Sulfation xenobiotics with sulfuric acid

These compounds contain the fragment R as an alkyl or aryl moiety. In other words, they result from the esterification of an alcohol or a phenol with nitrous acid, nitric acid, phosphoric acid, sulfuric acid, or sulfamic acid, respectively. Many of the esters to be examined in this chapter must be activated prior to eliciting their effects, e.g., the organic nitrites and nitrates, which act as donors of nitric oxide or an analogous molecule, and phosphates, which are activated by hydrolysis or even by phosphorylation (antiviral agents). Sulfates are very seldom active or used as prodrugs, but they have significance as metabolites and as industrial xenobiotics. 

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. 

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