Synthesis of 5-amino-1-(5-deoxy-.beta.-D-ribofuranosyl)imidazole-4-carboxamide and related 5'-deoxyimidazole ribonucleosides

Abstract

5-Amino-1-(beta-D-ribofuranosyl)imidazole-4-carboxamide (1, AICA ribonucleoside) was converted in two steps to 5-amino-1-(5-deoxy-5-iodo-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carboxamide (3) which was hydrogenated in the presence of Pd/C to yield 5-amino-1-(5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carboxamide (4). The dehydration of 4 yielded 5-amino-1-(5-deoxy-2,3-O-isopropylidene-beta-D-ribofuranosyl)imidazole-4-carbonitrile (7). The compounds 3, 4, and 7 were deblocked with formic acid to furnish 5-amino-1-(5-deoxy-5-iodo-beta-D-ribofuranosyl)imidazole-4-carboxamide (6). 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide (5), and 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carbonitrile (8), respectively. Compound 8 was acetylated and then deaminated to give 1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)imidazole-4-carbonitrile (11). The compounds 8 and 11 were converted into 5-amino-1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-thiocarboxamide (9) and 1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-thiocarboxamide (12), respectively. The synthesis of 1-(5-deoxy-beta-D-ribofuranosyl)imidazole-4-carboxamide (13) was achieved for the first time by the treatment of 11 with hydrogen peroxide in the presence of ammonium hydroxide. The compounds were tested for antibacterial, antifungal, and antiviral activity, with 5 and 6 significantly inhibitory to Staphylococcus aureus.

Synthesis and biological activity of certain derivatives of oxazinomycin and related oxadiazole nucleosides

“…3 -O Acetyl-2 -chloro-2 -deoxyoxazinomycin (8). 2-Acetoxybenzoyl chloride (4.0 g) was added to a suspension of oxazinomycin (1.25 g) in acetonitrile (15 mL).…”

“…The synthesis of 2'-deoxyoxazinomycin was also investigated due to its structural similarity with various naturally occurring pyrimidine 2'-deoxyribonucleosides. A general procedure for the synthesis of 2'-chIoro-2'-deoxy-S'-O-acetylpyrimidine nucleosides has been described by Reichman et al10 Following a similar procedure, oxazinomycin was refluxed with 2-acetoxybenzoyl chloride in acetonitrile to provide 3'-0-acetyl-2'-chloro-2'-deoxyoxazinomycin (8). The structure of 8 was determined on the basis of elemental analysis and NMR.…”

“…Alternatively, the iodination of oxazinomycin followed by catalytic hydrogenation also provided 6. Oxazinomycin was treated with 2-acetoxybenzoyl chloride to provide 3'-0-acetyl-2'-chloro-2'-deoxyoxazinomycin (8) which, after reduction with tributyltin hydride, provided 3'-0acetyl-2'-deoxyoxazinomycin (9). Oxazinomycin was also converted into oxazinomycin 5'-phosphate (10) and into 04,2'-anhydrooxazinomycin (11).…”

Fluorinated pyrimidine nucleosides. 3. Synthesis and antitumor activity of a series of 5'-deoxy-5-fluoropyrimidine nucleosides

“…b'-Deoxy compounds are potentially interesting medicinal agents, since such materials cannot be phosphorylated and incorporated into nucleic acids and thus offer the possibility of reduced toxicity and increased specificity. Srivastava et al 2 have synthesized a series of b'-deoxyimidazole nucleosides for evaluation as potential antiviral or antibacterial agents; although no antiviral activity was detected, some antibacterial effects were observed. Falco and Fox3 synthesized '-deoxy-ara-C from '-deoxyuridine for studies with the enzyme deoxycytidine deaminase; this compound was completely deaminated by both human liver and mouse kidney deaminases but was inactive against L1210 leukemia or Burkitts cell cultures.…”

Chemically Defined Medium for Susceptibility Testing of Antimicrobial Agents

“…In our laboratory, in vitro evaluation of potential chemotherapeutic agents that may act as metabolic inhibitors required a chemically defined medium (1,11,13,14). This medium needed to be simple and inexpensive to prepare.…”