Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
| Autor: | Samantha Gittings, Jesús Joglar, Pere Clapés, Jordi Bujons, Simon J. Charnok, Karel Hernández, Carlos J. Moreno, Teodor Parella, Michael Bolte |
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| Přispěvatelé: | Ministerio de Ciencia e Innovación (España), European Commission, Clapés Saborit, Pere [0000-0001-5541-4794], Clapés Saborit, Pere |
| Rok vydání: | 2021 |
| Předmět: |
Transamination
Stereochemistry 010402 general chemistry 01 natural sciences Catalysis Benzaldehyde chemistry.chemical_compound Benzylamine Aldol reaction Benzoin Transaminases chemistry.chemical_classification γ-hydroxy-α-amino acids 010405 organic chemistry 2-oxoacid aldolases Enantioselective synthesis General Chemistry Aldol addition 0104 chemical sciences Amino acid aldol addition Aldol adittion chemistry Biocatalysis Reductive amination 2-oxoacid aldolase Research Article |
| Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname Dipòsit Digital de Documents de la UAB Universitat Autònoma de Barcelona ACS Catalysis |
| Popis: | 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. This project has received funding from the Ministerio de Ciencia e Innovación (MICIN), cofinanced by the Fondo Europeo de Desarrollo Regional (FEDER) (grants RTI2018-094637-B-I00 to P.C. and PGC2018-095808-B-I00 to T.P.), and Programación Conjunta Internacional (PCI2018-092937), through the EU initiative ERA CoBioTech under grant agreement No [722361] to P.C and S.J.Ch.) (Tralaminol). |
| Databáze: | OpenAIRE |
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