Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes

Abstract:

The congested nature of quaternary carbons hinders their preparation, most notably when stereocontrol is required. Here we report a biocatalytic method for the creation of quaternary carbon centers with broad substrate scope, leading to different compound classes bearing this structural feature. The key step comprises the aldol addition of 3,3-disubstituted 2-oxoacids to aldehydes catalyzed by metal dependent 3-methyl-2-oxobutanoate hydroxymethyltransferase from E. coli (KPHMT) and variants thereof. The 3,3,3-trisubstituted 2-oxoacids thus produced were converted into 2-oxolactones and 3-hydroxy acids and directly to ulosonic acid derivatives, all bearing gem-dialkyl, gem-cycloalkyl, and spirocyclic quaternary centers. In addition, some of these reactions use a single enantiomer from racemic nucleophiles to afford stereopure quaternary carbons. The notable substrate tolerance and stereocontrol of these enzymes are indicative of their potential for the synthesis of structurally intricate molecules.

SEEK ID: https://fairdomhub.org/publications/583

DOI: 10.1021/jacs.0c09994

Projects: TRALAMINOL

Publication type: Journal

Journal: Journal of the American Chemical Society

Citation: J. Am. Chem. Soc. 142(46):19754-19762

Date Published: 18th Nov 2020

Registered Mode: by DOI

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

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Citation
Marín-Valls, R., Hernández, K., Bolte, M., Parella, T., Joglar, J., Bujons, J., & Clapés, P. (2020). Biocatalytic Construction of Quaternary Centers by Aldol Addition of 3,3-Disubstituted 2-Oxoacid Derivatives to Aldehydes. In Journal of the American Chemical Society (Vol. 142, Issue 46, pp. 19754–19762). American Chemical Society (ACS). https://doi.org/10.1021/jacs.0c09994
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Created: 26th Nov 2020 at 07:02

Last updated: 26th Nov 2020 at 07:04

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