Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation

Abstract:

Chiral 2-substituted 3-hydroxycarboxylic acid derivatives are valuable building blocks for the preparation of naturally occurring and synthetic biologically active molecules. Current methodologies for the preparation of these compounds are still limited for large-scale production due to the high costs, limited microbial strains, low yields, difficult downstream processing, and limited range of structures. We report an effective chemoenzymatic method for the synthesis of enantiomerically pure 2 substituted 3 hydroxycarboxylic esters. The strategy comprises: i) a stereoselective aldol addition of 2 oxoacids to methanal catalyzed by two enantiocomplementary 2 oxoacid aldolases, ii) oxidative decarboxylation, and iii) esterification. Compounds with S-configuration were obtained in 69-80% isolated yields (94-99% ee), and the R enantiomers in 57-88% (88-95% ee), using a substrate concentration range of 0.1-1.0 M. The method developed offers a versatile alternative route to this important class of chiral building blocks, and highlights the exciting opportunities available for using natural enzymes with minimal active site modification.

SEEK ID: https://fairdomhub.org/publications/418

DOI: 10.1021/acscatal.9b01646

Projects: TRALAMINOL

Publication type: Not specified

Journal: ACS Catal.

Citation: ACS Catal.

Date Published: 8th Jul 2019

Registered Mode: Not specified

Authors: Roser Marín-Valls, Karel Hernández, Michael Bolte, Jesús Joglar, Jordi Bujons, Pere Clapés

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Citation
Marín-Valls, R., Hernández, K., Bolte, M., Joglar, J., Bujons, J., & Clapés, P. (2019). Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation. In ACS Catalysis (Vol. 9, Issue 8, pp. 7568–7577). American Chemical Society (ACS). https://doi.org/10.1021/acscatal.9b01646
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Created: 17th Jul 2019 at 15:39

Last updated: 17th Jul 2019 at 15:49

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