NOVEL ZWITTERIONIC STRUCTURE AND AN UNUSUAL SUGAR RING CONFORMATION IN 5-IODO-5'-AMINO-2',5'-DIDEOXYURIDINE, AN ANTI-VIRAL NUCLEOSIDE

The three-dimensional structure of 5-iodo-5'-amino-2', 5'-dideoxyuridine, a potent inhibitor of herpes simplex virus, was determined by X-ray crystallography. The crystals belong to the orthorhombic space group P 212121 and the cell dimensions are a = 7.892 (1), b = 9.332 (1), and c = 15.749 (2) Å. Intensity data were measured with a diffractometer and the structure was solved by the heavy-atom method. Least-squares refinement, which included hydrogen atoms, converged at R = 0.047. The structure is zwitterionic, with a protonated 5'-NNH2 group and a negative charge on N(3) in'the pyrimidine ring. The glycosyl bond is in the anti conformation (xcn = 53.6°) and the exocyclic -CH2NH3+ group is gauche-trans. The deoxyribose ring has the unusual O(1') endo pucker. 1HNMR spectroscopy was used to determine the conformation in solution. The spectra indicate an anti conformation about the glycosyl bond and equal contributions of the three staggered side-chain rotamers. The sugar ring may consist of a 36:64 equilibrium mixture of 3E and 2E conformers. It is pointed out, however, that the conventional interpretation may be inadequate, and that there may be a significant contribution of an O(1') endo puckered ring. © 1979, American Chemical Society. All rights reserved.