Utility of Purinyl Radicals in the Synthesis of Base-Modified Nucleosides and Alkylpurines: 6-Amino Group Replacement by H, Cl, Br, and I

Article abstract of DOI:10.1021/jo01308a004

When 9-substituted adenines are treated with n-pentyl nitrite in hydrogen atom donating solvents and the resulting reaction mixtures are warmed and photolyzed with visible light, the corresponding 9-substituted purines are isolated.The conversion apparently involves homolysis of the intermediate 6-diazonium salts or azo compounds to produce purinyl radical intermediates.These purinyl radicals can subsequently abstract hydrogen atoms from solvent molecules.We have utilized our deamination procedure for the direct synthesis of the antitumor antibiotic nebularine from adenosine.When the deaminations of 9-substituted adenines are conducted in dry CCl4, CHBr3, or CH2I2, the corresponding 6-chloro-, 6-bromo-, and 6-iodopurines are isolated in good yields.There appears to be no detectable hydrogen abstraction in competition with halogen abstraction in the cases of CHBr3 and CH2I2 solvents.These transformations provide shortened preparative pathways to intermediates useful in the synthesis of other base-modified purines.Under appropriate reaction conditions, conversions to the 6-6' dimers also may be possible.The type of transformation in this report represents one of the first examples of the use of neutral purinyl radicals in nucleic acid chemistry.