Synthesis of N-hydroxyacetaminophen, a postulated toxic metabolite of acetaminophen, and its phenolic sulfate conjugate.
The synthesis of N-hydroxyacetaminophen (N-acetyl-N-hydroxy-p-aminophenol, 4), a postulated toxic metabolite of acetaminophen (N-acetyl-p-aminophenol, 3), and its phenolic sulfate conjugate (potassium N-acetyl-N-hydroxy-p-aminophenyl sulfate) (13) is described. Potassium p-nitrophenyl sulfate was reduced to the hydroxylamine, acetylated, and treated with sulfatase to yield N-hydroxyacetaminophen. The structures assigned are supported by the spectral data (IR, UV, MS, 1H NMR, and 13C NMR). N-Hydroxyacetaminophen was found to be moderately unstable at physiological pH and temperature, whereas it phenolic sulfate conjugate was stable.
D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D004355:Drug Stability; D006207:Half-Life; D006863:Hydrogen-Ion Concentration; D013431:Sulfates / Q000138:chemical synthesis; D013696:Temperature
D013431:Sulfates; D000082:Acetaminophen; C017372:N-hydroxyacetaminophen