Synthesis and Antiproliferative Activity of Polysubstituted Tetrahydropyridine and Piperidin-4-one-3-carboxylate Derivatives

A highly atom‐economic one‐pot multicomponent synthesis of polysubstituted tetrahydropyridines (THPs) is described. The reaction of anilines, aromatic aldehydes, and β‐keto esters proceeds in the presence of catalytic amount of zirconium tetrachloride, and the products can be further converted to the corresponding piperidin‐4‐one‐3‐carboxylates under acidic conditions. The two sets of products were evaluated for their anticancer activity and some of these compounds, particularly the piperidin‐4‐one‐3‐carboxylates have significant anticancer activity. All in one: A one‐pot multicomponent synthesis of highly substituted tetrahydropyridines (THPs) catalyzed by zirconium tetrachloride is described. The THPs can also undergo a further facile conversion under acidic conditions to give piperidin‐4‐one‐3‐carboxylates. An antiproliferative assay with the obtained THPs and piperidin‐4‐one‐3‐carboxylates in four human cancer cell lines revealed that most of the compounds possess good in vitro anticancer activity.