Levetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities
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| Format: | Artículo científico |
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Universidade Estadual Paulista Júlio de Mesquita Filho
2022
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| author | Cintia Duarte de Freitas Milagre |
| author_facet | Cintia Duarte de Freitas Milagre |
| contents | Levetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities Cintia Duarte de Freitas Milagre Bruno Sergio do Amaral João Marcos Batista Junior Adriana Ferreira Lopes Vilela Carmen Lúcia Cardoso Humberto Marcio Santos Milagre Química alkylation heterocycles biocatalysis electronic circular dichroism (ECD) A chemoenzymatic approach for the synthesis of α-.-heterocyclic ethyl- and phenylacetamides, levetiracetam analogs, is described. Eight nitrile substrates were prepared through the .-alkylation of heterocycles (2-pyrrolidinone, 2-piperidinone, 2-oxopiperazine and 1-methylpiperazine) directly from hydroxyl group of ethyl and phenyl α-hydroxynitriles with yield of 35−71% after 12 h. Twenty nitrile hydratases (NHases) were screened and showed that the .-derivatives lactam substrates led to their correspondent amides by Co-type NHase with conversion and enantiomeric excess of up to 47.5 and 52.3% for (.)-enantiomer, while the piperazine substrates underwent spontaneous decomposition by retro-Strecker reaction. In order to avoid a retro-Strecker reaction of α-aminonitriles, ionic liquids and polyethylene glycol (PEG400) were evaluated as alternative green solvents to aqueous buffered solutions in different proportions. Temperature was another parameter investigated during reaction-medium engineering for process optimization. However, unconventional reaction media and low temperature significantly reduced the NHase activity. The absolute configuration of α-.-heterocyclic ethyl- and phenylacetamides, some of which were new compounds, was determined using electronic circular dichroism (ECD) spectroscopy. Additionally, their potential as cholinesterase’s inhibitors was evaluated. 2022 artículo científico 0100-4670 https://www.redalyc.org/articulo.oa?id=42970797002 https://www.redalyc.org/journal/429/42970797002/ https://www.redalyc.org/journal/429/42970797002/html/ https://www.redalyc.org/journal/429/42970797002/42970797002.epub https://www.redalyc.org/journal/429/42970797002/movil https://doi.org/10.26850/1678-4618eqj.v47.2.2022.p17-35 en http://www.redalyc.org/revista.oa?id=429 Eclética Química application/pdf Universidade Estadual Paulista Júlio de Mesquita Filho Eclética Química (Brasil) Num.2 Vol.47 |
| format | Artículo científico |
| id | redalyc_42970797002 |
| institution | Redalyc |
| language | en |
| publishDate | 2022 |
| publisher | Universidade Estadual Paulista Júlio de Mesquita Filho |
| spellingShingle | Levetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities Cintia Duarte de Freitas Milagre Química alkylation heterocycles biocatalysis electronic circular dichroism (ECD) Levetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities Cintia Duarte de Freitas Milagre Bruno Sergio do Amaral João Marcos Batista Junior Adriana Ferreira Lopes Vilela Carmen Lúcia Cardoso Humberto Marcio Santos Milagre Química alkylation heterocycles biocatalysis electronic circular dichroism (ECD) A chemoenzymatic approach for the synthesis of α-.-heterocyclic ethyl- and phenylacetamides, levetiracetam analogs, is described. Eight nitrile substrates were prepared through the .-alkylation of heterocycles (2-pyrrolidinone, 2-piperidinone, 2-oxopiperazine and 1-methylpiperazine) directly from hydroxyl group of ethyl and phenyl α-hydroxynitriles with yield of 35−71% after 12 h. Twenty nitrile hydratases (NHases) were screened and showed that the .-derivatives lactam substrates led to their correspondent amides by Co-type NHase with conversion and enantiomeric excess of up to 47.5 and 52.3% for (.)-enantiomer, while the piperazine substrates underwent spontaneous decomposition by retro-Strecker reaction. In order to avoid a retro-Strecker reaction of α-aminonitriles, ionic liquids and polyethylene glycol (PEG400) were evaluated as alternative green solvents to aqueous buffered solutions in different proportions. Temperature was another parameter investigated during reaction-medium engineering for process optimization. However, unconventional reaction media and low temperature significantly reduced the NHase activity. The absolute configuration of α-.-heterocyclic ethyl- and phenylacetamides, some of which were new compounds, was determined using electronic circular dichroism (ECD) spectroscopy. Additionally, their potential as cholinesterase’s inhibitors was evaluated. 2022 artículo científico 0100-4670 https://www.redalyc.org/articulo.oa?id=42970797002 https://www.redalyc.org/journal/429/42970797002/ https://www.redalyc.org/journal/429/42970797002/html/ https://www.redalyc.org/journal/429/42970797002/42970797002.epub https://www.redalyc.org/journal/429/42970797002/movil https://doi.org/10.26850/1678-4618eqj.v47.2.2022.p17-35 en http://www.redalyc.org/revista.oa?id=429 Eclética Química application/pdf Universidade Estadual Paulista Júlio de Mesquita Filho Eclética Química (Brasil) Num.2 Vol.47 |
| title | Levetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities |
| topic | Química alkylation heterocycles biocatalysis electronic circular dichroism (ECD) |
| url | https://www.redalyc.org/articulo.oa?id=42970797002 https://www.redalyc.org/journal/429/42970797002/ https://www.redalyc.org/journal/429/42970797002/html/ https://www.redalyc.org/journal/429/42970797002/42970797002.epub https://www.redalyc.org/journal/429/42970797002/movil https://doi.org/10.26850/1678-4618eqj.v47.2.2022.p17-35 |