Synthesis and Antimicrobial Evaluation of (+)-Neoisopulegol-Based Amino and Thiol Adducts

Abstract

A library of neoisopulegol-based amino and thiol adducts was developed from (+)-neoisopulegol, derived from commercially available (−)-isopulegol. Michael addition of different nucleophiles towards its highly active α,β-unsaturated γ-lactone motif was accomplished, resulting in diverse amino and thiol analogs in stereoselective reactions. Then, the lactone ring was opened, with NH3 and benzylamine furnishing primary amide and N-benzyl-substituted amide derivatives, respectively. The in vitro antimicrobial effect of prepared compounds was also explored. The results revealed that naphthylmethyl-substituted β-aminolactone, the most promising compound, displayed selective inhibition for the Gram-positive bacteria S. aureus with an MIC (minimum inhibitory concentration) value of 12.5 μM. A docking study was performed to interpret the obtained results.