Organofluorine compounds and fluorinating agents, Part 26: New reversed nucleosides — perfluoroalkyl substituted 1,2,3-triazoles linked to d-galactose and d-altrose

Reversed nucleosides, i.e., fluoroalkyl-substituted 1,2,3-triazoles linked to the C-atom 6 of d-galactose and d-altrose were synthesised by 1,3-dipolar cycloadditions using the monosaccharide azides 8, 11 and the perfluoroalkyl substituted phenyl vinyl sulfones 5–7. The starting material 11, methyl 6-azido-3,4-O-(trichloroethylidene)-2-O-cyclohexylcarbamoyl-6-deoxy-α-d-altropyranoside, was synthesized from methyl 2-O-cyclohexylcarbamoyl-3,4-O-(2,2,2-trichloroethylidene)-α-d-altropyranoside (9), via its 6-iododeoxy derivative 10. The homologous dipolarophiles 5–7, (E)-1-perfluoroalkyl-2-phenylsulfonyl-ethenes with a CF3 (5), n-C4F9 (6), and n-C6F13 (7) group, respectively, were obtained by Wittig–Horner olefination from phosphonate 4 and the corresponding perfluoroalkanals 1–3. Cycloaddition of 6-azido-6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactose (8) with the dipolarophiles 5–7 yielded the reversed nucleosides 12–14; altrose azide 11 gave the reversed nucleosides 15 and 16. The products of cycloaddition were deprotected using usual techniques. Thus, the 1-(6-deoxy-1,2:3,4-di-O-isopropylidene-α-d-galactopyranoso-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 13 and 14 were deacetalated by treatment with aqueous trifluoroacetic acid yielding the corresponding 1-(6-deoxy-α-d-galactopyranoso-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 17 and 18. The deprotection of the 1-[methyl 2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-α-d-altropyranosido-6-yl]-4-perfluoroalkyl-1,2,3-triazoles 15 and 16 was made stepwise (hydrodechlorination→deacetalation→decarbamoylation), i.e., the 1-(methyl 6-deoxy-d-altropyranosido-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 23 and 24 were synthesised via the ethylidene acetals 19, 20 and the 1-(methyl 2-O-cyclohexylcarbamoyl-6-deoxy-α-d-altropyranosido-6-yl)-4-perfluoroalkyl-1,2,3-triazoles 21 and 22. For the methyl 6-azido-2-O-cyclohexylcarbamoyl-6-deoxy-3,4-O-(2,2,2-trichloroethylidene)-α-d-altropyranoside (11) an X-ray structure is given.