Ebenryter-Olbinska Katarzyna, Karolak-Wojciechowska Janina, Sochacka Elzbieta
Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
Institute of General and Ecological Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
Carbohydr Res. 2014 Jun 17;392:7-15. doi: 10.1016/j.carres.2014.03.018. Epub 2014 Mar 28.
2'-Deoxyzebularine and its α-anomer have been efficiently synthesized with relatively high stereoselectivity by a modified procedure of the silyl method of the N-glycosidic bond formation. An SnCl4-catalyzed condensation of silylated pyrimidin-2-one with 1-α-chloro-3,5-di-O-p-toluoyl-2-deoxy-d-ribofuranose under kinetic control condition (-33°C, 1,2-dichloroethane) led to the mixture of β- and α-anomeric nucleosides in 3:1 ratio. Analogous condensation at +35°C (thermodynamic control conditions) provided mainly p-toluoyl protected α-2'-deoxyzebularine (α:β=4:1), easily separated by crystallization from the anomeric mixture. The structures of both 2'-deoxyzebularine anomers were confirmed by X-ray analysis of the crystals and conformational studies in solution performed using an NMR method.
通过改良的N-糖苷键形成的硅烷基化方法，以相对较高的立体选择性高效合成了2'-脱氧泽布勒林及其α-异构体。在动力学控制条件（-33°C，1,2-二氯乙烷）下，用四氯化锡催化硅烷基化的嘧啶-2-酮与1-α-氯-3,5-二-O-对甲苯甲酰基-2-脱氧-D-核糖呋喃糖缩合，得到β-和α-异头核苷的混合物，比例为3:1。在+35°C（热力学控制条件）下进行类似的缩合反应，主要得到对甲苯甲酰基保护的α-2'-脱氧泽布勒林（α:β = 4:1），可通过从异头混合物中结晶轻松分离。通过晶体的X射线分析和使用NMR方法在溶液中进行的构象研究，证实了两种2'-脱氧泽布勒林异头物的结构。
