Synthesis Of 9-(1-Deoxy-1-phosphono-β-D-psicofuranosyl)-1,9-dihydro-6H-purin-6-one as a Potential Transition State Analog Inhibitor of Purine Nucleoside Phosphorylase
- 1 January 1992
- journal article
- research article
- Published by Taylor & Francis in Nucleosides and Nucleotides
- Vol. 11 (1) , 97-119
- https://doi.org/10.1080/07328319208021155
Abstract
A fifteen-step synthesis of the proposed purine nucleoside phosphorylase (PNP) transition state analog inhibitor 9-(1-deoxy-1-phosphono-β-D-psicofuranosyl)-1,9-dihydro-6H-purine-6-one (2) is described starting with 1,2:4,5-disopropylidene-β-D-psicopyranose (12). Catalytic hydrogenation of 9-[3-O-benzyl-1-(dibenzyloxy-phosphinyl)-1-deoxy-β-D-psicofuranosyl]-6-benzyloxypurine (27b) under basic conditions gave the unstable 2 which was found to have a half-life of 39 min at pH 7 and 81 min at pH 8. The low PNP inhibitory activity found for 2 (IC50 = 25 μM at 50 mM phosphate concentration) may be due entirely to the presence of the decomposition product hypoxanthine which is itself an inhibitor (IC50 = 8.6 μM).Keywords
This publication has 25 references indexed in Scilit:
- Aspects of the purine nucleoside phosphorylase (PNP) deficient state produced in normal rats following oral administration of 8-amino-9-(2-thienylmethyl)guanine (PD 119,229), a novel inhibitor of PNPInflammation Research, 1987
- Inhibitors of human purine nucleoside phosphorylase. Synthesis, purine nucleoside phosphorylase inhibition, and T-cell cytotoxicity of 2,5-diaminothiazolo[5,4-d]pyrimidin-7(6H)-one and 2,5-diaminothiazolo[4,5-d]pyrimidin-7(6H)-one. Two thioisosteres of 8-aminoguanineJournal of Medicinal Chemistry, 1986
- Phosphono Nucleoside. 1. Synthesis of 2,3'-Anhydro-1'-deoxy-1'-phosphono-1-b-D-fructofuranosyl UracilHETEROCYCLES, 1986
- 2'-deoxyguanosine toxicity for B and mature T lymphoid cell lines is mediated by guanine ribonucleotide accumulation.Journal of Clinical Investigation, 1984
- Methylation of adenosine in strongly alkaline medium: preparation and properties of O'-methyl derivatives of adenosine and N6-methyladenosineBiochemistry, 1976
- Synthesis of 7- and 9β-D-psicofuranosylguanine and their 1'-deoxy derivativesCollection of Czechoslovak Chemical Communications, 1974
- Synthesis of 1-β-D-psicofuranosyluracil and 1-β-D-psicofuranosylcytosineCollection of Czechoslovak Chemical Communications, 1974
- The synthesis of phosphonic acid analogues of purine ribonucleotides: an exception to the trans ruleJournal of the Chemical Society D: Chemical Communications, 1969
- Ultra-violet Extinction Coefficients of some Muscle Nucleotides and Purines at pH 7.0 and in 2 N Hydrochloric AcidNature, 1966
- Purine Nucleosides. IX. The Synthesis of 9-β-D-Ribofuranosyl Uric Acid and Other Related 8-Substituted Purine Ribonucleosides1Journal of the American Chemical Society, 1965