Synthetic access to syn-functionalised chiral hydroxy pyrrolidines and pyrrolidones: Evaluation of Alpha-glucosidase inhibition activity, docking studies and pharmacokinetics prediction

Abstract

A new series of syn-functionalised chiral hydroxy pyrrolidines and pyrrolidones containing Alpha,Beta-contiguous stereocenters were synthesized via a diphenylprolinol-catalysed asymmetric cross aldol reaction. The synthesized compounds were characterised and evaluated for their Alpha-glucosidase inhibitory potential. The hydroxy pyrrolidine series (9a-9i) was found to be selectively more potent against the Alpha-glucosidase enzyme as compared to the pyrrolidone series (10a-10i). Pyrrolidine 9b was the most efficacious analogue with an IC sub(50) of 48.31 Mu M. Compounds 9c, 9d, & 9f were also found to be more potent than the standard drugs acarbose, miglitol and deoxynojirimycin. Furthermore, these compounds were investigated by computational studies using the GLIDE docking module of the Schrodinger suite 2021-4 in which 9b and 9c showed more promising results than the standard drugs acarbose, miglitol, and deoxynojirimycin.