H₂-Driven biocatalytic hydrogenation in continuous flow using enzyme-modified carbon nanotube columns

Abstract

We describe the implementation of a system of immobilised enzymes for H-driven NADH recycling coupled to a selective biotransformation to enable H-driven biocatalysis in flow. This approach represents a platform that can be optimised for a wide range of hydrogenation steps and is shown here for enantioselective ketone reduction and reductive amination.

Rapid, Heterogeneous Biocatalytic Hydrogenation and Deuteration in a Continuous Flow Reactor

“…We recently described initial results using H 2 -driven biocatalytic systems supported in a simple flow reactor. [26] This combines the advantages of supported enzymes in flow, with H 2 gas for greener cofactor recycling, to overcome some of the key challenges of biocatalysis. This set-up employed hydrogenase/NAD + -reductase as the H 2 -driven cofactor recycling system.…”

Direct Reductive Amination of Carbonyl Compounds with H2 Using Heterogeneous Catalysts in Continuous Flow as an Alternative to N‐Alkylation with Alkyl Halides

“…[3] In the current transformation, a product and even excess starting materials and others are released from a catalyst automatically by flow, assuming that overreactions and other byproducts formation could be suppressed and the functional group-compatibility issue might be solved. In literature, however, examples of carbonyl-DRA with H 2 using heterogeneous catalysts are very limited; Pd/C, [4] supported FeNi, [5] and enzyme [6] were used, Scheme 1. CÀN bond formation through substitution (1) and direct reductive amination of carbonyl compounds (carbonyl-DRA) (2).…”

“…[15] Model substrates such as piperidine and pyrrolidine also afforded excellent yields (compounds 4 and 5), even though not quantitative, certainly because of their intrinsic volatility. Other 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 medicinally privileged substrates like N-ethylpiperazine and morpholine could also be benzylated in almost perfect yields (6,7). In addition, the carbamate moiety survived entirely throughout the process (compound 8).…”

Recent Progress in Continuous‐Flow Hydrogenation

“…This merit makes enzymes a good candidate for flow chemistry. A recent example of enzyme‐catalyzed enantioselective hydrogenation of ketones was reported by Vincent and co‐workers . In the reported reaction, enzymes could not directly use the hydrogen molecule, and thus instead the hydride transfer needs to be assisted by cofactors such as NAD + (NAD=nicotinamide adenine dinucleotide).…”