Synthesis of double-tailed (perfluoroalkyl)alkyl phosphosugars: new components for drug-carrying and -targeting systems

Abstract

Double-tailed d-glycose 3- and 6-[sodium (perfluoroalkyl)alkyl phosphates] were synthesized via the hydrogen phosphonate approach. Stable double-tailed (perfluoroalkyl)alkyl hydrogenphosphonates, prepared from double-tailed (perfluoroalkyl)alkanols and PCl 3-imidazole, reacted with 1,2:3,4-di- O-isopropylidene-α- d-galactopyranose or with 1,2:5,6 -di- O-isopropylidene-α- d-glucofuranose in the presence of Me 3CCOCl as the condensing agent to give, after oxidation with aqueous iodine, the corresponding O-protected glycose phosphate diesters. O-Deisopropylidenation of the latter by aqueous trifluoroacetic acid afforded the target compound in 70% yield, based on the protected glycosides. Condensation of 1,2,3,4-tetra- O-acetyl-β- d-glucopyranose or -mannopyranose with double-tailed (perfluoroalkyl)alkyl hydrogenphosphonates or 10-eicosyl hydrogenphosphonate, via the coupling and oxidation steps described above, afforded per- O-acetylglycose phosphodiesters. O-Deacetylation with MeONa-MeOH was achieved in 65% yield based on the protected sugar. All the compounds were characterized by 19F, 1H, 13C, and 31P NMR data. Preliminary biocompatibility assays indicate a reduction of hemolytic activity when fluorinated chains are present and maximum tolerated doses of ca. 125 mg/kg body weight in mice.