NEW ANIONIC GLYCOPHOSPHOLIPIDS WITH 2 PERFLUOROCARBON OR 2 HYDROCARBON OR MIXED HYDROPHOBIC CHAINS

Novel amphiphilic anionic sugar phosphates esterified by various hydro phobic double-chain tails were synthesized. They differ primarily by t he design of their hydrophobic tail. Amphiphile 12a derives from phosp hogalactose and has two perfluoroalkylated hydrophobic chains; 12b has a pentenyloxy spacer between the mixed hydrocarbon/fludrocarbon doubl e-chain and the same head group; 12c and 14c are galactose and glucose derivatives with two hydrocarbon tail chains. All were prepared throu gh a three-step H-phosphonate route: reaction of the hydrophobic doubl e-chain alcohol on phosphorus trichloride (27-60%), followed by the ad dition of the appropriately protected sugar, by oxidation (50-81%), an d finally by deprotection of the sugar (58-95%). The starting alcohols were prepared through conventional reactions. Their synthesis was how ever, 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 nu mber of fluorinated chains or by increasing the total length, hence th e hydrophobicity of the amphiphile. Acute toxicity tests indicate maxi mum intravenously tolerated doses in mice of ca. 500 mg/kg body weight for 12a and 12b.