Synthesis of 2-fluoro and 4-fluoro galactopyranosyl phosphonate analogues of UDP-Gal.

Two novel nonisosteric UDP-Gal analogues, (2-deoxy-2-fluoro- and 4-deoxy-4-fluoro-α-D-galactopyranosyl) phosphonoyl phosphates, were synthesized by optimized multistep procedures starting from 3,4,6-tri-O-benzyl-D-galactal and allyl 2,3,6-tri-O-benzyl-α-D-glucopyranoside, respectively. The key steps were a Michaelis-Arbuzov reaction of respective deoxy-fluoro-D-galactopyranosyl acetate with triethyl phosphite followed by a Moffatt-Khorana coupling reaction with UMP-morpholidate. The structure of all new compounds was confirmed by NMR and mass spectroscopies..

Perfluoroalkylated derivatives of 6-deoxy-6-ethylamino-D-galactose, 1-deoxy-1-methylamino-D-glucitol, and 1-amino-1-deoxy-D-glucitol: syntheses, hemocompatibility, and effect on perfluorocarbon emulsion.

N-polyfluoroalkyl derivatives of 6-deoxy-6-ethylamino-1,2;3,4-di-O-isopropylidene-alpha-D-galactopyranose (8-10), 1-deoxy-1-methylamino-D-glucitol (13-15), and 1-amino-1-deoxy-D-glucitol (16-18), all possessing perfluoroalkyl segment, were prepared using nucleophilic epoxide ring opening of 2-[(perfluoroalkyl)methyl]oxiranes 1-3. Co-emulsifying properties and hemolytic activity of the new perfluoroalkylated amphiphiles were tested. Both types of the polyol derivatives 8-10 and 13-18 generally displayed good to excellent co-emulsifying properties on testing on perfluorodecalin/Pluronic F-68 microemulsions. Mono-perfluoroalkylated compounds 8-10 and 13-15 displayed high hemolysis, whereas acyclic bis-perfluoroalkylated compounds 16-18 were non-hemolytic even for short perfluorobutyl segment (16). The properties were generally improving with increasing perfluoroalkyl chain length.

A concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and 2-acetamido-2-deoxy-D-mannopyranosides.

4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-alpha- and beta-D-mannopyranosides were prepared from methyl 4,6-O-benzylidene-alpha-D-glucopyranoside and 1,3,4,6-tetra-O-acetyl-alpha-D-glucopyranose, respectively. Chemoselective reduction of both azides with hydrogen sulfide readily afforded 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-alpha-D- and -beta-D-mannopyranosides in higher yields than reduction with triphenylphosphine or a polymer-supported triarylphosphine. Subsequent de-O-acetylation yielded 4-nitrophenyl 2-acetamido-2-deoxy-alpha-D-mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-beta-D-mannopyranoside in 20% and 44% overall yields, respectively.

Novel perfluoroalkylated derivatives of D-galactopyranose and xylitol for biomedical uses. Hemocompatibility and effect on perfluorocarbon emulsions.

6-O-(4,4,5,5,6,6,7,7,7-Nonafluoro-2-hydroxyheptyl)-, 6-O-(4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoro-2-hydroxynonyl)-, and 6-O-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-2-hydroxyundecyl)-d-galactopyranose (9, 10, and 11, resp.) were prepared by a two-step synthesis including the reaction of 1,2:3,4-di-O-isopropylidene-alpha-d-galactopyranose with 2-[(perfluoroalkyl)methyl]oxiranes under catalysis with BF(3).Et(2)O. Similarly, 1-O-(4,4,5,5,6,6,7,7,7-nonafluoro-2-hydroxyheptyl)-, 1-O-(4,4,5,5,6,6,7,7,8,8,9,9,9-tridecafluoro-2-hydroxynonyl)-, 1-O-(4,4,5,5,6,6,7,7,8,8,9,9,10,10,11,11,11-heptadecafluoro-2-hydroxyundecyl)-dl-xylitol (18, 19, and 20, resp.) were prepared by a two-step synthesis from the corresponding 1,2:3,4-di-O-isopropylidene-dl-xylitol. Most of the both types of fluoroalkylated carbohydrate derivatives 9-11 and 18-20 generally displayed very low level of hemolytic activity and excellent co-emulsifying properties on testing on perfluorodecalin-Pluronic F-68 microemulsions.

Novel amphiphilic fluoroalkylated derivatives of xylitol, D-glucose and D-galactose for medical applications: hemocompatibility and co-emulsifying properties.

1-O-(4,4,5,5,6,6,7,7,8,8,9,9,9-Tridecafluorononyl)xylitol 6 was synthesized as a novel standard compound for the assessment of hemocompatibility and co-emulsifying properties in microemulsions for biomedical uses. 3-O-(1,1,2,4,4,5,7,7,8,8,9,9,9-Tridecafluoro-5-trifluoro-methyl-3,6-dioxanonyl)-D-glucose 9 and 6-O-(1,1,2,4,4,5,7,7,8,8,9,9,9-tridecafluoro-5-trifluoromethyl-3,6-dioxanonyl)-D-galactose 12 were synthesized by nucleophilic addition of protected carbohydrates to perfluorinated vinyl oligoether. Biological tests revealed very good hemocompatibility and co-emulsifying properties for the amphiphiles 6, 9 and 12.