Reactivity of bis(dichlorophosphoryl)imide with N,N-bis(2-chloroethyl)amine - Application to the synthesis of molecules with potential antitumoral activity [French]

摘要

The reaction of bis(dichlorophosphoryl)imide HN(P(O)Cl-2)(2) 1, with N,N-bis(2-chloroethyl)amine HN(CH2CH2Cl)(2) (bCEA) has been studied in order to synthesize Phosphorus-Nitrogen derivatives which present anti-tumoral activity. It has been possible to show the formation of the mono 2, di 3 and tetrasubstituted 4 derivatives as well as the existence of diastereoisomers for 2 and 3. The combined use of NMR (P-31, C-13) and mass spectrometry has allowed us to show the instability of the tetrasubstituted derivative wich is transformed to the O-alkylated compound 4a with elimination of HCl. We studied also the cosubstitution reactions of 1 by HN(CH2CH2Cl)(2) and ammonia on the one hand, HN(CH2CH2Cl)(2) and glycine ethyl ester on the other hand. Spectroscopic studies of the resulting products revealed the involvement of N-alkylation reactions leading to 6 and 7. The study of the antitumoral activity of these compounds was undertaken. Only the phosphazene derivative 2 which contains a bifunctionnal alkylating agent exhibited a moderate anti-tumoral activity. [References: 18]