Halohydrin Dehalogenases and Their Potential in Industrial Application – A Viewpoint of Enzyme Reaction Engineering

Abstract

At the moment, there are approx. 100 published papers investigating halohydrin dehalogenases from different aspects; enzymology, molecular biology and reactions they can catalyse. Unquestionably, these enzymes are of great importance and hold an immense potential due to the wide spectrum of different compounds that can be synthesized by their action. These compounds, such as chiral epoxides, β‐substituted alcohols, oxazolidinones etc., significantly enrich the chemist's toolbox and, moreover, open the possibility for the synthesis of even more complex compounds. Still, there are many unknowns, and it is the purpose of this work to demonstrate the possibilities and bottlenecks, in scientific sense, that could further help in broadening the applicative potential of these fascinating enzymes.

Enzymatic Kinetic Resolution of Bulky Spiro-Epoxyoxindoles via Halohydrin Dehalogenase-Catalyzed Enantio- and Regioselective Azidolysis

“…Enzymatic transformations are appreciated by many good features such as high selectivity, milder reaction conditions, and biocompatibility, which become an alternative powerful tool in organic synthesis. − Halohydrin dehalogenases (HHDHs) are attractive enzymes with promiscuous catalytic activity, which can catalyze the dehalogenation of vicinal haloalcohols with the formation of epoxides, − as well as the reverse reaction that ring-opening of epoxides with a set of negatively charged nucleophiles such as azide. − HHDHs have been well studied in catalytic kinetic resolution of epoxides via anion nucleophile-mediated ring-opening reactions. − However, kinetic resolution of bulky epoxides such as spiro-epoxyoxindoles catalyzed by HHDH is challenging and has not been explored until now. Herein, we report a biocatalytic kinetic resolution process for enantio- and regioselective ring-opening of spiro-epoxyoxindoles via HHDH-catalyzed azidolysis, affording various chiral spiro-epoxyoxindoles and 3-(azidomethyl)-3-hydroxy­oxindoles in good yields and optical purity (Figure c).…”

Insights into the molecular determinants of thermal stability in halohydrin dehalogenase HheD2

“…Halohydrin dehalogenases (HHDHs, also called haloalcohol dehalogenases or halohydrin hydrogen‐halide‐lyases) belong to the enzyme class of lyases (http://www.chem.qmul.ac.uk/iubmb/enzyme/EC%A04/5/1/.html‐) and catalyse the reversible dehalogenation of vicinal haloalcohols with formation of the corresponding epoxides [1]. In the reverse reaction, epoxide ring opening, a number of small anionic nucleophiles such as cyanide, nitrite, azide, cyanate or thiocyanate are accepted resulting in the irreversible formation of novel C‐C, C‐O, C‐N or C‐S bonds, which makes these enzymes very attractive for biocatalytic applications [2,3]. The most prominent example is probably their use in the synthesis of ethyl ( R )‐4‐cyano‐3‐hydroxybutyrate, a chiral synthon for the production of statin side chains [4].…”

Gram-Scale Domino Synthesis in Batch and Flow Mode of Azetidinium Salts

“…The possibility of easily obtaining from it β-aminoalcohols as key intermediates for β-blockers, like atenolol and propranolol, is one of the most attractive applications of this compound, which today is used also in polymer synthesis to prepare cellulose-based materials. 16 − 18…”

“…In particular, epoxide aminolysis has been extensively studied and various conditions have been developed, including those based on microwave- and ultrasound-assisted methods, on the use of lanthanide or aluminum triflates and Lewis acids reagents, and on solid acid supports. − Among epoxides, epichlorohydrin presents a chlorine atom as a substituent of the epoxy motif and is an essential building block for pharmaceutical and fine chemical synthesis, due to its peculiar reactivity toward nucleophiles. The possibility of easily obtaining from it β-aminoalcohols as key intermediates for β-blockers, like atenolol and propranolol, is one of the most attractive applications of this compound, which today is used also in polymer synthesis to prepare cellulose-based materials. − …”