title: Efficient synthesis of 2'-deoxyzebularine and its α-anomer by the silyl method of N-glycosylation. Crystal structures and conformational study in solution.
abstract: 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.
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Ebenryter-Olbinska
authors.affiliation: Institute of General and Ecological Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland.
authors.forename: Janina
authors.initials: J
authors.lastname: Karolak-Wojciechowska
authors.affiliation: Institute of Organic Chemistry, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland. Electronic address: elzbieta.sochacka@p.lodz.pl.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Sochacka
mesh_terms: D002236:Carbohydrate Conformation; D060326:Chemistry Techniques, Synthetic; D018360:Crystallography, X-Ray; D003562:Cytidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D006031:Glycosylation; D008958:Models, Molecular; D012996:Solutions; D013237:Stereoisomerism; D013379:Substrate Specificity
chemical_list: C540597:2'-deoxyzebularine; D012996:Solutions; D003562:Cytidine
keywords: 2′-Deoxynucleosides synthesis; 2′-Deoxyzebularine; Modified nucleosides; Nucleoside conformation; Stereoselective N-glycosylation; Zebularine