The Modification of α-Aminophosphonates by Diastereoselective N-Alkenylation

Two new families of α-aminophosphonates were prepared to widen the pool of these potentially biologically active species. α-Alkylamino- and α-amino-arylmethylphosphonates were added on the triple bond of dialkyl acetylenedicarboxylates to afford the corresponding N-alkenylated α-aminophosphonic derivatives. Performing the reactions of α-alkylamino-phosphonates at 26 °C in the presence of diazabicycloundecene (DBU) as the catalyst, the additions took place in a diastereoselective manner to afford one isomer that was the E-form according to NOESY and ROESY NMR measurements. In the absence of a catalyst, completion of the addition required a longer time. The similar reaction of α-aminophosphonates with an NH2 group, in the presence of DBU, led to a mixture of two diastereoisomers. However, stirring the components without a catalyst at 26 °C for 24 h, or irradiating the mixture at 100 °C for 2h, the addition of α-aminophosphonates to acetylenes was diastereoselective affording, this occasion, the Z isomer proved by NOESY/ROESY experiments. The effect of the new products was tested for cytotoxic actctivity on a myeloma cell line. It was found that these derivatives showed no antiproliferative effect on myeloma cells. Thus, there is need for additional investigations to explore their antiproliferative properties, and their effects on tumor cell viability.