Phosphorylated imidazoles, formation

Many enzymes that mediate phosphoryl transfer from ATP are thought to do so via the formation of a phosphorylated imidazole residue of histidine (Scheme 49). Spontaneous reactions of amines with ATP are legendarily slow, but now a systematic study, involving trapping of the phosphorylated amine with F , has shown that amines (pyridines, imidazoles) react with ATP 30-100-fold faster than do water or alcohols. To complicate the interpretation of the results, it was found that the rate constant for the reaction of F with ATP tetraanion is similar to rate constants for reaction of uncharged amine and oxygen nucleophiles, thus dispelling the myth that reactions of ATP and other phosphoryl anions with anionic nucleophiles are prevented by electrostatic repulsion in aqueous solution. ... 

Section IV,B,l,d Phosphoimidazolium compounds have been prepared by the action of an JV-alkylimidazole on a disubstituted acid chloride of tetracoordinated phosphorus in anhydrous conditions. Phosphoryl imidazolides are of value for the conversion of aldoximes into nitriles. Section IV,B,2,e NMR data indicate that, shortly after complexation of imidazole with iodine or iodine monobromide, the CH and NH ring protons are substituted by halogen. Although complex formation also occurs with 1-methylimidazole, there is no substitution. ... 

Related reactions include the formation of the 2-cyano compounds (190) when 1,2-dimethyl-5-nitroimidazole is heated with nitrosyl chloride or an AT-oxide, and when 2-methyl-l-(o-nitrophenyl)imidazoles (191) cyclize under the influence of iron(II) oxalate (Scheme 98) (74JCS(P1)1970). The last reaction product is contaminated by a large amount of amine reduction product ( 64%) but there is also some cyclization with the 4-methyl isomer of (191). In the presence of trimethylamine, 2-cyanomethylbenzimidazole condenses with acetone to give the unsaturated derivative (192 Scheme 99) (77CPB3087). Neither 2-methylimidazole nor 2-methylbenzimidazole reacts with formamide in the presence of phosphoryl chloride. 

Amino-4-imidazole carboxamide ribotide, a precursor only two steps removed (formylation and cycli-zation) from inosinic acid, can be synthesized by the direct condensation of the imidazole with 5-phosphori-bosyl pyrophosphate. The enzyme catalyzing this reaction was purified from an acetone powder of beef liver. The same enzyme (AMP pyrophosphorylase) catalyzes the condensation of adenine, guanine, and hypoxan-thine. Nucleoside phosphorylase is an enzyme that catalyzes the formation of a ribose nucleoside from a purine base and ribose-1-phosphate. Guanine, adenine, xanthine, hypoxanthine, 2,6-diaminopurine, and aminoimidazole carboxamide are known to be converted to their respective nucleosides by such a mechanism. In the presence of a specific kinase and ATP, the nucleoside is then phosphorylated to the corresponding nucleotide. 

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