title: Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism.
abstract: Simplifying access to synthetic nucleosides is of interest due to their widespread use as biochemical or anticancer and antiviral agents. Herein, a direct stereoselective method to access an expansive range of both natural and synthetic nucleosides up to a gram scale, through direct glycosylation of nucleobases with 5-O-tritylribose and other C5-modified ribose derivatives, is discussed in detail. The reaction proceeds through nucleophilic epoxide ring opening of an in situ formed 1,2-anhydrosugar (termed "anhydrose") under modified Mitsunobu reaction conditions. The scope of the reaction in the synthesis of diverse nucleosides and other 1-substituted riboside derivatives is described. In addition, a mechanistic insight into the formation of this key glycosyl donor intermediate is provided.
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 16610, Prague 6, Czech Republic.
authors.forename: A Michael
authors.initials: AM
authors.lastname: Downey
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 16610, Prague 6, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Pohl
authors.affiliation: Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843, Prague 2, Czech Republic.
authors.forename: Jana
authors.identifier: http://orcid.org/0000-0001-5144-0688
authors.initials: J
authors.lastname: Roithová
authors.affiliation: Institute of Organic Chemistry and Biochemistry, Czech Academy of Sciences, Flemingovo nám. 2, 16610, Prague 6, Czech Republic.|Department of Organic Chemistry, Faculty of Science, Charles University in Prague, Hlavova 8, 12843, Prague 2, Czech Republic.
authors.forename: Michal
authors.identifier: http://orcid.org/0000-0002-1113-2047
authors.initials: M
authors.lastname: Hocek
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry; D004852:Epoxy Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006031:Glycosylation; D008958:Models, Molecular; D009705:Nucleosides / Q000138:chemical synthesis* / Q000737:chemistry; D012266:Ribose / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D013237:Stereoisomerism
chemical_list: D000970:Antineoplastic Agents; D000998:Antiviral Agents; D004852:Epoxy Compounds; D009705:Nucleosides; D012266:Ribose
keywords: epoxides; glycosylation; nucleosides; riboses; synthesis design