Glycosylation of Nucleosides
Yonglian Zhang1, Spencer Knapp1
1Department of Chemistry & Chemical Biology, Rutgers The State University of New Jersey , 610 Taylor Road, Piscataway, New Jersey 08854, United States.
The Journal of Organic Chemistry
|March 4, 2016
Summary
Chemists developed new methods for nucleoside O-glycosylation, overcoming challenges with nucleobase reactivity. Optimized conditions and indium(III) triflate enable efficient glycosylation of hydroxyl groups, minimizing unwanted reactions.
Area of Science:
- Organic Chemistry
- Glycosylation Chemistry
- Nucleoside Chemistry
Background:
- Nucleoside O-glycosylation is challenging due to the higher nucleophilicity of the nucleobase compared to the hydroxyl group.
- Achieving selective O-glycosylation requires overcoming inherent reactivity differences between these sites.
Purpose of the Study:
- To develop optimized reaction conditions for efficient and selective O-glycosylation of nucleoside hydroxyls.
- To investigate methods for minimizing nucleobase interference during glycosylation reactions.
Main Methods:
- Utilized thioglycoside and Schmidt imidate donors (1.5 equiv) for glycosylation.
- Employed indium(III) triflate (In(OTf)3) as a donor activating reagent.
- Investigated the reaction of uridine triacetate under developed conditions.
Main Results:
- Successfully achieved efficient O-glycosylation of nucleoside hydroxyls.
- Indium(III) triflate promoted apparent transfer of the glycosyl moiety from the nucleobase to the hydroxyl group, minimizing interference.
- Glycosylation of uridine triacetate yielded products of both O- and N-glycosylation on the pyrimidine ring.
Conclusions:
- Developed optimized conditions for selective nucleoside O-glycosylation.
- Indium(III) triflate is effective in directing glycosylation to the hydroxyl group.
- Further studies are needed to fully understand and control regioselectivity in complex nucleosides like uridine triacetate.
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