[Dataset] 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...

Descripción completa

Detalles Bibliográficos
Autores: Moreno, Carlos J., Hernández, Karel, Gittings, Samantha, Bolte, Michael, Joglar, Jesús, Bujons, Jordi, Parella, Teodor, Clapés, Pere
Tipo de recurso: conjunto de datos
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:10261/383941
Acceso en línea:http://hdl.handle.net/10261/383941
https://digital.csic.es/handle/10261/307046
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
id ES_9d129fc01716eeb74d092fdfbda6db71
oai_identifier_str oai:digital.csic.es:10261/383941
network_acronym_str ES
network_name_str España
repository_id_str
spelling [Dataset] 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, 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 (KPHMT Ecoli ), 2-keto-3-deoxy-l-rhamnonate aldolase (YfaU Ecoli ), and trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida (HBPA Pputida ) and (ii) subsequent 2-oxogroup reduction of the aldol adduct by ketopantoate reductase from E. coli (KPR Ecoli ) and a Δ1-piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkA Psyrin ) 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)0000-0003-2944-29050000-0002-1914-27090000-0001-5541-4794Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252023info:eu-repo/semantics/datasethttp://purl.org/coar/resource_type/c_ddb1http://hdl.handle.net/10261/383941https://digital.csic.es/handle/10261/307046reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/MCIN/AEI/10.13039ACS catalysisBiocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl ReductionSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/3839412026-05-22T06:33:51Z
dc.title.none.fl_str_mv [Dataset] Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title [Dataset] Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
spellingShingle [Dataset] 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 [Dataset] Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_full [Dataset] Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_fullStr [Dataset] Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_full_unstemmed [Dataset] Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
title_sort [Dataset] 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, Pere
author Moreno, Carlos J.
author_facet Moreno, Carlos J.
Hernández, Karel
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés, Pere
author_role author
author2 Hernández, Karel
Gittings, Samantha
Bolte, Michael
Joglar, Jesús
Bujons, Jordi
Parella, Teodor
Clapés, Pere
author2_role author
author
author
author
author
author
author
dc.contributor.none.fl_str_mv Ministerio de Ciencia e Innovación (España)
0000-0003-2944-2905
0000-0002-1914-2709
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 (KPHMT Ecoli ), 2-keto-3-deoxy-l-rhamnonate aldolase (YfaU Ecoli ), and trans-o-hydroxybenzylidene pyruvate hydratase-aldolase from Pseudomonas putida (HBPA Pputida ) and (ii) subsequent 2-oxogroup reduction of the aldol adduct by ketopantoate reductase from E. coli (KPR Ecoli ) and a Δ1-piperidine-2-carboxylate/Δ1-pyrroline-2-carboxylate reductase from Pseudomonas syringae pv. tomato DSM 50315 (DpkA Psyrin ) 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
2025
2025
dc.type.none.fl_str_mv info:eu-repo/semantics/dataset
http://purl.org/coar/resource_type/c_ddb1
format dataset
dc.identifier.none.fl_str_mv http://hdl.handle.net/10261/383941
https://digital.csic.es/handle/10261/307046
url http://hdl.handle.net/10261/383941
https://digital.csic.es/handle/10261/307046
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv #PLACEHOLDER_PARENT_METADATA_VALUE#
info:eu-repo/grantAgreement/MCIN/AEI/10.13039
ACS catalysis
Biocatalytic Synthesis of Homochiral 2-Hydroxy-4-butyrolactone Derivatives by Tandem Aldol Addition and Carbonyl Reduction
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
_version_ 1869414711877959680
score 15,81155

Similares en LA Referencia