First biocatalytic synthesis of piperidine derivatives via an immobilized lipase-catalyzed multicomponent reaction

Abstract

Herein, we have developed a reusable catalyst via immobilization of Candida antarctica lipase B (CALB) onto magnetic halloysite nanotubes (MHNTs) for the first biocatalytic synthesis of clinically valuable piperidines in very good yields via a multicomponent reaction of benzaldehyde, aniline and acetoacetate ester. Additionally, the generality of this protocol was explored by catalyzing the reaction of differently substituted aromatic benzaldehydes, anilines and acetoacetate esters. Further, the synthetic utility and reusability of the immobilized biocatalyst were proved by setting up a gram scale reaction which provided the corresponding product in 91% yield, and the catalyst was reusable for up to ten consecutive catalytic cycles. Next, enzyme kinetics studies were performed using immobilized CALB and CALB in pure form. The results (e.g. catalytic efficiency of pure CALB = 21.9 mM s⁻¹ and catalytic efficiency of CALB@MHNTs = 23.8 mM s⁻¹) showed that the immobilized lipase was catalytically more efficient than the pure lipase.