A Novel Three-Step Synthesis of a Pyrrolopyrimidine C-Nucleoside

Article abstract of DOI:10.1021/jo00357a021

The phosphorus ylide, <(2,4-dimethoxy-5-nitropyrimidin-6-yl)methyl>triphenylphosphorane (10) was synthesized in two steps from 6-(bromomethyl)-2,4-dimethoxy-5-nitropyrimidine (8).Compound 10 was condensed with 2,3-O-isopropylidene-5-O-(triphenylmethyl)-D-ribofuranose (1) to form the anomeric pair of protected homo-C-nucleosides, 2,4-dimethoxy-5-nitro-6-C-<(2,3-O-isopropylidene-5-O-(triphenylmethyl)-β-D-ribofuranosyl)methyl>pyrimidine (11) and 2,4-dimethoxy-5-nitro-6-C-<(2,3-O-isopropylidene-5-O-(triphenylmethyl)-α-D-ribofuranosyl)methyl>pyrimidine (12).Compound 10 also reacted with 2,3-O-isopropylidene-D-ribofuranose (6) to form the nontritylated compounds 2,4-dimethoxy-6-C-<(2,3-O-isopropylidene-β- and -α-D-ribofuranosyl)methyl>-5-nitropyrimidines (14 and 15).Acid treatment of 11 or 12 afforded the deblocked homo-C-nucleoside 6-C-<(β-D-ribofuranosyl)methyl>-5-nitropyrimidine-2,4-dione (16), while reduction of 11 produced the 5-amino-pyrimidine homo-C-nucleoside 17 in quantitative yield. 6-(Cyanomethyl)-2,4-dimethoxy-5-nitropyrimidine (18) reacted with 2,3-O-isopropylidene-5-O-(triphenylmethyl)-D-ribofuranosyl chloride (19) to form the R and S diastereomers of 2-(2,4-dimethoxy-5-nitropyrimidin-6-yl)-2-(2,3-O-isopropylidene-5-O-(triphenylmethyl)-α-D-ribofuranosyl)acetonitrile (20a and 20b).The major component (20a) was reduced catalytically to the pyrrolo<3,2-d>pyrimidine 21.Under mild acid treatment 21 was deblocked to form 2,4-dimethoxy-7-C-(α-D-ribofuranosyl)pyrrolo<3,2-d>pyrimidine (22).Strong, aqueous acid treatment of 21 afforded a 1/1 mixture of 22 and the β anomer 23.