Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester
2,3-dihydroxy-2-methylbutyric acid, also known as 2,3-dimethylglyceric acid, constitutes the acyl and/or the alcoholic moiety of many bioactive natural esters. Herein, we describe a chemoenzymatic methodology which gives access to all the four possible stereoisomers of the 2,3-dimethylglyceric acid...
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2021
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Online Access: | https://hdl.handle.net/11392/2468959 https://doi.org/10.3390/catal11121440 https://www.mdpi.com/2073-4344/11/12/1440 |
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ftunivferrarair:oai:iris.unife.it:11392/2468959 2024-02-11T09:57:16+01:00 Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester Presini, Francesco Di Carmine, Graziano Giovannini, Pier Paolo Cristofori, Virginia Lerin, Lindomar Alberto Bortolini, Olga Trapella, Claudio Fantinati, Anna Presini, Francesco Di Carmine, Graziano Giovannini, Pier Paolo Cristofori, Virginia Lerin, Lindomar Alberto Bortolini, Olga Trapella, Claudio Fantinati, Anna 2021 ELETTRONICO https://hdl.handle.net/11392/2468959 https://doi.org/10.3390/catal11121440 https://www.mdpi.com/2073-4344/11/12/1440 eng eng info:eu-repo/semantics/altIdentifier/wos/WOS:000735927800001 volume:11 issue:12 firstpage:1440-1 lastpage:1440-10 numberofpages:10 journal:CATALYSTS https://hdl.handle.net/11392/2468959 doi:10.3390/catal11121440 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85119915586 https://www.mdpi.com/2073-4344/11/12/1440 info:eu-repo/semantics/openAccess biocatalysis stereodivergent synthesis asymmetric synthesis natural compounds info:eu-repo/semantics/article 2021 ftunivferrarair https://doi.org/10.3390/catal11121440 2024-01-24T17:44:09Z 2,3-dihydroxy-2-methylbutyric acid, also known as 2,3-dimethylglyceric acid, constitutes the acyl and/or the alcoholic moiety of many bioactive natural esters. Herein, we describe a chemoenzymatic methodology which gives access to all the four possible stereoisomers of the 2,3-dimethylglyceric acid ethyl ester. The racemic ethyl α-acetolactate, produced by the N-heterocycle carbene (NHC)-catalyzed coupling of ethyl pyruvate and methylacetoin was employed as the starting material. The racemic mixture was resolved through (S)-selective reductions, promoted by the acetylacetoin reductase (AAR) affording the resulting ethyl (2R,3S)-2,3-dimethylglycerate; the isolated remaining (S)-ethyl α-acetolactate was successively treated with baker’s yeast to obtain the corresponding (2S,3S) stereoisomer. syn-2,3-Dimethylgliceric acid ethyl ester afforded by reducing the rac-α-acetolactate with NaBH4 in the presence of ZnCl2 was kinetically resolved through selective acetylation with lipase B from Candida antarctica (CAL-B) and vinyl acetate to access to (2S,3R) stereoisomer. Finally, the (2R,3R) stereoisomer, was prepared by C3 epimerization of the (2R,3S) stereoisomer recovered from the above kinetic resolution, achieved through the TEMPO-mediated oxidation, followed by the reduction of the produced ketone with NaBH4. The resulting 2,3-dimethylglycertate enriched in the (2R,3R) stereoisomer was submitted to stereospecicific acetylation with vinyl acetate and CAL-B in order to separate the major stereoisomer. The entire procedure enabled conversion of the racemic α-acetolactate into the four enantiopure stereoisomers of the ethyl 2,3-dihydroxy-2-methylbutyrate with the following overall yields: 42% for the (2R,3S), 40% for the (2S,3S), 42% for the (2S,3R) and 20% for the (2R,3R). Article in Journal/Newspaper Antarc* Antarctica Università degli Studi di Ferrara: CINECA IRIS Catalysts 11 12 1440 |
institution |
Open Polar |
collection |
Università degli Studi di Ferrara: CINECA IRIS |
op_collection_id |
ftunivferrarair |
language |
English |
topic |
biocatalysis stereodivergent synthesis asymmetric synthesis natural compounds |
spellingShingle |
biocatalysis stereodivergent synthesis asymmetric synthesis natural compounds Presini, Francesco Di Carmine, Graziano Giovannini, Pier Paolo Cristofori, Virginia Lerin, Lindomar Alberto Bortolini, Olga Trapella, Claudio Fantinati, Anna Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester |
topic_facet |
biocatalysis stereodivergent synthesis asymmetric synthesis natural compounds |
description |
2,3-dihydroxy-2-methylbutyric acid, also known as 2,3-dimethylglyceric acid, constitutes the acyl and/or the alcoholic moiety of many bioactive natural esters. Herein, we describe a chemoenzymatic methodology which gives access to all the four possible stereoisomers of the 2,3-dimethylglyceric acid ethyl ester. The racemic ethyl α-acetolactate, produced by the N-heterocycle carbene (NHC)-catalyzed coupling of ethyl pyruvate and methylacetoin was employed as the starting material. The racemic mixture was resolved through (S)-selective reductions, promoted by the acetylacetoin reductase (AAR) affording the resulting ethyl (2R,3S)-2,3-dimethylglycerate; the isolated remaining (S)-ethyl α-acetolactate was successively treated with baker’s yeast to obtain the corresponding (2S,3S) stereoisomer. syn-2,3-Dimethylgliceric acid ethyl ester afforded by reducing the rac-α-acetolactate with NaBH4 in the presence of ZnCl2 was kinetically resolved through selective acetylation with lipase B from Candida antarctica (CAL-B) and vinyl acetate to access to (2S,3R) stereoisomer. Finally, the (2R,3R) stereoisomer, was prepared by C3 epimerization of the (2R,3S) stereoisomer recovered from the above kinetic resolution, achieved through the TEMPO-mediated oxidation, followed by the reduction of the produced ketone with NaBH4. The resulting 2,3-dimethylglycertate enriched in the (2R,3R) stereoisomer was submitted to stereospecicific acetylation with vinyl acetate and CAL-B in order to separate the major stereoisomer. The entire procedure enabled conversion of the racemic α-acetolactate into the four enantiopure stereoisomers of the ethyl 2,3-dihydroxy-2-methylbutyrate with the following overall yields: 42% for the (2R,3S), 40% for the (2S,3S), 42% for the (2S,3R) and 20% for the (2R,3R). |
author2 |
Presini, Francesco Di Carmine, Graziano Giovannini, Pier Paolo Cristofori, Virginia Lerin, Lindomar Alberto Bortolini, Olga Trapella, Claudio Fantinati, Anna |
format |
Article in Journal/Newspaper |
author |
Presini, Francesco Di Carmine, Graziano Giovannini, Pier Paolo Cristofori, Virginia Lerin, Lindomar Alberto Bortolini, Olga Trapella, Claudio Fantinati, Anna |
author_facet |
Presini, Francesco Di Carmine, Graziano Giovannini, Pier Paolo Cristofori, Virginia Lerin, Lindomar Alberto Bortolini, Olga Trapella, Claudio Fantinati, Anna |
author_sort |
Presini, Francesco |
title |
Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester |
title_short |
Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester |
title_full |
Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester |
title_fullStr |
Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester |
title_full_unstemmed |
Chemoenzymatic Stereodivergent Synthesis of All the Possible Stereoisomers of the 2,3-Dimethylglyceric Acid Ethyl Ester |
title_sort |
chemoenzymatic stereodivergent synthesis of all the possible stereoisomers of the 2,3-dimethylglyceric acid ethyl ester |
publishDate |
2021 |
url |
https://hdl.handle.net/11392/2468959 https://doi.org/10.3390/catal11121440 https://www.mdpi.com/2073-4344/11/12/1440 |
genre |
Antarc* Antarctica |
genre_facet |
Antarc* Antarctica |
op_relation |
info:eu-repo/semantics/altIdentifier/wos/WOS:000735927800001 volume:11 issue:12 firstpage:1440-1 lastpage:1440-10 numberofpages:10 journal:CATALYSTS https://hdl.handle.net/11392/2468959 doi:10.3390/catal11121440 info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-85119915586 https://www.mdpi.com/2073-4344/11/12/1440 |
op_rights |
info:eu-repo/semantics/openAccess |
op_doi |
https://doi.org/10.3390/catal11121440 |
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Catalysts |
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