Exploring the Biological Potential of Hydroxytyrosol and Derivatives: Synthetic Strategies and Evaluation of Antiproliferative, Antioxidant, and Antimicrobial Activities

Phenolic compounds found in Extra Virgin Olive Oil (EVOO) have been associated with various health benefits. Bioavailability studies indicate that the phase I and II metabolites of these phenolic compounds can be detected in human urine and plasma following EVOO consumption. To contribute to the understanding of the biological potential of these phenolic compounds and their metabolites, this study delves into the synthesis, stability, and biological activities of hydroxytyrosol (HT), tyrosol (Tyr), and homovanillic alcohol (HVA), as well as their glucuronide, sulfate, and acetylated metabolites. For the first time, an effective synthesis was developed to allow the selective obtention of 3′- and 4′-glucuronides, as well as sulfates of HT. HT and its acetylated derivative emerged as the most potent compounds across antioxidant assessments, antiproliferative studies against human colorectal adenocarcinoma cell lines, and antimicrobial assays.