Pyridazine nucleosides. The structure and conformational analysis of 5-hydroxy-2-(1-β-D-ribofuranosyl)-3(2H)-pyridazinone

Abstract

The crystal structure of the doubly modified nucleoside 5-hydroxy-2-( 1 -fl-D-ribofuranosyl)-3 (2H)-pyridazinone or 3-deaza-6-azauridine (C9HI2N206, M r = 244.206) has been determined using three-dimensional X-ray counter data. The uridine analog crystallizes in the monoelinic space group P21 with two molecules in a unit cell of dimensions a = 7. 136 (7), b = 7.636 (7), c = 10.119 (8) A, and fl= 101.54 (6) °. D O (by flotation in tetrahydrofuran-tribromomethane) = 1.50, De= 1.504 Mg m -3, #(Cu Ka)= 1.06 mm -~. The structure was solved by direct methods and refined by full-matrix least squares using 848 independent data with I > 3a

Structure of 8-azaadenosine hydrochloride

“…8-Azapurine nucleosides seem to prefer a syn or a near-syn (high-anti) conformation, the latter having the glycosyl torsion angle [N(8)---N(9)--C(l')---O(4')] = 100 ___ 30 ° (Prusiner, Brennan & Sundaralingam, 1973;Singh & Hodgson, 1974a, 1977aAbola, Sims, Abraham, Lewis & Townsend, 1974;Koyama, Umezawa & Iitaka, 1974;Sprang, Scheller, Rohrer & Sundaralingam, 1978;Birnbaum, Brisson, Krawczyk & Townsend, 1985). 6-Azapyrimidine nucleosides, which also lack an H 0108-2701/89/101586-04503.00 atom next to the glycosyl bond, seem to prefer the high-anti conformation exclusively (Singh & Hodgson 1974b,c;Schwalbe & Saenger, 1973;Banerjee & Saenger, 1978;Graves, Hodgson, Katz, Wise & Townsend, 1978;Graves & Hodgson, 1981). The natural antibiotic formycin A, which has a C----C glycosyl bond and is an 8-azapurine nucleoside, has a glycosyl torsion angle of 109.5 ° (Prusiner et al, 1973) which is a high-anti conformation but, when protonated, it goes over to the classical syn conformation with a X of 210"7° (Koyama et al, 1974).…”