N -Functionalization of β-aminophosphonates: cytotoxic effects of the new derivatives.

β-Aminophosphonates obtained by the Michael addition of primary amines to the double bond of diethyl vinylphosphonate proved to be suitable starting materials (amine components) in the Kabachnik-Fields reaction with formaldehyde and dialkyl phosphites or secondary phosphine oxides to afford N -phosphonylmethyl- and N -phosphinoylmethyl-β-aminophosphonates. On the other hand, the starting aminophosphonates were modified by N -acylation using acid chlorides. The N -acyl products were found to exist in a dynamic equilibrium of two conformers as suggested by the broad NMR signals. At 26 °C, there may be rotation around the N-C axis of the acylamide function. At the same time, low-temperature NMR measurements at -5 °C revealed the presence of two distinct rotamers that could be characterized by 31 P, 13 C and 1 H NMR data. The modified β-aminophosphonic derivatives were subjected to a comparative structure-activity analysis on MDA-MB-231, PC-3, A431 and Ebc-1 tumor cell lines, and in a few cases, significant activity was detected.