Efficient chemical synthesis of (epi)catechin glucuronides: brain-targeted metabolites for treatment of alzheimer's disease and other neurological disorders
Grape seed extract (GSE) is rich in flavonoids and has been recognized to possess human health benefits. Our group and others have demonstrated that GSE is able to attenuate the development of Alzheimer’s disease (AD). Moreover, our results have disclosed that the anti-Alzheimer’s benefits are not d...
| Autores: | , , , , , |
|---|---|
| Formato: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | Brasil |
| Recursos: | Universidade Federal de Minas Gerais (UFMG) |
| Repositorio: | Repositório Institucional da UFMG |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.ufmg.br:1843/77735 |
| Acesso em linha: | https://doi.org/10.1021/acsomega.0c04512 http://hdl.handle.net/1843/77735 https://orcid.org/0000-0001-5205-3989 https://orcid.org/0000-0002-9962-3456 https://orcid.org/0000-0003-2344-5590 http://orcid.org/0000-0001-9985-2980 https://orcid.org/0000-0002-1524-5196 https://orcid.org/0000-0001-8393-9408 |
| Access Level: | acceso abierto |
| Palavra-chave: | Catechin Glucuronides Catechin Epicatechin Glucuronides Epicatechin Alzheimer's disease Farmacologia Alzheimer, Doença de Uva Flavonóides Espectroscopia de ressonância nuclear |
| Resumo: | Grape seed extract (GSE) is rich in flavonoids and has been recognized to possess human health benefits. Our group and others have demonstrated that GSE is able to attenuate the development of Alzheimer’s disease (AD). Moreover, our results have disclosed that the anti-Alzheimer’s benefits are not directly/solely related to the dietary flavonoids themselves, but rather to their metabolites, particularly to the glucuronidated ones. To facilitate the understanding of regioisomer/stereoisomer-specific biological effects of (epi)catechin glucuronides, we here describe a concise chemical synthesis of authentic standards of catechin and epicatechin metabolites 3–12. The synthesis of glucuronides 9 and 12 is described here for the first time. The key reactions employed in the synthesis of the novel glucuronides 9 and 12 include the regioselective methylation of the 4′-hydroxyl group of (epi)catechin (≤1.0/99.0%; 3′-OMe/4′-OMe) and the regioselective deprotection of the tert-butyldimethylsilyl (TBS) group at position 5 (yielding up to 79%) over the others (3, 7 and 3′ or 4′). |
|---|