Fluorinated acyclo-C-nucleoside analogues from glycals in two steps.
A convenient two-step strategy is reported for the synthesis of fluorinated optically pure acyclo-C-nucleoside analogues starting from simple glycals. In the first step, benzyl- or p-methoxybenzyl-protected glycals are treated with trifluoroacetic anhydride, bromodifluoroacetyl chloride, trichloroacetyl chloride, and perfluorooctanoyl chloride, respectively, in the presence of Et3N. This one-pot procedure yields 1,2-unsaturated sugars (1,5-anhydro-3,4,6-tri-O-benzyl (or p-methoxybenzyl) 2-deoxy-2-perhalogenoacyl-D-arabino / lyxo-hex-1-enitols 4-9) acylated at C-2. In the second step, a selective ring transformation is induced by treatment of the C-acylated glycals with bis-nucleophiles (hydrazine, phenylhydrazine, o-phenylenediamine, hydroxylamine). In particular, 1,5-anhydro-3,4,6-tri-O-benzyl-2-deoxy-2-trifluoroacetyl-D-arabino-hex-1-enitol (4) and 1,5-anhydro-2-deoxy-2-trifluoroacetyl-3,4,6-tri-O-(p-methoxybenzyl)-D-arabino-hex-1-enitol (8) were reacted with these nucleophiles generating the final C-nucleoside analogues of pyrazole (10, 11, and 12), diazepine (13), and isoxazole (15), respectively, containing a carbohydrate side chain linked to the heterocyclic ring.
Mamat
Constantin
C
Institut für Chemie, Universität Rostock, Albert-Einstein-Strasse 3a, D-18059 Rostock, Germany.
Hein
Martin
M
Miethchen
Ralf
R
D000215:Acylation; D000447:Aldehydes / Q000737:chemistry*; D005617:Chlorofluorocarbons, Methane / Q000737:chemistry; D009705:Nucleosides / Q000138:chemical synthesis*
D000447:Aldehydes; D005617:Chlorofluorocarbons, Methane; D009705:Nucleosides; C009554:fluoroform