Synthesis of iso-C-nucleoside analogues from 1-(methyl 2-O-benzyl-4,6-O- benzylidene-3-deoxy-α-D-altropyranosid-3-yl)but-3-yn-2-ones

Abstract

1-(Methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy-α-D-altropyranosid-3- yl)but-3-yn-2-one (3a) reacted with 3-amino-1H-1,2,4-triazole and 5-aminopyrazole-4-carboxylic acid derivatives in the presence of base to furnish the triazolo[1,5-a]pyrimidine (5) and the pyrazolo[1,5-a]pyrimidines (8a-d), respectively. Treatment of 1-(methyl 2-O-benzyl-4,6-O-benzylidene-3-deoxy- α-D-altropyranosid-3-yl)-4-phenyl-but-3-yn-2-one (3b) with cyanacetamide, 2-cyano-N-(4-methoxyphenyl)acetamide und N-aryl-3-oxo-butyramides afforded the substituted nicotinonitriles (11a-d). Furthermore, reaction of 3b with 2-benzimidazolyl-acetonitrile yielded the benz[4,5]imidazo[1,2-a]pyridine-4- carbonitrile (13). Deprotection of 8d in two steps afforded the 2-amino-N-benzyl-5-(methyl 3-deoxy-α-D-altropyranosid-3-yl-methyl) pyrazolo[1,5-a]pyrimidine-3-carboxamide (10). Compounds 5 and 11d were treated with AcOH/H2O to furnish the 5-(methyl 2-O-benzyl-3-deoxy-α-D- altropyranosid-3-yl-methyl)[1,2,4]triazolo[1,5-a]pyrimidine (6) and the 3-acetyl-1,2-dihydro-1-(4-methoxyphenyl)-6-(methyl 2-O-benzyl-3-deoxy-α-D- altropyranosid-3-yl-methyl)-4-phenylpyridin-2-one (12), respectively.