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Fryszkowska A, Toogood H, Sakuma M, et al. Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation. Adv Synth Catal. 2009;351(17):2976-2990doi: 10.1002/adsc.200900603.
Fryszkowska, A., Toogood, H., Sakuma, M., Gardiner, J. M., Stephens, G. M., & Scrutton, N. S. (2009). Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation. Advanced synthesis & catalysis, 351(17), 2976-2990. https://doi.org/10.1002/adsc.200900603
Fryszkowska, Anna, et al. "Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation." Advanced synthesis & catalysis vol. 351,17 (2009): 2976-2990. doi: https://doi.org/10.1002/adsc.200900603
Fryszkowska A, Toogood H, Sakuma M, Gardiner JM, Stephens GM, Scrutton NS. Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation. Adv Synth Catal. 2009 Nov;351(17):2976-2990. doi: 10.1002/adsc.200900603. PMID: 20396613; PMCID: PMC2854813.
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Adv Synth Catal. 2009 Nov;351(17):2976-2990. doi: 10.1002/adsc.200900603.

Asymmetric Reduction of Activated Alkenes by Pentaerythritol Tetranitrate Reductase: Specificity and Control of Stereochemical Outcome by Reaction Optimisation.

Advanced synthesis & catalysis

Anna Fryszkowska, Helen Toogood, Michiyo Sakuma, John M Gardiner, Gill M Stephens, Nigel S Scrutton

Affiliations

  1. Manchester Interdisciplinary Biocentre, The School of Chemistry, The University of Manchester, 131 Princess Street, Manchester M1 7DN, U.K.

PMID: 20396613 PMCID: PMC2854813 DOI: 10.1002/adsc.200900603

Abstract

We show that pentaerythritol tetranitrate reductase (PETNR), a member of the 'ene' reductase old yellow enzyme family, catalyses the asymmetric reduction of a variety of industrially relevant activated alpha,beta-unsaturated alkenes including enones, enals, maleimides and nitroalkenes. We have rationalised the broad substrate specificity and stereochemical outcome of these reductions by reference to molecular models of enzyme-substrate complexes based on the crystal complex of the PETNR with 2-cyclohexenone 4a. The optical purity of products is variable (49-99% ee), depending on the substrate type and nature of substituents. Generally, high enantioselectivity was observed for reaction products with stereogenic centres at Cbeta (>99% ee). However, for the substrates existing in two isomeric forms (e.g., citral 11a or nitroalkenes 18-19a), an enantiodivergent course of the reduction of E/Z-forms may lead to lower enantiopurities of the products. We also demonstrate that the poor optical purity obtained for products with stereogenic centres at Calpha is due to non-enzymatic racemisation. In reactions with ketoisophorone 3a we show that product racemisation is prevented through reaction optimisation, specifically by shortening reaction time and through control of solution pH. We suggest this as a general strategy for improved recovery of optically pure products with other biocatalytic conversions where there is potential for product racemisation.

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