Conjugates xenobiotic sulfate, synthesis

Reactions with sulfur trloxlde. Sulfur trloxlde (SO3) may react violently with nucleophiles unless the conditions are well controlled and this route Is not commmonly used for syntheses of xenobiotic sulfate conjugates. However a method suitable for both macro and micro scale synthesis of ascorbic acid 2-P sj sulfate (Figure 6A) was recently reported where the SO3 was Introduced to the substrate dissolved In DMF at -180"C (7 ). The reaction was completed at -15 C In 30 min and gave a 74Z yield of the 2-0-sulfate. 

Modulation of liver and kidney function. Nutrients and xenobiotics (such as secondary metabolites) are transported to the liver after resorption in the intestine. In the liver, the metabolism of carbohydrates, amino acids, and lipids takes place with the subsequent synthesis of proteins and glycogen. The liver is also the main site for detoxification of xenobiotics. Lipophilic compounds, which are easily resorbed from the diet, are often hydroxylated and then conjugated with a polar, hydrophilic molecule, such as glucuronic acid, sulfate, or amino acids (312). These conjugates, which are more water soluble, are exported via the blood to the kidney, where they are transported into the urine for elimination. 

Conjugation of 0-, N- and S-contalnlng functional groups with sulfate Is very common In animal systems. Sulfate Is transferred from adenosine 3 -phosphate-5 -sulfatophosphate (PAPS) by a variety of transfer enzymes. The mechanisms for sulfation of xenobiotics (74,75) and the chemistry of sulfate esters and related compounds and the synthesis of these have been reviewed (75-77). Syntheses of 0-, N- and S-sulfate conjugates of xenobiotics may be carried out by the methods described below. 

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