3871-66-7Relevant articles and documents
Synthesis of Nucleosides through Direct Glycosylation of Nucleobases with 5-O-Monoprotected or 5-Modified Ribose: Improved Protocol, Scope, and Mechanism
Downey, A. Michael,Pohl, Radek,Roithová, Jana,Hocek, Michal
, p. 3910 - 3917 (2017/03/27)
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.
In search of Flavivirus inhibitors part 2: Tritylated, diphenylmethylated and other alkylated nucleoside analogues
Saudi, Milind,Zmurko, Joanna,Kaptein, Suzanne,Rozenski, Jef,Neyts, Johan,Van Aerschot, Arthur
, p. 98 - 109 (2014/03/21)
Several flaviviruses, such as the yellow fever virus and the dengue virus cause severe and potentially lethal infection in man. Following up on our initial hit 3′,5′-bistritylated uridine 1, a series of alkylated nucleoside analogues were synthesized and evaluated for their in vitro antiviral activities against dengue fever virus and yellow fever virus. Hereto, alkyl and aryl groups were attached at various positions of the sugar ring combined with subtle variation of the heterocyclic base. Among the new series of derivatives, 3′,5′-di-O-trityl-5-fluoro-2′-deoxyuridine (39) was the most efficient in this series and inhibited both yellow fever virus and dengue virus replication with a 50% effective concentration (EC50) of ～1 μg/mL without considerable cytotoxicity. The other fluorinated derivatives proved more toxic. Almost all diphenylmethylated pyrimidine nucleosides with 3′,5′-di-O-benzhydryl-2′-deoxyuridine (50) as the example were endowed with strong cytotoxic effects down to 1 μg/mL.
