guanosine-monophosphate and Leukemia

Topics: Animals; Apoptosis; Cells, Cultured; Gene Expression Profiling; Gene Expression Regulation, Leukemic; Granulocytes; Green Fluorescent Proteins; Guanosine Monophosphate; Humans; Interferon Regulatory Factors; Leukemia; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Monocytes; Proto-Oncogene Proteins c-bcl-2

Methyl 2,3-O-isopropylidene-D-ribofuranoside (1) was converted to 1-O-acetyl-5-bromo-5-deoxy-2,3-di-O-benzoyl-D-ribofuranose (6) in five steps with good yield. The Arbuzov condensation of compound 6 with triethyl phosphite resulted in the synthesis of 1-O-acetyl-2,3-di-O-benzoyl-5-deoxy-5-(diethoxyphosphinyl)-D-ribofuranos e (7). Compound 7 was used for direct glycosylation of both purine and pyrimidine bases. The glycosylation was accomplished with the dry silylated heterocyclic base in the presence of trimethylsilyl triflate. Deblocking of the glycosylation products gave exclusively the beta anomer of the 5'-phosphonate analogues of 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]adenine (13), 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]guanosin e (16), 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]hypoxant hine (17), and 9-[5'-deoxy-5'-(dihydroxyphosphinyl)-beta-D-ribofuranosyl]cytosine (15), described here for the first time. The target compounds as well as their intermediates showed no in vitro antiviral or antitumor activity, although phosphorylation of 15 and 16 to di- and triphosphate analogues was demonstrated with use of isolated cellular enzymes.

Topics: Adenosine Monophosphate; Animals; Chemical Phenomena; Chemistry; Colonic Neoplasms; Cytidine Monophosphate; Cytosine Nucleotides; Guanine Nucleotides; Guanosine Monophosphate; Humans; Inosine Monophosphate; Inosine Nucleotides; Leukemia; Leukemia L1210; Magnetic Resonance Spectroscopy; Mice; Molecular Structure; Neoplasms; Phosphorylation; Spectrophotometry, Ultraviolet; Structure-Activity Relationship; Tumor Cells, Cultured; Viruses

Topics: Acute Disease; Adenosine Monophosphate; Adult; Aged; Bone Marrow; Cytidine Monophosphate; Erythrocytes; Female; Guanosine Monophosphate; Humans; Leukemia; Male; Middle Aged; Ribonucleotides; Uridine Monophosphate