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Updated: Jul 18, 2026

Free Radicals in Chemical Biology: from Chemical Behavior to Biomarker Development
Published on: April 15, 2013
Synthesis of 3'-C-substituted thymidine derivatives by free-radical techniques: scope and limitations
Derek Horton1, Kuangmin Chen, Zaesung No
1Department of Chemistry, American University, 4400 Massachusetts Avenue, Washington, DC 20016, USA. carbchm@american.edu
Abstract:
The scope and limitations of radical-mediated 3'-C-substitution of pyrimidine nucleosides was evaluated with 5'-O-(tert-butyldimethylsilyl)thymidine or its tert-butyldiphenylsilyl analogue having thionoester or thionoamide groups at O-3', including (methylthio)thiocarbonyl, (phenoxy)thiocarbonyl, (pentafluorophenoxy)thiocarbonyl, and (1-imidazolyl)thiocarbonyl. Their reaction with acrylonitrile, methyl acrylate, and allyltributyltin under radical-generating conditions affords corresponding 3'-C-alkylated products, together with the product of simple deoxygenation at C-3'. The conditions for optimizing the yield of 3'-C-substituted product are presented.
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