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
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	asymmetric synthesis flavanols kinetic resolution lipases Mitsunobu reaction Chemical technology TP1-1185 Chemistry QD1-999
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
work_keys_str_mv	AT martinsoto chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions AT irenesanzmachin chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions AT humbertorodriguezsolla chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions AT vicentegotorfernandez chemoenzymaticstereoselectivesynthesisofitransiflavan4olsvialipasecatalyzedkineticresolutions
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Chemoenzymatic Stereoselective Synthesis of <i>trans</i>-Flavan-4-ols via Lipase-Catalyzed Kinetic Resolutions

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