Purines, pyrimidines, and imidazoles. Part XL. A new synthesis of a D-ribofuranosylamine derivative and its use in the synthesis of pyrimidine and imidazole nucleosides

Abstract

2,3-O-Isopropylidene-D-ribofuranosylamine has been prepared in high yield as the stable crystalline toluene-p-sulphonate by reaction of D-ribopyranosylamine with acetone, 2,2-dimethoxypropane, and toluene-p-sulphonic acid. The anomeric configuration of the furanosylamine in various solvents has been investigated by n.m.r. spectroscopy and optical rotation measurements. In chloroform the β-form predominates whereas in dimethyl sulphoxide a high proportion of the α-form is present. A bis(isopropylideneribofuranosyl)amine of unknown anomeric configuration has also been prepared from the furanosylamine toluene-p-sulphonate; this has also been obtained as a by-product in some reactions.

Reaction of the furanosylamine with several, α-cyano, -acetyl, or -ethoxycarbonyl-β-ethoxy-N-ethoxycarbonyl-acrylamides occurs in both aqueous and non-aqueous solutions to give corresponding 5-substituted uracil α- and β-ribofuranosides. Assignments of anomeric configurations were confirmed by n.m.r. spectroscopy, by comparison with known compounds, and, in the case of 5-ethoxycarbonyluridine, by hydrolysis to the uridine-5-carboxylic acid and smooth decarboxylation of this to uridine by a new method which has also been used to decarboxylate uracil-5-carboxylic acid and its 1-methyl and 1-phenyl derivatives.

The furanosylamine with β-methoxy-α-methylacryloyl isothiocyanate also gave, via an intermediate acyclic thiourea riboside, 2-thiothymine 1-(isopropylidene-β-D-ribofuranoside).

Treatment of the furanosylamine either with ethyl N-[alkoxycarbonyl or carbamoyl(cyano)methyl]formimidates, or with ethylformimidate hydrochloride [to give a mixture of ethyl N-(2,3-O-isopropylidene-α- and β-ribofuranosyl)-formimidates], followed by ethyl α-amino(cyano)acetate, gave 5-amino-4-(alkoxycarbonyl or carbamoyl)imidazole isopropylidene-α- and β-ribofuranosides, from which the isopropylidene groups may be removed by aqueous acetic acid. Phosphorylation of the two anomeric esters gave corresponding 5-aminoimidazole-4-carboxylic acid α- and β-ribotides.

Structures of the aminoimidazole nucleosides and nucleotides were confirmed by comparisons with known compounds and by use of spectral (especially c.d.) techniques. Rates of reaction of several formimidates and acetimidates with cyclohexylamine have been examined.