Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones

Autores
Kedziora, Kinga; Bisogno, Fabricio Román; Lavandera, Iván; Gotor-Fernández, Vicente; Montejo-Bernardo, Jose; García-Granda, Santiago; Kroutil, Wolfgang; Gotor, Vicente
Año de publicación
2014
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Fil: Kedziora, Kinga. Universidad de Oviedo; España
Fil: Bisogno, Fabricio Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad de Oviedo; España
Fil: Lavandera, Iván. Universidad de Oviedo; España
Fil: Gotor-Fernández, Vicente. Universidad de Oviedo; España
Fil: Montejo-Bernardo, Jose. Universidad de Oviedo; España
Fil: García-Granda, Santiago. Universidad de Oviedo; España
Fil: Kroutil, Wolfgang. University Of Graz; Austria
Fil: Gotor, Vicente. Universidad de Oviedo; España
Materia
ENANTIOSELECTIVITY
ENZYME CATALYSIS
HALOGENS
KETONES
REDUCTION
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/133184
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/133184
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketonesKedziora, KingaBisogno, Fabricio RománLavandera, IvánGotor-Fernández, VicenteMontejo-Bernardo, JoseGarcía-Granda, SantiagoKroutil, WolfgangGotor, VicenteENANTIOSELECTIVITYENZYME CATALYSISHALOGENSKETONESREDUCTIONhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Fil: Kedziora, Kinga. Universidad de Oviedo; EspañaFil: Bisogno, Fabricio Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad de Oviedo; EspañaFil: Lavandera, Iván. Universidad de Oviedo; EspañaFil: Gotor-Fernández, Vicente. Universidad de Oviedo; EspañaFil: Montejo-Bernardo, Jose. Universidad de Oviedo; EspañaFil: García-Granda, Santiago. Universidad de Oviedo; EspañaFil: Kroutil, Wolfgang. University Of Graz; AustriaFil: Gotor, Vicente. Universidad de Oviedo; EspañaWiley VCH Verlag2014-02info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/133184Kedziora, Kinga; Bisogno, Fabricio Román; Lavandera, Iván; Gotor-Fernández, Vicente; Montejo-Bernardo, Jose; et al.; Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones; Wiley VCH Verlag; Chemcatchem; 6; 4; 2-2014; 1066-10721867-38801867-3899CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.1002/cctc.201300834info:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cctc.201300834info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-10-15T14:36:20Zoai:ri.conicet.gov.ar:11336/133184instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-10-15 14:36:20.352CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
title Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
spellingShingle Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
Kedziora, Kinga
ENANTIOSELECTIVITY
ENZYME CATALYSIS
HALOGENS
KETONES
REDUCTION
title_short Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
title_full Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
title_fullStr Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
title_full_unstemmed Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
title_sort Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones
dc.creator.none.fl_str_mv Kedziora, Kinga
Bisogno, Fabricio Román
Lavandera, Iván
Gotor-Fernández, Vicente
Montejo-Bernardo, Jose
García-Granda, Santiago
Kroutil, Wolfgang
Gotor, Vicente
author Kedziora, Kinga
author_facet Kedziora, Kinga
Bisogno, Fabricio Román
Lavandera, Iván
Gotor-Fernández, Vicente
Montejo-Bernardo, Jose
García-Granda, Santiago
Kroutil, Wolfgang
Gotor, Vicente
author_role author
author2 Bisogno, Fabricio Román
Lavandera, Iván
Gotor-Fernández, Vicente
Montejo-Bernardo, Jose
García-Granda, Santiago
Kroutil, Wolfgang
Gotor, Vicente
author2_role author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ENANTIOSELECTIVITY
ENZYME CATALYSIS
HALOGENS
KETONES
REDUCTION
topic ENANTIOSELECTIVITY
ENZYME CATALYSIS
HALOGENS
KETONES
REDUCTION
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Fil: Kedziora, Kinga. Universidad de Oviedo; España
Fil: Bisogno, Fabricio Román. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Físico-química de Córdoba. Universidad Nacional de Córdoba. Facultad de Ciencias Químicas. Instituto de Investigaciones en Físico-química de Córdoba; Argentina. Universidad de Oviedo; España
Fil: Lavandera, Iván. Universidad de Oviedo; España
Fil: Gotor-Fernández, Vicente. Universidad de Oviedo; España
Fil: Montejo-Bernardo, Jose. Universidad de Oviedo; España
Fil: García-Granda, Santiago. Universidad de Oviedo; España
Fil: Kroutil, Wolfgang. University Of Graz; Austria
Fil: Gotor, Vicente. Universidad de Oviedo; España
description Alcohol dehydrogenases (ADHs) were identified as suitable enzymes for the reduction of the corresponding α,α-dihalogenated ketones, obtaining optically pure β,β-dichloro- or β,β-dibromohydrins with excellent conversions and enantiomeric excess. Among the different biocatalysts tested, ADHs from Rhodococcus ruber (ADH-A), Ralstonia sp. (RasADH), Lactobacillus brevis (LBADH), and PR2ADH proved to be the most efficient ones in terms of activity and stereoselectivity. In a further study, two racemic α-substituted ketones, namely α-bromo- α-chloro- and α-chloro-α-fluoroacetophenone were investigated to obtain one of the four possible diastereoisomers through a dynamic kinetic process. In the case of the brominated derivative, only the (1R)-enantiomer was obtained by using ADH-A, although with moderate diastereomeric excess (>99 % ee, 63 % de), whereas the fluorinated ketone exhibited a lower stereoselectivity (up to 45 % de). Bulking up: A series of β,β-dihalohydrins are obtained through alcohol dehydrogenase (ADH) catalyzed bioreduction of the synthesized α,α-dihalogenated ketones. Two racemic acetophenone derivatives are also subjected to this protocol to obtain stereoenriched alcohols through dynamic kinetic resolution (DKR). © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
publishDate 2014
dc.date.none.fl_str_mv 2014-02
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/133184
Kedziora, Kinga; Bisogno, Fabricio Román; Lavandera, Iván; Gotor-Fernández, Vicente; Montejo-Bernardo, Jose; et al.; Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones; Wiley VCH Verlag; Chemcatchem; 6; 4; 2-2014; 1066-1072
1867-3880
1867-3899
CONICET Digital
CONICET
url http://hdl.handle.net/11336/133184
identifier_str_mv Kedziora, Kinga; Bisogno, Fabricio Román; Lavandera, Iván; Gotor-Fernández, Vicente; Montejo-Bernardo, Jose; et al.; Expanding the scope of alcohol dehydrogenases towards bulkier substrates: Stereo- and enantiopreference for α,α-dihalogenated ketones; Wiley VCH Verlag; Chemcatchem; 6; 4; 2-2014; 1066-1072
1867-3880
1867-3899
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.1002/cctc.201300834
info:eu-repo/semantics/altIdentifier/url/https://chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/cctc.201300834
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Wiley VCH Verlag
publisher.none.fl_str_mv Wiley VCH Verlag
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
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score 13.22299

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