Synthesis of 4-aminobenzimidazole and 4-nitroindole nucleosides and nucleotides
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Abstract
The synthesis of two analogues of adenosine, 4-amino-1-β-D-ribofuranosylbenzimidazole and 4-nitro-1-β-D-ribofuranosylindole,
and their associated nucleoside-5' phosphates
is described. The interaction of 4-arninobenzimidazole
nucleoside-5' triphosphate with the enzyme adenylate kinase is also described.
4-Nitro-l-β-D-ribofuranosylbenzimidazole was prepared from 4(7)-nitrobenzimidazole and 2,3,5-tri-0-benzoyl-ribofuranosyl bromide by the mercuric cyanide method in 50-60%
yield. After removal of the benzoyl groups, 4-aminobenzimidazole nucleoside-5' phosphate was prepared by direct phosphorylation followed by reduction of the nitro group by hydrogenation over 5% Pd/C in 60% yield. The nucleoside
di- and triphosphates were prepared using the anion exchange method of Michelson.
4-Nitro-1-β-D-ribofuranosylindole was synthesized in 70﹪yield by condensing 4-nitroindole and 2,3,5-tri-O-benzoylriboruranosyl bromide in the presence of silver (𝙸) oxide in benzene. The benzoyl groups were removed with methanolic ammonia. The nucleoside-5' phosphate was prepared
by blocking the 2' and 3' hydroxyl, groups with the ethoxyformylidene group and condensing the 5' hydroxyl with cyanoethyl phosphate in the presence of mesitylene sulfonyl chloride. The nucleoside-5' diphosphate was prepared by the anion exchange method. An unsuccessful attempt to
prerared the nucleoside triphosphate by the same method is described.
Kinetic measurements were made for the interaction of 4-aminobenzirnidazole nucleoside-5' triphosphate with adenylate kinase in the presence of 1 mM adenosine monophosphate.
Km for the benzimidazole nucleotide is 0.40 mM
as opposed to 0.029 mM for a.denosine triphosphate under the same conditions. Vmax for the benzimidazole triphosphate is 12 times that of ATP.
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