The Modification of α-Aminophosphonates by Diastereoselective N-Alkenylation

Abstract 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, upon stirring the components without a catalyst at 26 °C for 24 h, or irradiating the mixture at 100 °C for 2 h, the addition of α-aminophosphonates to acetylenes, in this occasion, afforded diastereoselectively the Z isomer, as proven by NOESY/ROESY experiments. The effect of the new products was tested for cytotoxic activity on a myeloma cell line. It was found that these derivatives showed no antiproliferative effect on myeloma cells. Thus, there is a need for additional investigations to explore their antiproliferative properties and their effects on tumor cell viability.