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

Themes: Conversion

Keywords: Catalysis

Citation

Wang, Y.Huang, X., Hui, J., Vo, L.T.Zhao, H. July 24, 2020. “Stereoconvergent Reduction of Activated Alkenes by a Nicotinamide Free Synergistic Photobiocatalytic System.” ACS Catalysis. DOI: 10.1021/acscatal.0c02489.

Overview

Cooperative chemoenzymatic reactions. (a-c) Types of cooperative chemoenzymatic reactions. ER is the abbreviation of ene-reductase. “red” and “ox” indicate the reduction and oxidation state of the enzyme. (d) Combination of photoinduced electron transfer (PET), photosensitized energy transfer (PEnT), and enzymatic reduction of alkenes without using NAD(P)H. The asterisk indicates the chiral center; Ar, aryl; Chem Cat, chemical catalyst; PEnT, photosensitized energy transfer reaction; PET, photoinduced electron transfer reaction.

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.

Data

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  • Reaction development and condition optimization
  • Cofactor free, enzymatic reduction of (E)-1 or (Z)-1 with different photocatalysts and electron donors.
  • Enzymatic reduction of reactive isomers assisted by FAD-catalyzed SET and EDTA as electron donor under blue light.
  • Isomerization of less reactive isomers with Ir-16, FAD or both under blue light. a100 mM sodium phosphate buffer at pH 7.2 was used when using EDTA as electron donor. Other electron donors were dissolved in 10 mM CaCl2 with pH adjusted to 7.5
  • Enzymatic reduction with (E)-1 or (Z)-1 at different concentrations