New anionic glycophospholipids with two perfluorocarbon or two hydrocarbon or mixed hydrophobic chains

Novel amphiphilic anionic sugar phosphates esterified by various hydrophobic double-chain tails were synthesized. They differ primarily by the design of their hydrophobic tail. Amphiphile 12a derives from phosphogalactose and has two perfluoroalkylated hydrophobic chains; 12b has a pentenyloxy spacer between the mixed hydrocarbon/fludrocarbon double-chain and the same head group; 12c and 14c are galactose and glucose derivatives with two hydrocarbon tail chains. All were prepared through a three-step H-phosphonate route: reaction of the hydrophobic double-chain alcohol on phosphorus trichloride (27-60%), followed by the addition of the appropriately protected sugar, by oxidation (50-81%), and finally by deprotection of the sugar (58-95%). The starting alcohols were prepared through conventional reactions. Their synthesis was however, difficult, essentially as a result of lesser reactivity, and of low solubility of some of the intermediates related to the presence of the bulky, strongly hydrophobic chains. Preliminary biocompatibility assays indicate a reduction in hemolytic activity by increasing the number of fluorinated chains or by increasing the total length, hence the hydrophobicity of the amphiphile. Acute toxicity tests indicate maximum intravenously tolerated doses in mice of ca. 500 mg/kg body weight for 12a and 12b.