Molecular structure of [4-(4-cyanobenzoyl) phenyl] 1,5-dithio-β-d-xylopyranoside (naroparcil) in the solid state and in solution: An investigation by X-ray crystallography, molecular mechanics calculations, and NMR spectroscopy

✍ Scribed by Jean-Yves Le Questel; Nadine Mouhous-Riou; Serge Pérez

• Publisher: Elsevier Science
• Year: 1996
• Tongue: English
• Weight: 758 KB
• Volume: 284
• Category: Article
• ISSN: 0008-6215
• DOI: 10.1016/0008-6215(96)00013-4

✦ Synopsis

The conformational behavior of a representative of a new class of oral venous antithrombotic agents, [4-(4-cyanobenzoyl) phenyl] 1,5-dithio-/3-D-xylopyranoside (naroparcil) (1) has been characterized by X-ray crystallography, molecular modeling and NMR studies. The crystal structure of 1 belongs to the monoclinic space group P2~, with two independent molecules in the asymmetric unit. The unit cell has dimensions of a = 11.641, b = 8.040, c = 20.020 ,~, and /3 = 102.29 °. The present work provides structural information on the influence of substitution of intracyclic and glycosidic oxygen atoms by sulfur atoms, as well as on the influence of aromatic rings on the carbohydrate moiety. The xylopyranoside ring has the classical 4C 1 conformation. As for the orientations of the phenyl substituent with respect to the xylopyranose the values observed in the two independent molecules are strikingly different (-85 °, -177 °) and (-102 °, 144°). The 1 H-I H NOE across the glycosidic bond has been measured by NOESY experiments. In parallel, a conformational analysis using the crystal coordinates as the starting point has been made using the Tripos force field. The resulting potential energy surface indicates a high flexibility about the glycosidic linkage. The theoretical NMR data were calculated taking into account all the