Total Synthesis of Urolithin C 3-Glucuronide

Urolithin is a metabolite of a class of compounds known as polyphenols which are found in various fruits, including pomegranates, nuts and strawberries.Urolithin is a biologically-active compound which has anti-inflammatory, antioxidant and anticancer properties.Our laboratory has focused on the use of a palladium-catalyzed intramolecular biaryl coupling reaction to yield urolithin C 3-glucuronide (uro-C 3-glur).The total synthesis of uro-C 3-glur has been accomplished in 11 steps starting from the commercially available 3,4-dimethoxybenzaldehyde. We now report full details of the total synthesis of urolithin C 3-glucuronide (1).Over recent years, it has been reported that gastrointestinal microbiota metabolize xenobiotics, which are produced from natural products, 1 i.e., urolithins, which are hydroxylated dibenzo [b,d]pyran-6-one derivatives, contain urolithin A (uro-A), urolithin B (uro-B), urolithin C (uro-C) and urolithin D (uro-D) derivatives which are produced in vivo by the gastrointestinal microbiota of humans and different animals upon intaking ellagitannins (ETs), which are high molecular weight polyphenols and ellagic acids (EAs) 2-7 (Figure).There are many different phenolic antioxidants, such as ETs and EAs, in walnuts and pomegranates, which have been linked to potential preventive effects against chronic diseases like Figure.Structures of urolithins A-D