Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction

Chiral 2-hydroxy acids and 2-hydroxy-4-butyrolactone derivatives are structural motifs often found in fine and commodity chemicals. Here, we report a tandem biocatalytic stereodivergent route for the preparation of these compounds using three stereoselective aldolases and two stereocomplementary ket...

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Detalles Bibliográficos
Autores: Moreno, Carlos J., Hernández, Karel, Gittings, Samantha, Bolte, Michael, Joglar, Jesús, Bujons, Jordi, Parella, Teodor, Clapés Saborit, Pere
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Consejo Superior de Investigaciones Científicas (CSIC)
Repositorio:DIGITAL.CSIC. Repositorio Institucional del CSIC
OAI Identifier:oai:digital.csic.es:10261/307046
Acceso en línea:http://hdl.handle.net/10261/307046
https://api.elsevier.com/content/abstract/scopus_id/85152201605
Access Level:acceso abierto
Palabra clave:Ketoreductases
2-hydroxy acids
2-hydroxy-4-butyrolactones
2-oxoacid aldolase
Aldol addition
Biocatalysis
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
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spelling Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl ReductionMoreno, Carlos J.Hernández, KarelGittings, SamanthaBolte, MichaelJoglar, JesúsBujons, JordiParella, TeodorClapés Saborit, PereKetoreductases2-hydroxy acids2-hydroxy-4-butyrolactones2-oxoacid aldolaseAldol additionBiocatalysishttp://metadata.un.org/sdg/3Ensure healthy lives and promote well-being for all at all agesChiral 2-hydroxy acids and 2-hydroxy-4-butyrolactone derivatives are structural motifs often found in fine and commodity chemicals. Here, we report a tandem biocatalytic stereodivergent route for the preparation of these compounds using three stereoselective aldolases and two stereocomplementary ketoreductases using simple and achiral starting materials. The strategy comprises (i) aldol addition reaction of 2-oxoacids to aldehydes using two aldolases from E. coli, 3-methyl-2-oxobutanoate hydroxymethyltransferase (KPHMTEcoli), 2-keto-3-deoxy-l-rhamnonate aldolase (YfaUEcoli), and trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida (HBPAPputida) and (ii) subsequent 2-oxogroup reduction of the aldol adduct by ketopantoate reductase from E. coli (KPREcoli) and a Δ1-piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkAPsyrin) with uncovered promiscuous ketoreductase activity. A total of 29 structurally diverse compounds were prepared: both enantiomers of 2-hydroxy-4-butyrolactone (>99% ee), 21 2-hydroxy-3-substituted-4-butyrolactones with the (2R,3S), (2S,3S), (2R,3R), or (2S,3R) configuration (from 60:40 to 98:2 dr), and 6 2-hydroxy-4-substituted-4-butyrolactones with the (2S,4R) configuration (from 87:13 to 98:2 dr). Conversions of aldol adducts varied from 32 to 98%, while quantitative conversions were achieved by both ketoreductases, with global isolated yields between 20 and 45% for most of the examples. One-pot one-step cascade reactions were successfully conducted achieving isolated yields from 30 to 57%.Grant PID2021-122166OB-I00 funded by MCIN/AEI/10.13039/501100011033 and “ERDF A way of making Europe”. C.J.M. acknowledges a PhD contract (i.e., Ayudas para Contratos Predoctorales para la Formación de Doctores) BES-2016-079447 funded by MCIN/AEI/10.13039/501100011033. The authors wish to thank Dr. Lothar Fink, from Frankfurt University, for the X-ray structure determination with Cu Kα radiation. The authors thankfully acknowledge the use of the computational resources of the Consorci de Serveis Universitaris de Catalunya (CSUC).Peer reviewedAmerican Chemical SocietyMinisterio de Ciencia e Innovación (España)Bujons, Jordi [0000-0003-2944-2905]Parella, Teodor [0000-0002-1914-2709]Clapés Saborit, Pere [0000-0001-5541-4794]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202320232023info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/307046https://api.elsevier.com/content/abstract/scopus_id/85152201605reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122166OB-I00info:eu-repo/grantAgreement/AEI//BES-2016-079447https://doi.org/10.1021/acscatal.3c00367Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3070462026-05-22T06:33:51Z
dc.title.none.fl_str_mv Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
spellingShingle Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
Moreno, Carlos J.
Ketoreductases
2-hydroxy acids
2-hydroxy-4-butyrolactones
2-oxoacid aldolase
Aldol addition
Biocatalysis
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
title_short Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_full Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_fullStr Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_full_unstemmed Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_sort Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
dc.creator.none.fl_str_mv Moreno, Carlos J.
Hernández, Karel
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés Saborit, Pere
author Moreno, Carlos J.
author_facet Moreno, Carlos J.
Hernández, Karel
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés Saborit, Pere
author_role author
author2 Hernández, Karel
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés Saborit, Pere
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
Bujons, Jordi [0000-0003-2944-2905]
Parella, Teodor [0000-0002-1914-2709]
Clapés Saborit, Pere [0000-0001-5541-4794]
Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]
dc.subject.none.fl_str_mv Ketoreductases
2-hydroxy acids
2-hydroxy-4-butyrolactones
2-oxoacid aldolase
Aldol addition
Biocatalysis
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
topic Ketoreductases
2-hydroxy acids
2-hydroxy-4-butyrolactones
2-oxoacid aldolase
Aldol addition
Biocatalysis
http://metadata.un.org/sdg/3
Ensure healthy lives and promote well-being for all at all ages
description Chiral 2-hydroxy acids and 2-hydroxy-4-butyrolactone derivatives are structural motifs often found in fine and commodity chemicals. Here, we report a tandem biocatalytic stereodivergent route for the preparation of these compounds using three stereoselective aldolases and two stereocomplementary ketoreductases using simple and achiral starting materials. The strategy comprises (i) aldol addition reaction of 2-oxoacids to aldehydes using two aldolases from E. coli, 3-methyl-2-oxobutanoate hydroxymethyltransferase (KPHMTEcoli), 2-keto-3-deoxy-l-rhamnonate aldolase (YfaUEcoli), and trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida (HBPAPputida) and (ii) subsequent 2-oxogroup reduction of the aldol adduct by ketopantoate reductase from E. coli (KPREcoli) and a Δ1-piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkAPsyrin) with uncovered promiscuous ketoreductase activity. A total of 29 structurally diverse compounds were prepared: both enantiomers of 2-hydroxy-4-butyrolactone (>99% ee), 21 2-hydroxy-3-substituted-4-butyrolactones with the (2R,3S), (2S,3S), (2R,3R), or (2S,3R) configuration (from 60:40 to 98:2 dr), and 6 2-hydroxy-4-substituted-4-butyrolactones with the (2S,4R) configuration (from 87:13 to 98:2 dr). Conversions of aldol adducts varied from 32 to 98%, while quantitative conversions were achieved by both ketoreductases, with global isolated yields between 20 and 45% for most of the examples. One-pot one-step cascade reactions were successfully conducted achieving isolated yields from 30 to 57%.
publishDate 2023
dc.date.none.fl_str_mv 2023
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
http://purl.org/coar/resource_type/c_6501
Publisher's version
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/307046
https://api.elsevier.com/content/abstract/scopus_id/85152201605
url http://hdl.handle.net/10261/307046
https://api.elsevier.com/content/abstract/scopus_id/85152201605
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
#PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122166OB-I00
info:eu-repo/grantAgreement/AEI//BES-2016-079447
https://doi.org/10.1021/acscatal.3c00367
Sí
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv American Chemical Society
publisher.none.fl_str_mv American Chemical Society
dc.source.none.fl_str_mv reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC
instname:Consejo Superior de Investigaciones Científicas (CSIC)
instname_str Consejo Superior de Investigaciones Científicas (CSIC)
reponame_str DIGITAL.CSIC. Repositorio Institucional del CSIC
collection DIGITAL.CSIC. Repositorio Institucional del CSIC
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15.812429

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