Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition-Transamination Reactions.

Autor:	Moreno CJ; Institute for Advanced Chemistry of Catalonia, Department of Biological Chemistry, IQAC-CSIC, Jordi Girona 18-24, Barcelona 08034, Spain., Hernández K; Institute for Advanced Chemistry of Catalonia, Department of Biological Chemistry, IQAC-CSIC, Jordi Girona 18-24, Barcelona 08034, Spain., Charnok SJ; Prozomix Ltd. West End Industrial Estate, Haltwhistle, Northumberland NE49 9HA, U.K., Gittings S; Prozomix Ltd. West End Industrial Estate, Haltwhistle, Northumberland NE49 9HA, U.K., Bolte M; Institut für Anorganische Chemie, J.-W.-Goethe-Universität, Frankfurt/Main, Germany., Joglar J; Institute for Advanced Chemistry of Catalonia, Department of Biological Chemistry, IQAC-CSIC, Jordi Girona 18-24, Barcelona 08034, Spain., Bujons J; Institute for Advanced Chemistry of Catalonia, Department of Biological Chemistry, IQAC-CSIC, Jordi Girona 18-24, Barcelona 08034, Spain., Parella T; Servei de Ressonància Magnètica Nuclear, Universitat Autònoma de Barcelona, Bellaterra, Spain., Clapés P; Institute for Advanced Chemistry of Catalonia, Department of Biological Chemistry, IQAC-CSIC, Jordi Girona 18-24, Barcelona 08034, Spain.
Jazyk:	angličtina
Zdroj:	ACS catalysis [ACS Catal] 2021 Apr 16; Vol. 11 (8), pp. 4660-4669. Date of Electronic Publication: 2021 Apr 02.
DOI:	10.1021/acscatal.1c00210
Abstrakt:	Three enzymatic routes toward γ-hydroxy-α-amino acids by tandem aldol addition-transamination one-pot two-step reactions are reported. The approaches feature an enantioselective aldol addition of pyruvate to various nonaromatic aldehydes catalyzed by trans - o -hydroxybenzylidene pyruvate hydratase-aldolase (HBPA) from Pseudomonas putida . This affords chiral 4-hydroxy-2-oxo acids, which were subsequently enantioselectively aminated using S -selective transaminases. Three transamination processes were investigated involving different amine donors and transaminases: (i) l-Ala as an amine donor with pyruvate recycling, (ii) a benzylamine donor using benzaldehyde lyase from Pseudomonas fluorescens Biovar I (BAL) to transform the benzaldehyde formed into benzoin, minimizing equilibrium limitations, and (iii) l-Glu as an amine donor with a double cascade comprising branched-chain α-amino acid aminotransferase (BCAT) and aspartate amino transferase (AspAT), both from E. coli , using l-Asp as a substrate to regenerate l-Glu. The γ-hydroxy-α-amino acids thus obtained were transformed into chiral α-amino-γ-butyrolactones, structural motifs found in many biologically active compounds and valuable intermediates for the synthesis of pharmaceutical agents. Competing Interests: The authors declare no competing financial interest. (© 2021 American Chemical Society.)
Databáze:	MEDLINE
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