Synthesis and conformational analysis of seco C-nucleosides and their diseco double-headed analogues of the 1,2,4-triazole, 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole

Reaction of D-glucono- (1) or D-galactono- (2) 1,5-lactones and D-glycero-D-guloheptonic-1,4-lactone (11) with thiocarbohydrazide (3) afforded the seco C-nucleosides 4-amino-3-(D-gluco- (4) or D-galacto- (5) pentitol-1-yl)-5-mercapto-1,2,4-triazoles and 4-amino-3-(D-glycero-D-gulo-hexitol-1-yl)-5-mercapto-1,2,4-triazole (12). Their conversions to the 3-(1,2,3,4,5-penta-O-acyl-D-gluco- (7 and 9) or the D-galacto (8 and 10) pentitol-1-yl)-6-substituted 1,2,4-triazolo[3,4-b]1,3,4-thiadiazole and 3-(1,2,3,4,5,6-hexa-O-acetyl-D-glycero-D-gulohexitol-1-yl)-6-methyl-1,2,4-triazolo[3,4-b]1,3,4-thiadiazole (13) were achieved under acylative conditions. Reaction of diethyl galactrate (17) with 3 gave 1,4-bis (4-amino-5-mercapto-1,2,4-triazol-3-yl)-galacto-tetritol (18), which upon reaction with acetic anhydride gave 1,4-bis(6-methyl-1,2,4-triazolo[3,4-b]1,3,4-thiadiazol-3-yl)-1,2,3,4-tetra-O-acetyl-galacto-tetritol (19). When the tetra-O-acetylgalactaric acid (15) was used instead of 17, the attack of 3 had taken place on the ester group rather than the carboxylic group, whereby 16 was obtained rather than the tetra-O-acetyl derivative of 18. The structures were confirmed by using H-1, C-13 and 2D NMR spectra (DQFCOSY and HMQC) experiments. The vicinal coupling constants were used to deduce the favored conformations. (C) 1998 Elsevier Science Ltd. All rights reserved.