Jacobsen, Mikkel Fog2; Knudsen, Martin M.2; Gothelf, Kurt Vesterager4
1 Interdisciplinary Nanoscience Center, Faculty of Science, Aarhus University, Aarhus University2 Department of Chemistry, Faculty of Science, Aarhus University, Aarhus University3 Department of Chemistry, Department of Chemistry, Science and Technology, Aarhus University4 Department of Chemistry, Department of Chemistry, Science and Technology, Aarhus University
A general approach to N-arylation and N-alkenylation of all five DNA/RNA nucleobases at the nitrogen atom normally attached to the sugar moiety in DNA or RNA has been developed. Various protected or masked nucleobases engaged readily in the copper-mediated Chan-Lam-Evans-modified Ullmann condensation with a range of different boronic acids at room temperature and were subsequently converted to the corresponding deprotected or unmasked adducts. Different N3-protecting groups were examined in the case of thymine, where the benzoyl group afforded the highest yields. A 4-alkylthio-substituted pyrimidin-2(1H)-one served as both a cytosine and a uracil precursor and was N-arylated and N-alkenylated in high yields. Adenine was efficiently and selectively N-arylated and N-alkenylated at the N9 position by employing a bis-Boc-protected adenine derivative, while a bis-Boc-protected 2-amino-6-chloropurine served as guanine precursor and could also be selectively N9-arylated and N9-alkenylated.
Journal of Organic Chemistry, 2006, Vol 71, Issue 24, p. 9183-9190