Synthesis of 1,3,4-Thiadiazole and 1,2,4-Triazole acyclo C-Nucleosides

Abstract

Abstract Reaction of 4-arylthiosemicarbazides (1) with 2,3,4,5-tetra-O-acetylgalactaroyl dichloride (2) gave the corresponding 2,3,4,5-tetra-O-acetylgalactaroyl-bis(4-aryl-thiosemicarbazides (3). The latter compounds underwent dehydrative cyclization by heating with phosphoryl chloride to give 1,2,3,4-tetra-O-acetyl-1,4-bis(5-arylamino-1,3,4-thiadiazol-2-yl)galacto-tetritols (4) which afforded, upon de-O-acetylation with methanolic ammonia, the corresponding 1,4-bis(5-arylamino-1,3,4-thiadiazol-2-yl)-galacto-tetritols (5). Compounds 3 were also cyclodehydrated, in a different way, with concomitant de-O-acetylation upon treatment with ethanolic sodium ethoxide to give 1,4-bis(4-aryl-5-thioxo-1,2,4-triazol-3-yl)galacto-tetritols (6). Acetylation of 6 with acetic anhydride in the presence of pyridine afforded 1,2,3,4-tetra-O-acetyl-1,4-bis(1-acetyl-4-aryl-5-thioxo-1,2,4-triazol-3yl)galacto-tetritols (7). Compounds 3a, 3b and 6a-c showed no antibacterial activity against Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, or Staphylococcus aureus and showed weak to moderate antifungal activity against Aspergillus terreus and Candida albicans.