SYNTHESIS AND EVALUATION OF THE IN-VIVO TOLERANCE OF AMIDO FLUOROCARBON/FLUOROCARBON AND FLUOROCARBON/HYDROCARBON DOUBLE-CHAIN PHOSPHOCHOLINES DERIVING FROM DIAMINOPROPANOLS AND SERINE

The syntheses of various fluorocarbon/fluorocarbon and fluorocarbon/hydrocarbon amido-connected phosphocholines derived from diaminopropanols and serine are described. They were best obtained by phosphorylation of suitable alcohol precursors using 2-chloro-2-oxo-1,3,2-dioxaphospholane and subsequent ring opening with trimethylamine. The di-alkylamidopropanols were prepared by acylation,using perfluoroalkylated acid chlorides, of 1,3-diamino-2-propanol or of 2,3-diamino-1-propionic methylester followed by reduction of the ester bond. The perfluoroalkylated N-alkanoyl-serine alkylamides were prepared by condensation of Boc-O-Bn-L-serine with an aliphatic or perfluoroalkylated amine, Boc-deprotection, acylation and then hydrogenolysis for benzyl-deprotection. Acute toxicity evaluations indicate a very promising in vivo tolerance for these series of amido-linked compounds.