Glucuronides, ester ether

Glucuronidation of Ether or Ester (here shown via UDP-Glucuronic acid)... 

Acyl glucuronides (i.e., ester glucuronides of general structure 11.6) are formed as conjugates of carboxylic acids. These compounds are rather uniquely reactive a) they are far more sensitive to chemical hydrolysis than ether... 

Figure 4.50 Formation of ether and ester glucuronides of phenol and benzoic acid, respectively.

A typical glucuronide of type I is benzoyl /3-D-glucuronide (R = CaH5-) and of type II phenyl /3-D-glucuronide (R = C6H5-), which are, respectively, metabolites of benzoic acid and phenol in most species. Glucuronides of types I and II are often designated ester and ether ... 

Structural details of both are discussed by Bray.4 In the literature, type III has often been called an ether glucuronide and the type shown in IV has been called an ester glucuronide. ... 

Over 70% of a lethal dose of eugenol was recovered from the urine of rabbits after death. The administration of single 200 mg doses to rats was also reported to increase urinary output of ethereal glucuronides of 33-35 mg/rat in 12 hours compared to the control value of 4 mg/rat. Ester glucuronide values were unchanged. Subcutaneous injection of 0.1 mL of purified eugenol in adult Walter Reed white rats caused necrosis and inflammation at the injection site [29-33]. 

In contrast to the reduction in activity observed in the 3-ether series, the 6-sulfate ester and the 6-glucuronide each exhibit a greater analgesic potency than morphine.<97,98)... 

Disposition in the Body. Well absorbed after oral administration. Up to about 80% of a dose is excreted in the urine in 24 hours, mostly as the ester and ether glucuronides. Less than 3% of a dose is eliminated in the faeces. 

Renal metabolism of isoproterenol [171], bumet-anide [163], cimetidine [172] and N-methylnicotina-mide [173] has been reported. Renal metabolites may have different mode of excretion [174], and may be more nephrotoxic than the original substance [175]. Renal glucuronidation may be substantial as in the case of morphine [176]. Xenobiotic glucuronidation can proceed by linkage through an ether or an ester bound. 

DEHP previously converted in its ferf.-bytyldimethylsilyl derivatives. For the analysis of the intact conjugates of DEHP metabolites by GC, Egestad et al. " prepared the methyl ester trimethylsylil ether derivatives of the major glucuronides. On the other hand, Pietrogrande et al. performed direct GC analysis of the enzymatic hydrolysis products of phthalate esters conjugates without any derivatization step. 

The biotransformation of salicylates takes place in many tissues, but particularly in the liver. The three chief metabolic products are salicyluric acid (the glycine conjugate), the ether or phenolic glucuronide, and the ester or acyl glucuronide. 

Ester and ether glucuronides of difluslnal ( 2, -dlf luoro- l-hydroxy-3-blphenylcarboxylic acid) have been separated by reversed-phase h.p.l.c. and their Identities confirmed through acid, base, or enzymic prehydrolysis of samples. 

UDP-glucuronic acid can be transferred to cortisol to form an ether 0-glucuronide bilirubin to form an ester 0-glucuronide aniline to form an amide A-glucuronide mercaptobenzothiazole to form a thioether S-glucuronide. 

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