Synthesis and Cytotoxicity Evaluation of Novel Phosphonamidate and Aminophosphonates Containing Sterically Hindered Phenol and Terminal Propargyl Fragments

This study describes synthesis and biological evaluation of a new phosphonamidate and a series of α-aminophosphonates, employing propargylamine as a key NH-nucleophilic synthon. Two synthetic approaches were successfully implemented: (i) the reaction with O-ethyl (3,5-di-tert-butyl-4-hydroxybenzyl)phosphonоchloridate to form a P–N bond; (ii) a 1,6-aza-Michael addition to dialkyl/diphenyl [(3,5-di-tert-butyl-4-oxocyclohexa-2,5-dien-1-ylidene)methyl]phosphonate, affording the α-aminophosphonate scaffold via C–N bond formation. Initial in vitro cytotoxicity screening against a panel of human cancer cell lines using the MTT assay revealed that the phosphonamidate derivative exhibited the highest activity within the synthesized series.