Chemoenzymatic Hydroxymethylation of Carboxylic Acids by Tandem Stereodivergent Biocatalytic Aldol Reaction and Chemical Decarboxylation
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 cos...
| Autores: | , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión aceptada para publicación |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/200847 |
| Acceso en línea: | http://hdl.handle.net/10261/200847 |
| Access Level: | acceso abierto |
| Palabra clave: | 2-keto-3-deoxy-l-rhamnonate aldolase (YfaU, EC 4.1.2.53) 2-oxoacid aldolases 2-oxoacids Aldol reaction 2-substituted 3-hydroxycarboxylic acids 3-methyl-2-oxobutanoate hydroxymethyltransferase (KPHMT, EC 2.1.2.11) Biocatalysis |
| Sumario: | 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% (88-98% 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. Copyright © 2019 American Chemical Society. |
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