Cargando…

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

[Image: see text] 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 pyru...

Descripción completa

Detalles Bibliográficos
Autores principales: Moreno, Carlos J., Hernández, Karel, Charnok, Simon J., Gittings, Samantha, Bolte, Michael, Joglar, Jesús, Bujons, Jordi, Parella, Teodor, Clapés, Pere
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2021
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482765/
https://www.ncbi.nlm.nih.gov/pubmed/34603828
http://dx.doi.org/10.1021/acscatal.1c00210
_version_ 1784576978689458176
author Moreno, Carlos J.
Hernández, Karel
Charnok, Simon J.
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés, Pere
author_facet Moreno, Carlos J.
Hernández, Karel
Charnok, Simon J.
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés, Pere
author_sort Moreno, Carlos J.
collection PubMed
description [Image: see text] 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.
format Online
Article
Text
id pubmed-8482765
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher American Chemical Society
record_format MEDLINE/PubMed
spelling pubmed-84827652021-10-01 Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions Moreno, Carlos J. Hernández, Karel Charnok, Simon J. Gittings, Samantha Bolte, Michael Joglar, Jesús Bujons, Jordi Parella, Teodor Clapés, Pere ACS Catal [Image: see text] 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. American Chemical Society 2021-04-02 2021-04-16 /pmc/articles/PMC8482765/ /pubmed/34603828 http://dx.doi.org/10.1021/acscatal.1c00210 Text en © 2021 American Chemical Society https://creativecommons.org/licenses/by/4.0/Permits the broadest form of re-use including for commercial purposes, provided that author attribution and integrity are maintained (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Moreno, Carlos J.
Hernández, Karel
Charnok, Simon J.
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés, Pere
Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_full Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_fullStr Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_full_unstemmed Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_short Synthesis of γ-Hydroxy-α-amino Acid Derivatives by Enzymatic Tandem Aldol Addition–Transamination Reactions
title_sort synthesis of γ-hydroxy-α-amino acid derivatives by enzymatic tandem aldol addition–transamination reactions
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8482765/
https://www.ncbi.nlm.nih.gov/pubmed/34603828
http://dx.doi.org/10.1021/acscatal.1c00210
work_keys_str_mv AT morenocarlosj synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT hernandezkarel synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT charnoksimonj synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT gittingssamantha synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT boltemichael synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT joglarjesus synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT bujonsjordi synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT parellateodor synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions
AT clapespere synthesisofghydroxyaaminoacidderivativesbyenzymatictandemaldoladditiontransaminationreactions