Total Synthesis of Urolithin M7 3-Glucuronide via Pd-Mediated Intramolecular Biaryl Coupling and Schmidt Glycosylation

Urolithin M7 is a gut microbial metabolite of ellagic acid, but its glucuronide conjugate has not been well characterized. We report the first total synthesis of urolithin M7 3-glucuronide through a convergent route that combines Pd-mediated intramolecular biaryl coupling with Schmidt glycosylation. Cyclization of phenyl benzoate 9 gave regioisomers 10a and 10b in 87% combined yield, with the desired 3-benzyloxy isomer formed preferentially in a 2:1 ratio. Selective protecting-group manipulation of 10a gave the glycosylation precursor, which underwent Schmidt glycosylation with a glucuronyl trichloroacetimidate donor to afford the protected β-glucuronide in 90% yield. Deprotection then furnished urolithin M7 3-glucuronide. The synthesis provides structurally defined urolithin M7 3-glucuronide for future analytical, metabolic, pharmacokinetic and biological studies.