Noel J. Cusack

Purines, pyrimidines, and imidazoles part 54. Interconversion of some intermediates in the de novo biosynthesis of purine nucleotides

Ethyl and benzyl 5-amino-1-(2-pyridyl)imidazole-4-carboxylates, obtained from ethyl or benzyl α-amino-α-cyanoacetate, respectively, and ethyl formimidate hydrochloride followed by 2-aminopyridine, were converted into 5-amino-1-(2-pyridyl)-imidazole-4-carboxylic acid which was decarboxylated in situ to 5-amino-1-(2-pyridyl)imidazole. Reaction of 2-N-formylamino-N-(2-pyridyl)acetamide with ammonia and ammonium chloride gave 5-aminoimidazole and a similar reaction with the nucleotide 2-N-formylglycineamide ribotide similarly gave evidence for aminoimidazole formation. 4-Cyano-5-imidazolone, prepared by reaction of 2-cyano-N-formylacetamide with nitrous acid and reduction of the hydroxyimino derivative so produced, with ammonia and ammonium sulphite at 100 °C, gave 5-aminoimidazole-4-carboxamide. Implications of the reactions involved are discussed.

Purines, pyrimidines, and imidazoles. Part XLI. Glycofuranosylamines derived from D-xylose, D-glucose, D-mannose, and L-rhamnose and their use in the synthesis of pyrimidine and imidazole nucleosides

3,5-O-Isopropylidene-D-xylofuranosylamine, 5,6-O-isopropylidene-D-glucofuranosylamine, 2,3-O-isopropylidene-L-rhamnofuranosylamine, and 2,3:5,6-di-O-isopropylidene-D-mannofuranosylamine toluene-p-sulphonates have been prepared in good yield by reactions of the corresponding pyranosylamines with acetone, 2,2-dimethoxypropane, and toluene-p-sulphonic acid. Reaction of the glycofuranosylamines with α-acetyl-, α-cyano-, or N-methyl-α-cyano-β-ethoxy-N-ethoxycarbonylacrylamides gave the corresponding 5-substituted uracil α- or β-glycofuran-osides. Furanose structures were confirmed by periodate titration or periodate oxidation. Assignments of anomeric configurations were in most cases confirmed by n.m.r. spectroscopy. The anomeric structures of the glycofuranosylamines in various solvents were studied by means of n.m.r. spectroscopy and optical rotation measurements. A bis(di-isopropylidenemannofuranosyl)amine of unknown anomeric structure was obtained as a by-product in one reaction. The isopropylidenemannofuranosylamine either with ethyl N-[ethoxycarbonyl-or carbamoyl(cyano)methyl]formimidates, or with ethyl formimidate hydrochloride [to give a mixture of ethyl N-1-(2,3:5,6-di-O-isopropylidene-α- and -β-D-mannofuranosyl)formimidates] followed by ethyl amino(cyano)acetate, gave 2,3:5,6-di-O-isopropylidene-α- and -β-5-amino-4-ethoxycarbonyl or -carbamoyl-imidazole D-mannofuranosides, from which the isopropylidene groups could be removed by aqueous acid. Structures of the aminoimidazole mannofuranosides were confirmed by means of periodate oxidation, n.m.r. and c.d. studies, and conversion of the esters into the corresponding amides.

Synthesis of Adenosine and Adenine Nucleotide Analogs

Analogs of adenosine and adenine nucleotides have proved of considerable value in the elucidation of the pharmacology of naturally occurring purines. Alterations to the purine, ribose, and phosphate moieties have all provided analogs of pharmacological interest, and some of them are considerably more potent receptor agonists and have a more prolonged pharmacological action than the parent nucleosides and nucleotides. This chapter has been written to provide pharmacologists with a general outline of some manipulations peculiar to the chemistry of adenosine and adenine nucleotides and focuses on procedures that are relatively free from unnecessary complexity. The current availability of a large number of key nucleoside intermediates, chemical reagents, and dried purified solvents has eliminated much of the preliminary tedium formerly associated with their preparation. In the descriptions that follow, it is assumed that all solvents are dry and that all reactions are carried out at room temperature unless otherwise stated.