Studies on nucleotide analogs : I. Synthesis of two 9-α- D-mannofuranosyladenine phosphates, and their inhibition of adenylate kinase

• Published in: Carbohydrate research 1973-09, Vol.30 (1), p.133-142
• Main Authors: Taylor, Marilyn J., Kohn, Bernice D., Taylor, William G., Kohn, Paul
• Format: Article
• Language: English
• Subjects: Adenine Nucleotides - chemical synthesis; Adenosine Monophosphate; Carbon Radioisotopes; Chemical Phenomena; Chemistry; Chromatography, Gas; Chromatography, Ion Exchange; Chromatography, Paper; Chromatography, Thin Layer; Hydrolysis; Kinetics; Magnetic Resonance Spectroscopy; Mannose - chemical synthesis; Mass Spectrometry; Oxidative Phosphorylation; Phosphorus; Phosphotransferases - analysis; Phosphotransferases - antagonists & inhibitors
• ISSN: 0008-6215; 1873-426X
• DOI: 10.1016/S0008-6215(00)82180-1

9-α- D-Mannofuranosyladenine ( 1) was quantitatively phosphorylated at O-5 by phosphoryl chloride in the presence of triethyl phosphate, giving phosphate 2. Treatment of 9-(2,3- O-isopropylidene-α- D-mannofuranosyl)adenine ( 3) with phosphoryl chloride-trimethyl phosphate, followed by hydrolysis at pH 1.5 to remove the protecting group, yielded mononucleotides 2 and 4 having the phosphate group at C-5′ and C-6′, respectively. These mononucleotides, chromatographically homogeneous in six solvent systems, were further characterized by their patterns of chromatography on Dowex ion-exchange resin, by their mass spectra, and by phosphorus n.m.r. spectroscopy. Both the 5′- and 6′-phosphates are noncompetitive inhibitors of adenylate kinase (for which a sensitive, accurate, and inexpensive, assay-system was developed). Of the two, the 6′-mononucleotide was the more potent inhibitor of adenylate kinase.