Recent Progress and Developments in Chemoenzymatic and Biocatalytic Dynamic Kinetic Resolution

Abstract

Dynamic kinetic resolution (DKR) is a powerful method to construct complex molecules with one or more stereocenters. In light of their exquisite stereospecificity and stereoselectivity, enzymes are becoming widely used as catalysts in DKR. This review summarizes chemoenzymatic and biocatalytic methodologies for DKR that have been developed in the past decade. Additionally, applications of these methodologies in the preparation of active pharmaceutical ingredients and emerging paradigms, including the combined use of biocatalysis and photocatalysis for DKR, are highlighted.

Expanding the Synthetic Toolbox through Metal–Enzyme Cascade Reactions

“…Until 2015, a few interesting reviews appeared in the literature, 36−38 appearing very recently a new one highlighting the possibility to develop multienzymatic and chemoenzymatic DKRs, also including novel approaches through photocatalytic transformations. 39 Herein, we update this topic with recent advances in the field including examples of DKRs of racemic alcohols and amines where the metal catalyzes the racemization of the unreacted enantiomers. Especial attention will be devoted to the most recent strategies focused on the development of DKRs under flow conditions, while in Section 3.2, the potential of bionanohybrids formed by coimmobilization of a lipase and a metal species will be considered to give additional insights in the development of chemoenzymatic DKR processes.…”

“… , The easiest way to carry out these asymmetric transformations involves the use of lipases in organic and neoteric solvents, thus favoring the solubilization of the metal catalyst. Until 2015, a few interesting reviews appeared in the literature, − appearing very recently a new one highlighting the possibility to develop multienzymatic and chemoenzymatic DKRs, also including novel approaches through photocatalytic transformations …”

Preparation of Coupling Catalyst HamZIF-90@Pd@CALB with Tunable Hollow Structure for Efficient Dynamic Kinetic Resolution of 1-Phenylethylamine

“…Metal nanoparticles (MNPs) are the major racemic catalysts, which are prone to migration and agglomeration due to their own high surface energy [ 7 ]. To overcome this limitation, researchers have prepared loaded catalysts with well-dispersed and small metal particle sizes by using carriers [ 8 , 9 ]. Moreover, the enzyme has a considerable performance enhancement by immobilization.…”

Ketoreductase Catalyzed (Dynamic) Kinetic Resolution for Biomanufacturing of Chiral Chemicals

“…For instance, several blockbuster drugs, such as atorvastatin, montelukast, and crizotinib, could be synthesized by the KREDs catalyzed process in the pharmaceutical industry ( Bornscheuer et al, 2012 ; Devine et al, 2018 ; Campos et al, 2019 ). In comparison with the well-known reduction of prochiral ketones to chiral alcohols with one chiral center, (dynamic) kinetic resolution of racemates by KREDs to produce chiral compounds with at least two chiral centers is also an attractive approach in asymmetric synthesis ( Stewart, 2001 ; Kalaitzakis and Smonou, 2013 ; Applegate and Berkowitz, 2015 ; Yang et al, 2022 ). In this review, we describe the advances in the research area of KREDs catalyzed asymmetric synthesis of chiral compounds with at least two stereocenters through KR and DKR approaches.…”