78386-02-4Relevant articles and documents
Glucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approaches
Docampo-Palacios, Maite L.,Alvarez-Hernández, Anislay,Adiji, Olubu,Gamiotea-Turro, Daylin,Valerino-Diaz, Alexander B.,Viegas, Luís P.,Ndukwe, Ikenna E.,De Fátima, ?ngelo,Heiss, Christian,Azadi, Parastoo,Pasinetti, Giulio M.,Dixon, Richard A.
, p. 14790 - 14807 (2020/12/23)
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.
