Glucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approaches

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dc.contributor.authorDocampo-Palacios, Maite L.
dc.contributor.authorAlvarez-Hernández, Anislay
dc.contributor.authorAdiji, Olubu
dc.contributor.authorGamiotea-Turro, Daylin [UNESP]
dc.contributor.authorValerino-Diaz, Alexander B. [UNESP]
dc.contributor.authorViegas, Luís P.
dc.contributor.authorNdukwe, Ikenna E.
dc.contributor.authorDe Fátima, Ângelo
dc.contributor.authorHeiss, Christian
dc.contributor.authorAzadi, Parastoo
dc.contributor.authorPasinetti, Giulio M.
dc.contributor.authorDixon, Richard A.
dc.contributor.institutionUniversity of North Texas
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionUniversity of Coimbra
dc.contributor.institutionUniversity of Georgia
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.contributor.institutionThe Mount Sinai School of Medicine
dc.date.accessioned2021-06-25T10:18:20Z
dc.date.available2021-06-25T10:18:20Z
dc.date.issued2020-12-16
dc.description.abstractBotanical supplements derived from grapes are functional in animal model systems for the amelioration of neurological conditions, including cognitive impairment. Rats fed with grape extracts accumulate 3′-O-methyl-quercetin-3-O-β-d-glucuronide (3) in their brains, suggesting 3 as a potential therapeutic agent. To develop methods for the synthesis of 3 and the related 4′-O-methyl-quercetin-7-O-β-d-glucuronide (4), 3-O-methyl-quercetin-3′-O-β-d-glucuronide (5), and 4′-O-methyl-quercetin-3′-O-β-d-glucuronide (6), which are not found in the brain, we have evaluated both enzymatic semisynthesis and full chemical synthetic approaches. Biocatalysis by mammalian UDP-glucuronosyltransferases generated multiple glucuronidated products from 4′-O-methylquercetin, and is not cost-effective. Chemical synthetic methods, on the other hand, provided good results; 3, 5, and 6 were obtained in six steps at 12, 18, and 30% overall yield, respectively, while 4 was synthesized in five steps at 34% overall yield. A mechanistic study on the unexpected regioselectivity observed in the quercetin glucuronide synthetic steps is also presented.en
dc.description.affiliationBioDiscovery Institute Department of Biological Sciences University of North Texas
dc.description.affiliationChemistry Institute-Araraquara UNESP-São Paulo State University
dc.description.affiliationCoimbra Chemistry Center Chemistry Department University of Coimbra
dc.description.affiliationComplex Carbohydrate Research Center University of Georgia, 315 Riverbend Rd
dc.description.affiliationDepartment of Chemistry Federal University of Minas Gerais
dc.description.affiliationDepartment of Psychiatry The Mount Sinai School of Medicine
dc.description.affiliationUnespChemistry Institute-Araraquara UNESP-São Paulo State University
dc.format.extent14790-14807
dc.identifierhttp://dx.doi.org/10.1021/acs.jafc.0c04500
dc.identifier.citationJournal of Agricultural and Food Chemistry, v. 68, n. 50, p. 14790-14807, 2020.
dc.identifier.doi10.1021/acs.jafc.0c04500
dc.identifier.issn1520-5118
dc.identifier.issn0021-8561
dc.identifier.scopus2-s2.0-85097896308
dc.identifier.urihttp://hdl.handle.net/11449/205611
dc.language.isoeng
dc.relation.ispartofJournal of Agricultural and Food Chemistry
dc.sourceScopus
dc.subjectglucuronidation
dc.subjectglucuronosyltransferases
dc.subjectintrinsic reaction coordinate
dc.subjectmethoxylated quercetin
dc.subjectmolecular modelling
dc.subjectphase II metabolites
dc.subjectsemi-synthesis
dc.titleGlucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approachesen
dc.typeArtigo
unesp.author.orcid0000-0001-5205-3989[1]
unesp.author.orcid0000-0001-7600-8429[4]
unesp.author.orcid0000-0002-6368-3086[5]
unesp.author.orcid0000-0003-2312-990X[6]
unesp.author.orcid0000-0003-3010-695X 0000-0003-3010-695X[8]
unesp.author.orcid0000-0003-1118-8953[9]
unesp.author.orcid0000-0002-1524-5196[11]
unesp.author.orcid0000-0001-8393-9408[12]

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