Enantioselective Aldol Addition of Acetaldehyde to Aromatic Aldehydes Catalyzed by Proline-Based Carboligases.


Journal

ACS catalysis
ISSN: 2155-5435
Titre abrégé: ACS Catal
Pays: United States
ID NLM: 101562209

Informations de publication

Date de publication:
21 Feb 2020
Historique:
received: 03 01 2020
revised: 27 01 2020
entrez: 3 3 2020
pubmed: 3 3 2020
medline: 3 3 2020
Statut: ppublish

Résumé

Aromatic β-hydroxyaldehydes, 1,3-diols, and α,β-unsaturated aldehydes are valuable precursors to biologically active natural products and drug molecules. Herein we report the biocatalytic aldol condensation of acetaldehyde with various aromatic aldehydes to give a number of aromatic α,β-unsaturated aldehydes using a previously engineered variant of 4-oxalocrotonate tautomerase [4-OT(M45T/F50A)] as carboligase. Moreover, an efficient one-pot two-step chemoenzymatic route toward chiral aromatic 1,3-diols has been developed. This one-pot chemoenzymatic strategy successfully combined a highly enantioselective aldol addition step catalyzed by a proline-based carboligase [4-OT(M45T/F50A) or TAUT015] with a chemical reduction step to convert enzymatically prepared aromatic β-hydroxyaldehydes into the corresponding 1,3-diols with high optical purity (e.r. up to >99:1) and in good isolated yield (51-92%). These developed (chemo)enzymatic methodologies offer alternative synthetic choices to prepare a variety of important drug precursors.

Identifiants

pubmed: 32117575
doi: 10.1021/acscatal.0c00039
pmc: PMC7045556
doi:

Types de publication

Journal Article

Langues

eng

Pagination

2522-2527

Informations de copyright

Copyright © 2020 American Chemical Society.

Déclaration de conflit d'intérêts

The authors declare no competing financial interest.

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Auteurs

Mohammad Saifuddin (M)

Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Chao Guo (C)

Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Lieuwe Biewenga (L)

Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Thangavelu Saravanan (T)

Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Simon J Charnock (SJ)

Prozomix Ltd., Station Court, Haltwhistle, Northumberland NE49 9HN, U.K.

Gerrit J Poelarends (GJ)

Department of Chemical and Pharmaceutical Biology, Groningen Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV Groningen, The Netherlands.

Classifications MeSH