Stereoconvergent Reduction of Activated Alkenes by a Nicotinamide Free Synergistic Photobiocatalytic System

Abstract

There is a growing interest in developing cooperative chemoenzymatic reactions to harness the reactivity of chemical catalysts and the selectivity of enzymes for the synthesis of nonracemic chiral compounds. However, existing chemoenzymatic systems with more than one chemical reaction and one enzymatic reaction working cooperatively are rare. Moreover, the application of oxidoreductases in cooperative chemoenzymatic reactions is limited by the necessity of using expensive and unstable redox equivalents such as nicotinamide cofactors. Here, we report a light-driven cooperative chemoenzymatic system comprised of a photoinduced electron transfer reaction (PET) and a photosensitized energy transfer reaction (PEnT) with an enzymatic reduction in one-pot to synthesize chiral building blocks of bioactive compounds. As a proof of concept, ene-reductase was directly regenerated by PET in the absence of external cofactors. Meanwhile, enzymatic reduction worked cooperatively with photocatalyst-catalyzed energy transfer that continuously replenished the reactive isomer from the less reactive one. The whole system stereoconvergently reduced E/Z mixtures of alkenes to the enantiopure products. Additionally, enantioselective enzymatic reduction worked competitively with photocatalyst-catalyzed racemic background reaction and side reactions to channel the overall electron flow to the single enantiopure product. Such a light-driven cooperative chemoenzymatic system holds great potential for asymmetric synthesis using inexpensive petroleum or biomass-derived alkenes.

Ene‐Reductase: A Multifaceted Biocatalyst in Organic Synthesis

“…The highest conversion was observed with 5 % of Flavin mononucleotide (FMN) or 5 % of the cationic iridium(III) complexes [Ir(dmppy) 2 (dtbbpy)]PF 6 (as photocatalyst), and YersER or XenB (as the source of ene‐reductase) gave the highest yield and enantioselectivity. A recent report in 2020 by the Zhao group introduced a light‐driven cooperative chemoenzymatic system comprised of a photoinduced electron transfer reaction (PET) and a photosensitized energy transfer process (PEnT) with an enzymatic reduction for the stereoselective synthesis of many bioactive compounds [100] . In this system, 1 % cationic iridium complex [Ir(dmppy) 2 (dtbbpy)]PF 6 was used to convert a less reactive isomer to a more reactive one which further underwent reduction by ene‐reductase to form a product with excellent yield.…”

“…A recent report in 2020 by the Zhao group introduced a light-driven cooperative chemoenzymatic system comprised of a photoinduced electron transfer reaction (PET) and a photosensitized energy transfer process (PEnT) with an enzymatic reduction for the stereoselective synthesis of many bioactive compounds. [100] In this system, 1 % cationic iridium complex [Ir(dmppy) 2 (dtbbpy)]PF 6 was used to convert a less reactive isomer to a more reactive one which further underwent reduction by ene-reductase to form a product with excellent yield. Under blue light, FAD regenerates ER-FMNH À by directly transferring electrons from cheap electron donors EDTA to the FMN which helped to continue the catalytic cycle (Scheme 10c).…”

“…(a) Reduction of ketoisophorone to (R)-levodione using CNT/ pgC 3 N 4 film cathode, [97] (b) Conversion of isomeric mixture of 2-phenylbut-2enedioic acid dimethyl ester to stereoselective dimethyl 2-phenylsuccinate molecule under photoenzymatic conditions, [99] (c) Light-driven co-operative chemoenzymatic system comprised of a photoinduced electron transfer reaction (PET) and a photosensitized energy transfer process. [100] Scheme 11. Dehalogenation of α-Bromo-α-aryl ester via a single electron process catalysed by ene-reductases.…”

Granum-Inspired Photoenzyme-Coupled Catalytic System via Stacked Polymeric Carbon Nitride

“…Cascade catalysis, featured by the elevated product diversity and the overall transformation yield, has emerged as an efficient and generic approach to the synthesis of a variety of chemicals. − As a typical cascade catalytic process, photoenzyme-coupled catalysis combines the light absorption capability of semiconductors with the complementary activity and superior regio-/stereospecificity of enzymes, which has become a promising and multipurpose platform for green chemical manufacturing. − Currently, photoenzyme-coupled catalysis is being used to efficiently and precisely activate a number of chemical bonds, including CO, C–H, C–C, and CC. Accordingly, a number of photoenzyme-coupled reaction routes, including carbon dioxide (CO 2 ) conversion, chiral alcohol synthesis, and chiral amino acid production, have been explored. − In general, a photoenzyme-coupled reaction is composed of a photocatalytic module and an enzymatic module. In the photoenzyme-coupled catalysis, energy-bearing intermediates, such as NAD + /NADH, NADP + /NADPH, FAD 2+ /FADH 2, and O 2 /H 2 O 2, − could be regenerated by photocatalysis and utilized by enzymatic catalysis.…”

Metal Hydride-Embedded Titania Coating to Coordinate Electron Transfer and Enzyme Protection in Photo-enzymatic Catalysis

“…Breaking the boundaries of different catalytic processes could spur the generation of novel catalytic systems. Photo-enzymatic coupled systems (PECSs) integrate a synthetic photocatalyst and a natural enzyme, which promise the selective solar-to-chemical conversion and exploration of non-natural reactivity of enzymes. − As compared with natural pigments, synthetic photocatalysts display several superiorities such as higher stability, controlled absorption spectra, etc . Particularly, semiconductor photocatalysts, including silicon, perovskite, cadmium sulfide, black phosphorus, etc.…”