Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions

Flavan-4-ols are a subclass of flavonoids that are present in complex molecules with application in the industrial sector as pigments, antioxidants, or antimitotics, among many others. The most traditional way to achieve their synthesis is from naturally abundant flavanones, asymmetric transfer hydr...

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Autores principales: Martín Soto, Irene Sanz-Machín, Humberto Rodríguez-Solla, Vicente Gotor-Fernández
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Publicado: MDPI AG 2021
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Acceso en línea:https://doaj.org/article/0248bf19714140ab9e237dc11bf5b0a8
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spelling oai:doaj.org-article:0248bf19714140ab9e237dc11bf5b0a82021-11-25T17:05:34ZChemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions10.3390/catal111112962073-4344https://doaj.org/article/0248bf19714140ab9e237dc11bf5b0a82021-10-01T00:00:00Zhttps://www.mdpi.com/2073-4344/11/11/1296https://doaj.org/toc/2073-4344Flavan-4-ols are a subclass of flavonoids that are present in complex molecules with application in the industrial sector as pigments, antioxidants, or antimitotics, among many others. The most traditional way to achieve their synthesis is from naturally abundant flavanones, asymmetric transfer hydrogenation reactions or bioreduction being well known strategies, while their preparation from racemic flavan-4-ols has been less explored. In this article, we have focused on the synthesis of a series of <i>trans</i>-flavan-4-ols bearing different substitution patterns in the aromatic ring to explore later the potential of lipases as biocatalysts for stereoselective acylation reactions. Therefore, a series of flavanones have been chemically prepared, starting from the corresponding benzaldehydes by aldol condensation with 2′-hydroxyacetophenone in a strongly basic medium, and later transformed into the corresponding racemic <i>trans</i>-flavan-4-ols following a carbonyl reduction, Mitsunobu reaction, and ester deprotection sequence. A screening of lipases and optimization of the reaction conditions for the stereoselective acylation of racemic 2-phenylchroman-4-ol were performed before expanding the best reaction conditions to the kinetic resolution of other 2-arylchroman-4-ols. Interestingly, the combination of AK lipase from <i>Pseudomonas fluorescens</i> as enzyme and vinyl acetate as both acyl donor and solvent allowed the performance of highly asymmetric transformations (<i>E</i> > 200, 50–99% <i>ee<sub>S</sub></i> and >99% <i>ee<sub>P</sub></i>) under mild reaction conditions (30 °C and 250 rpm).Martín SotoIrene Sanz-MachínHumberto Rodríguez-SollaVicente Gotor-FernándezMDPI AGarticleasymmetric synthesisflavanolskinetic resolutionlipasesMitsunobu reactionChemical technologyTP1-1185ChemistryQD1-999ENCatalysts, Vol 11, Iss 1296, p 1296 (2021)
institution DOAJ
collection DOAJ
language EN
topic asymmetric synthesis
flavanols
kinetic resolution
lipases
Mitsunobu reaction
Chemical technology
TP1-1185
Chemistry
QD1-999
spellingShingle asymmetric synthesis
flavanols
kinetic resolution
lipases
Mitsunobu reaction
Chemical technology
TP1-1185
Chemistry
QD1-999
Martín Soto
Irene Sanz-Machín
Humberto Rodríguez-Solla
Vicente Gotor-Fernández
Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions
description Flavan-4-ols are a subclass of flavonoids that are present in complex molecules with application in the industrial sector as pigments, antioxidants, or antimitotics, among many others. The most traditional way to achieve their synthesis is from naturally abundant flavanones, asymmetric transfer hydrogenation reactions or bioreduction being well known strategies, while their preparation from racemic flavan-4-ols has been less explored. In this article, we have focused on the synthesis of a series of <i>trans</i>-flavan-4-ols bearing different substitution patterns in the aromatic ring to explore later the potential of lipases as biocatalysts for stereoselective acylation reactions. Therefore, a series of flavanones have been chemically prepared, starting from the corresponding benzaldehydes by aldol condensation with 2′-hydroxyacetophenone in a strongly basic medium, and later transformed into the corresponding racemic <i>trans</i>-flavan-4-ols following a carbonyl reduction, Mitsunobu reaction, and ester deprotection sequence. A screening of lipases and optimization of the reaction conditions for the stereoselective acylation of racemic 2-phenylchroman-4-ol were performed before expanding the best reaction conditions to the kinetic resolution of other 2-arylchroman-4-ols. Interestingly, the combination of AK lipase from <i>Pseudomonas fluorescens</i> as enzyme and vinyl acetate as both acyl donor and solvent allowed the performance of highly asymmetric transformations (<i>E</i> > 200, 50–99% <i>ee<sub>S</sub></i> and >99% <i>ee<sub>P</sub></i>) under mild reaction conditions (30 °C and 250 rpm).
format article
author Martín Soto
Irene Sanz-Machín
Humberto Rodríguez-Solla
Vicente Gotor-Fernández
author_facet Martín Soto
Irene Sanz-Machín
Humberto Rodríguez-Solla
Vicente Gotor-Fernández
author_sort Martín Soto
title Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions
title_short Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions
title_full Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions
title_fullStr Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions
title_full_unstemmed Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions
title_sort chemoenzymatic stereoselective synthesis of <i>trans</i>-flavan-4-ols via lipase-catalyzed kinetic resolutions
publisher MDPI AG
publishDate 2021
url https://doaj.org/article/0248bf19714140ab9e237dc11bf5b0a8
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AT irenesanzmachin chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions
AT humbertorodriguezsolla chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions
AT vicentegotorfernandez chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions
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