Open AccessGlucuronidation of Methylated Quercetin Derivatives: Chemical and Biochemical Approaches
Author(s) -
Maite Docampo-Palacios,
Anislay Alvarez-Hernández,
Olubu A Adiji,
Daylín Gamiotea Turro,
Alexander B. Valerino-Díaz,
Luís P. Viegas,
Ikenna E. Ndukwe,
Ângelo de Fátima,
Christian Heiß,
Parastoo Azadi,
Giulio Maria Pasinetti,
Richard A. Dixon
Publication year - 2020
Publication title -
journal of agricultural and food chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.203
H-Index - 297
eISSN - 1520-5118
pISSN - 0021-8561
DOI - 10.1021/acs.jafc.0c04500
Subject(s) - glucuronidation , chemistry , quercetin , biochemistry , organic chemistry , microsome , enzyme , antioxidant
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.