Selective N1-alkylation of 2'-deoxyguanosine with a quinolinyl quinone methide.
Nucleobase modification by quinone methides (QMs) has been extensively studied in the past decade, and multiple QM adducts were observed. For 2'-deoxyguanosine (dG), the N (2)-dG alkylation adduct was favored under aqueous buffered conditions over other N1-dG, N7-dG, and N7-guanine adducts. We report in this communication that the N1-dG adduct was selectively formed with a quinolinyl QM in 30% aqueous DMF and 10 mM phosphate buffer (pH 7.0) as a favored dG alkylation product. The quinolinyl QM was formed through the fluoride-induced desilylation and elimination of acetate, and the structure of the N1-dG adduct was fully established by one- and two-dimensional NMR analyses. In addition, the concentration of salt played a significant role in N1-dG adduct formation. Further HPLC analysis indicated that the addition of salt decreased the rate of QM formation from the acetate intermediate, although an in-depth mechanistic study is needed.
Zhou
Qibing
Q
Department of Chemistry, Virginia Commonwealth University, 1001 West Main Street, Richmond, VA 23284, USA. qzhou@vcu.edu
Xu
Ting
T
Mangrum
John B
JB
D000085:Acetates / Q000737:chemistry; D000478:Alkylation; D002021:Buffers; D002851:Chromatography, High Pressure Liquid; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry*; D004126:Dimethylformamide / Q000737:chemistry; D005459:Fluorides / Q000737:chemistry; D006863:Hydrogen-Ion Concentration; D045563:Indolequinones / Q000737:chemistry*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008956:Models, Chemical; D012825:Silicon / Q000737:chemistry; D012997:Solvents / Q000737:chemistry
D000085:Acetates; D002021:Buffers; D018736:DNA Adducts; D045563:Indolequinones; D012997:Solvents; C068040:quinone methide; D004126:Dimethylformamide; D003849:Deoxyguanosine; D005459:Fluorides; D012825:Silicon