Recent developments in dynamic kinetic resolution

Chemoenzymatic dynamic kinetic resolution (DKR) constitutes a convenient and efficient method to access enantiomerically pure alcohol and amine derivatives. This Perspective highlights the work carried out within this field during the past two decades and pinpoints important avenues for future research. First, the Perspective will summarize the more developed area of alcohol DKR, by delineating the way from the earliest proof-of-concept protocols to the current state-of-the-art systems that allows for the highly efficient and selective preparation of a wide range of enantiomerically pure alcohol derivatives. Thereafter, the Perspective will focus on the more challenging DKR of amines, by presenting the currently available homogeneous and heterogeneous methods and their respective limitations. In these two parts, significant attention will be dedicated to the design of efficient racemization methods as an important means of developing milder DKR protocols. In the final part of the Perspective, a brief overview of the research that has been devoted toward improving enzymes as biocatalysts is presented.

http://pubs.acs.org/doi/pdf/10.1021/jacs.5b01031

Chemoenzymatic dynamic kinetic resolution: a powerful tool for the preparation of enantiomerically pure alcohols and amines.

During the last three decades the use of hydrolases for the catalysis of environmentally friendly organic processes under mild reaction conditions has been well documented. Hydrolases have shown themselves to be ideal tools for the acceleration of synthetic transformations because of their high stability, catalytic efficiency, commercial availability and broad substrate specificity in a wide spectrum of biocatalyzed processes. In recent years, novel examples have appeared related to non-conventional reactions catalyzed by hydrolytic enzymes. Amongst these, lipases and acylases have gained much attention as promiscuous biocatalysts showing good levels of reactivity in C–C bond formation, C–heteroatom bond formation, oxidative processes, and novel hydrolytic reactions. This critical review covers recent investigation in the field of catalytic promiscuity, and highlights the most surprising and uncommon activities that this class of enzymes shows in organic synthetic transformations (111 references).

Hydrolases: Catalytically promiscuous enzymes for non-conventional reactions in organic synthesis

Transaminases have attracted considerable interest in their use as biocatalysts for the synthesis of compounds containing chiral amine units, which are widespread within the pharmaceutical, agrochemical, and fine chemical industry. Recent developments in enzyme- and process-engineering have expedited their use in asymmetric synthesis; however, industrial applications are still hindered by a number of factors, including equilibrium thermodynamics, product inhibition, and poor substrate tolerance. Detailed and comprehensive approaches to each of these challenges have been reported during the last two decades; the most representative enzyme discovery and screening strategies, protein and equilibrium engineering, and immobilization techniques are reviewed herein. Furthermore, we present a detailed look into the applications of transaminases for the synthesis of a variety of amine-containing compounds and the integration of transaminases into multienzymatic systems that allow access to a variety of highly comp...

Discovery, Engineering, and Synthetic Application of Transaminase Biocatalysts

Chemoenzymatic Dynamic Kinetic Resolution of Alcohols and Amines

Dynamic Kinetic Resolution of a Wide Range of Secondary Alcohols: Cooperation of Dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium and CAL‐B

Highly enantioselective ( E >200) N-acylation of nine racemic primary amines with isopropyl methoxyacetate in the presence of Candida antarctica lipase B (Novozym 435) has been reported to yield the unreacted ( S )-amines (ee ⩾98%) and produced the ( R )-amides (ee ⩾95%) at 50% conversion under solvent-free conditions. One of the amines and the acyl donor have been used in an equimolar ratio at room temperature (23 °C). Under the reaction conditions, the reuse stability of Novozym 435 with 1-phenylethylamine (as a model compound) has been shown to be poor while somewhat improved stability has been observed with an in-house prepared sol–gel CAL-B catalyst.

Solvent-free kinetic resolution of primary amines catalyzed by Candida antarctica lipase B: effect of immobilization and recycling stability

Dicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium as Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols

Reusable ω-transaminase sol–gel catalyst for the preparation of amine enantiomers

This paper concentrates on studies of the acylation of alcohols with 3,3-difluoro-4-phenylazetidin-2-one rac - 1 , trans -3-fluoro-4-phenylazetidin-2-one rac - 2 and 4-phenylazetidin-2-one rac - 3 in the presence of immobilized lipase PS from Burkholderia cepacia in dry tert -butyl methyl ether (TBME). Fluorine activation in the compounds studied was essential in order to split the β-lactam ring with lipase PS. The highly enantioselective ring opening of rac - 1 and rac - 2 with methanol (1-butanol was also studied) allowed the preparation of the ( R /(3 R ,4 R ))-β-lactams as the unreacted enantiomers and ( S /(2 S ,3 S ))-β-amino esters as the product enantiomers with an ee >99%. Under the same conditions, rac - 3 was totally unreactive. The possibility for a competing hydrolysis caused by water in the enzyme preparations is also discussed.

Mari Päiviö

Papers

Dynamic Kinetic Resolution of a Wide Range of Secondary Alcohols: Cooperation of Dicarbonylchlorido(pentabenzylcyclopentadienyl)ruthenium and CAL‐B

Solvent-free kinetic resolution of primary amines catalyzed by Candida antarctica lipase B: effect of immobilization and recycling stability

Dicarbonylchloro(pentabenzylcyclopentadienyl)ruthenium as Racemization Catalyst in the Dynamic Kinetic Resolution of Secondary Alcohols

Reusable ω-transaminase sol–gel catalyst for the preparation of amine enantiomers

Enantioselective acylation of alcohols with fluorinated β-phenyl-β-lactams in the presence of Burkholderia cepacia lipase