Reactivite du Bis(dichlorophosphoryl)imide Vis a Vis de La N,N-Bis(2-chloroéthyl)-amine Application a la Synthese de Molecules Susceptibles de Presenter une Activite Antitumorale

Abstract

The reaction of bis(dichlorophosphoryl)imide HN(P(O)Cl 2 ) 2 1 , with N,N-bis(2-chloroethyl)amine HN(CH 2 CH 2 Cl) 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 ( 31 P, 13 C) 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(CH 2 CH 2 Cl) 2 and ammonia on the one hand, HN(CH 2 CH 2 Cl) 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.

Keywords:

• Antitumoral Activity
• Bis(dichlorophosphoryl)imide
• Nmr
• N,N-bis(2-chloroethyl)-amine
• Reactivity