Levetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities

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MetadadosDescriçãoIdioma
Autor(es): dc.contributorUniversidade Estadual Paulista (UNESP)-
Autor(es): dc.contributorUniversidade Federal de São Carlos (UFSCar)-
Autor(es): dc.contributorUniversidade de São Paulo (USP)-
Autor(es): dc.creatorde Freitas Milagre, Cintia Duarte-
Autor(es): dc.creatordo Amaral, Bruno Sergio-
Autor(es): dc.creatorJunior, João Marcos Batista-
Autor(es): dc.creatorVilela, Adriana Ferreira Lopes-
Autor(es): dc.creatorCardoso, Carmen Lúcia-
Autor(es): dc.creatorMilagre, Humberto Marcio Santos-
Data de aceite: dc.date.accessioned2025-08-21T21:29:33Z-
Data de disponibilização: dc.date.available2025-08-21T21:29:33Z-
Data de envio: dc.date.issued2023-03-02-
Data de envio: dc.date.issued2023-03-02-
Data de envio: dc.date.issued2021-12-31-
Fonte completa do material: dc.identifierhttp://dx.doi.org/10.26850/1678-4618eqj.v47.2.2022.p17-35-
Fonte completa do material: dc.identifierhttp://hdl.handle.net/11449/241862-
Fonte: dc.identifier.urihttp://educapes.capes.gov.br/handle/11449/241862-
Descrição: dc.descriptionA chemoenz matic a roach for the synthesis of α-N-heterocyclic ethyl- and phenylacetamides, levetiracetam analogs, is described. Eight nitrile substrates were prepared through the N-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 N-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 (S)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-N-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.(Figure presented)-
Descrição: dc.descriptionGlaxoSmithKline-
Descrição: dc.descriptionCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)-
Descrição: dc.descriptionFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)-
Descrição: dc.descriptionConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)-
Descrição: dc.descriptionSão Paulo State University Institute of Chemistry-
Descrição: dc.descriptionFederal University of São Carlos Department of Chemistry, São Carlos-
Descrição: dc.descriptionFederal University of São Paulo Institute of Science and Technology-
Descrição: dc.descriptionUniversity of São Paulo Faculty of Philosophy Sciences and Letters, Ribeirão Preto-
Descrição: dc.descriptionSão Paulo State University Institute of Chemistry-
Descrição: dc.descriptionCAPES: 001-
Descrição: dc.descriptionFAPESP: 2010/02305-5-
Descrição: dc.descriptionFAPESP: 2013/16636-1-
Descrição: dc.descriptionFAPESP: 2014/25222-9-
Descrição: dc.descriptionFAPESP: 2014/50249-8-
Descrição: dc.descriptionFAPESP: 2014/50926-0-
Descrição: dc.descriptionFAPESP: 2019/15230-8-
Descrição: dc.descriptionFAPESP: 2019/22319-5-
Descrição: dc.descriptionCNPq: 465637/2014-0-
Formato: dc.format17-35-
Idioma: dc.languageen-
Relação: dc.relationEcletica Quimica-
???dc.source???: dc.sourceScopus-
Palavras-chave: dc.subjectbiocatalysis-
Palavras-chave: dc.subjectelectronic circular dichroism (ECD)-
Palavras-chave: dc.subjectN-alkylation-
Palavras-chave: dc.subjectN-heterocycles-
Título: dc.titleLevetiracetam analogs: chemoenzymatic synthesis, absolute configuration assignment and evaluation of cholinesterase inhibitory activities-
Tipo de arquivo: dc.typelivro digital-
Aparece nas coleções:Repositório Institucional - Unesp

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