-1,4-dione (6), various aldehydes 7a-j and malononitrile (8) in the presence of TEACB (5) hand, compound 3 serves as a precursor for the blood anticoagulant warfarin while compound 4 shows an antibacterial activity ( Figure 1) (46,47).…”