Phenol groups sulfate conjugation

Many drugs and metabolites are metabolized by conjugation with sulfate or glucuronic acid as described in Chapter 7. Sulfate conjugates can be hydrolyzed back to the alcohol or phenol. Glucuronide conjugates can involve a wider variety of functional groups and... 

Sulfation is the primary conjugation reaction for substrates with phenol groups or aliphatic alcohols (Sturgill... 

Reactions with persulfate and pyrosulfate. The persulfate (peroxy-dlsulfate Ion, S2O8 ) reaction, also known as the Elba persulfate oxidation, has been Important In synthesis of hydroxylated phenols. The method has occasionally been used for synthesis of 0-sulfate conjugates. For example, 4-hydroxy-2-nltrophenyl sulfate was obtained when 3-nltrophenolate was stirred with potassium peroxydlsulfate at room temperature for 2 days (91,). The persulfate reaction has been used for the sulfation of various phenols and aromatic amines however the yields are usually low to moderate (77 ). The sulfate group Is preferentially Introduced In the 4-posltlon of phenols and In the 2-posltlon of aromatic amines but If these positions are blocked substitution at the 2- and... 

Sulfate conjugation through the phenolic hydroxy group, which yields T4-4 -0-sulfate. 

Sulfate conjugates. A series of enzymes called sulfotransferases add sulfate groups to the same set of compounds that undergo glucuronidation. Thus, phenols would be conjugated to produce sulfates—phenol is converted to phenylsulfate (CeHsOSOs"). 

Sulfation is the primary conjugation reaction for substrates with phenol groups or aliphatic alcohols (Sturgill and Lambert, 1997 Brown, 2001). These reactions are catalyzed by sulfotransferases in the cytoplasm. Agents that undergo sulfation include acetaminophen, morphine, ascorbic acid, and endogenous compoimds like chondroitin, heparin, and some steroids. The pool of available sulfates may become saturated in drug overdoses. 

Figure 749 Acetaminophen has a phenol group that is subject to phase II metabolic conversion into a sulfate conjugate.This changes the ClogP value from +0.49 in the drug to -0.84, increasing the water solubility. This is the major urinary metabolite found in children in whom acetaminophen was administered. (ClogP values were determined using ChemBioDraw Ultra 13.0, Perkin Elmer Informatics, Waltham, MA).

If the foreign molecule already possesses a functional group suitable for a phase 2 reaction, a phase 1 reaction will be unnecessary. Thus, if phenol is administered to an animal, then it may immediately undergo a phase 2 reaction, such as conjugation with sulfate. Alternatively it may undergo another phase 1 type of reaction. The major types of reactions are shown in Table 4.2. 

The formation of sulfate esters is a major route of conjugation for various types of hydroxyl group, and may also occur with amino groups. Thus, substrates include aliphatic alcohols, phenols, aromatic amines, and also endogenous compounds such as steroids and carbohydrates (Figs. 4.56 and 4.57). 

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