C-Glycosylphosphonyl Analogs of 5-Phosphorylribose 1-α-Diphosphate: II. The “2-Deoxy” Analog

d-ribo-2,5-anhydro-1,3-dideoxy-1-(((dihydroxyphosphinyl)oxy)hydroxyphosphinyl)-6-phosphorylhexitol, compound4,along with 25% of itsd-arabino epimer, was synthesized in 10 steps from 2-deoxyribonolactone. Compound4represents the 2-deoxy analog of the central metabolite 5-phosphorylribose 1-α-diphosphate (PRPP). The analog is a competitive inhibitor of yeast orotate phosphoribosyltransferase (PRTase) withKi/Km(PRPP)= 24 and is thus comparable to otherC-glycosylphosphonyl PRPP analogs reported previously (R. W. McClard, and J. F. Witte (1990)Bioorg. Chem.18,165–178). The analog is an even better inhibitor of both human hypoxanthine-guanine PRTase and glutamine:amido PRTase fromEscherichia coliwithKi/Km(PRPP)values of 16 and 3, respectively. These results support the argument that the cis-diol grouping of nucleotides (or PRPP) plays a very minor role in binding of these substrates to PRTases.