Gorecka, A, Schacht, H, Fraser, MK, Teriosina, A, London, JA, Barsukov, IL, Powell, AK, Cartmell, A, Stachulski, AV and Yates, EA (2024) Synthetic β-d-Glucuronides: Substrates for Exploring Glucuronide Degradation by Human Gut Bacteria. ACS Omega, 10 (1). pp. 1419-1428. ISSN 2470-1343

Preview

Text Synthetic βDGlucuronides Substrates for Exploring GlucuronideDegradation by Human Gut Bacteria.pdf - Published Version Available under License Creative Commons Attribution. Download (4MB) | Preview

Abstract

The human gut microbiota (HGM) is a complex ecosystem subtly dependent on the interplay between hundreds of bacterial species and numerous metabolites. Dietary phenols, whether ingested (e.g., plant-derived guaiacol, mequinol, or resveratrol) or products of bacterial fermentation (e.g., p-cresol), have been attributed with influencing bacterial growth and host health. They are cleared by phase II metabolism, one form utilizing β-d-glucuronidation, but encounter bacterially derived glucuronidases capable of hydrolyzing them to release their phenolic and glucuronic acid moieties with potential effects on host cells or the surrounding bacterial population. Tools to enable the detailed study of their activity are currently lacking. Syntheses of β-d-glucuronides from methyl 1,2,3,4 tetra-acetyl β-d-glucopyranosyluronate by direct glycosylation with 2-, 3-, or 4-methoxy- and 4-fluorophenol acceptors employing trimethylsilyl triflate catalysis are reported. Yields (methoxy series) were modest. An improved route from methyl 1,2,3,4-tetra-acetyl β-d-glucopyranosyluronate via selective anomeric deprotection (N-methyl piperazine) and conversion to an α-trichloroacetimidate glycosyl donor was employed. Coupling with 2- and 3-methoxyphenol acceptors and deprotection provided 2- and 3-methoxyphenyl β-d-glucuronides in 2-fold improved overall yield. These naturally occurring methoxyphenyl glucuronides augment available model substrates of dietary glucuronides, which include 3- and 4′-linked resveratrol. The use of model glucuronides as substrates was illustrated in studies of β-d-glucuronidase activity employing cell lysates of 9 species of HGM (Bacteroidetes), revealing distinct outcomes. Contrasting effects on bacterial growth were also observed between the free phenolic components, their respective glucuronides, and glucuronic acid. The glucuronide of 4-fluorophenol provided sensitive and background-free detection of β-glucuronidase activity using 19F NMR.

Item Type:	Article
Uncontrolled Keywords:	Nutrition; Complementary and Integrative Health; Dietary Supplements; 0904 Chemical Engineering; 0912 Materials Engineering
Subjects:	R Medicine > RS Pharmacy and materia medica
Divisions:	Pharmacy and Biomolecular Sciences
Publisher:	American Chemical Society (ACS)
SWORD Depositor:	A Symplectic
Date Deposited:	17 Jan 2025 14:09
Last Modified:	17 Jan 2025 14:15
DOI or ID number:	10.1021/acsomega.4c09036
URI:	https://researchonline.ljmu.ac.uk/id/eprint/25315

View Item