Hydroxytyrosol lipophilic analogues: Enzymatic synthesis, radical scavenging activity and DNA oxidative damage protection

The olive oil phenol hydroxytyrosol (3), as well its metabolite homovanillic alcohol (4), were subjected to chemoselective lipase-catalysed acylations, affording with good yield 10 derivatives (5–14) bearing C2, C3, C4, C10 and C18 acyl chains at C-1. Hydroxytyrosol (3) and its lipophilic derivatives showed very good DPPH radical scavenging activity. Compounds 3, 4 and their lipophilic analogues 5–14 were subjected to the atypical Comet test on whole blood cells: 3 and its analogues 5 and 6, with little hydrophobic character (log P ⩽ 1.20), showed a good protective effect against H2O2 induced oxidative DNA damage. The homovanillic alcohol 4 and its analogues 10–14 resulted scarcely effective both as radical scavengers and antioxidant agents.