Chemo-enzymatic flow synthesis of nature-inspired phenolic carbonates and carbamates as antiradical and antimicrobial agents

Abstract

A series of carbonate and carbamate derivatives of natural phenols, tyrosol and hydroxytyrosol, were synthetized through a novel chemo-enzymatic flow approach. First, the chemoselective synthesis of tyrosol and hydroxytyrosol carbonates was performed using immobilized lipase B from Candida antarctica as catalyst in tert-amyl alcohol, a non-conventional green solvent. Then, two selected carbonates were reacted in flow with the appropriate amine to obtain the desired carbamates. All the compounds were isolated in moderate to good yields. The carbonate and carbamate derivatives showed increased lipophilicity compared to the natural parental compounds, while maintaining similar radical scavenger properties. Moreover, their antimicrobial activity against four selected bacterial strains was evaluated and they showed improved activity in comparison with tyrosol and hydroxytyrosol.