Synthesis of Enantiopure Drugs and Drug Intermediates UsingIn SilicoGenerated Archetype Biocatalyst: A Case Study Using Alprenolol as a Model Drug

Abstract

Biocatalytic approach aided by in silico screening methods may become dominant for the synthesis of drugs and drug intermediates in enantiopure forms over the other organo-chemical methods. Here we investigated a suitable biocatalyst for the kinetic resolution of a racemic drug intermediate using enzyme-ligand based in silico studies using alprenolol as a model drug. With the aid of docking studies, we have demonstrated the effect of H-bond length between the interacting atoms of ligand and the residue at the active site of the enzyme, on the rate and selectivity of the transesterification reaction. The foundation of the study is the screening of several biocatalysts (in this case, lipases) using docking calculations and finding out significantly active biocatalyst. Among the various lipases examined via computational as well as wet lab screening, Candida rugosa lipase (CRL 62316) proved to be the most efficient one to catalyze the resolution of (RS)-1-(2-allylphenoxy)-3-chloropropan-2-ol to (R) enantiomer with highest conversion, enantiomeric excess and enantiomeric ratio. This study signifies the importance of combining docking studies with wet laboratory techniques.