Glucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approaches
| Autor: | Daylin Gamiotea-Turro, Anislay Alvarez-Hernandez, Christian Heiss, Alexander B. Valerino-Díaz, Richard A. Dixon, Luís P. Viegas, Giulio Maria Pasinetti, Parastoo Azadi, Ângelo de Fátima, Olubu A Adiji, Ikenna E. Ndukwe, Maite L Docampo-Palacios |
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| Přispěvatelé: | University of North Texas, Universidade Estadual Paulista (Unesp), University of Coimbra, University of Georgia, Universidade Federal de Minas Gerais (UFMG), The Mount Sinai School of Medicine |
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Male Glucuronidation 01 natural sciences semi-synthesis Article chemistry.chemical_compound Glucuronides Animals heterocyclic compounds Vitis Glucuronosyltransferase phase II metabolites chemistry.chemical_classification glucuronosyltransferases intrinsic reaction coordinate Molecular Structure 010401 analytical chemistry glucuronidation Regioselectivity Brain General Chemistry Semisynthesis 0104 chemical sciences molecular modelling Rats Enzyme chemistry Biochemistry Biocatalysis Yield (chemistry) methoxylated quercetin Quercetin General Agricultural and Biological Sciences Glucuronide 010606 plant biology & botany |
| Zdroj: | J Agric Food Chem Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1520-5118 |
| Popis: | Made available in DSpace on 2021-06-25T10:18:20Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-12-16 Botanical 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. BioDiscovery Institute Department of Biological Sciences University of North Texas Chemistry Institute-Araraquara UNESP-São Paulo State University Coimbra Chemistry Center Chemistry Department University of Coimbra Complex Carbohydrate Research Center University of Georgia, 315 Riverbend Rd Department of Chemistry Federal University of Minas Gerais Department of Psychiatry The Mount Sinai School of Medicine Chemistry Institute-Araraquara UNESP-São Paulo State University |
| Databáze: | OpenAIRE |
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