Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition-Transamination Reactions
Moreno, Carlos J. (Institut de Química Avançada de Catalunya)
Hernández, Karel (Institut de Química Avançada de Catalunya)
Charnok, Simon J. (Prozomix Limited West End Industrial Estate)
Gittings, Samantha (Prozomix Limited West End Industrial Estate)
Bolte, Michael (Goethe-Universität Frankfurt am Main)
Joglar, Jesús (Institut de Química Avançada de Catalunya)
Bujons, Jordi (Institut de Química Avançada de Catalunya)
Parella Coll, Teodor (Universitat Autònoma de Barcelona. Servei de Ressonància Magnètica Nuclear)
Clapés, Pere (Institut de Química Avançada de Catalunya)

Data:	2021
Resum:	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) -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) -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 -Asp as a substrate to regenerate -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.
Ajuts:	Agencia Estatal de Investigación RTI2018-094637-B-I00 Agencia Estatal de Investigación PGC2018-095808-B-I00 Agencia Estatal de Investigación PCI2018-092937 European Commission 722361
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Biocatalysis ; 2-oxoacid aldolase ; Transaminases ; Aldol addition ; Reductive amination ; Γ-hydroxy-α-amino acids
Publicat a:	ACS catalysis, Vol. 11, Issue 8 (April 2021) , p. 4660-4669, ISSN 2155-5435

DOI: 10.1021/acscatal.1c00210
PMID: 34603828

10 p, 4.0 MB

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