Aryl glucuronides

Koenigs-Knorr synthesis of aryl glucuronides. Steroid glucuronides of estrone, 17 /)-estradiol, estriol, and equilenin can be prepared in excellent yield by the reaction of the phenolic steroid with the bromo sugar (I) in toluene using cadmium carbonate as... 

Conrow, R B, Bernstein, S, Steroid Conjugates. VI. An improved Koenigs-Knorr synthesis of aryl glucuronides using cadmium carbonate, a new and effective catalyst, J. Org. Chem., 36, 863-870, 1971. 

Figure 1. Strong anion exchange LC separation of phenols, aryl glucuronides and aryl sulfates using a UV absorbance detector. Compounds eluted are 1, phenol 2, 4-nitrophenol 3, 1-naphthol 4, phenyl-be ta-D-glucuronide 5, 4-nitrophenyl-beta-D-glucuronide 6, 1- naphthyl-beta-D-glucuronide 7, phenyl sulfate 8, 4-nitrophenyl sulfate 9, 1-naphthyl sulfate. (Reproduced with permission from Ref. 19. Copyright 1989 Elsevier Science Publishers B.V.)...

Figure 3. Selected reaction monitoring of aryl glucuronides and sulfates eluted from a strong anion exchange column. Glucuronides are detected by neutral loss of 176 mass units as in phenyl-beta-D- glucuronide (269" --> 93"), 4-nitrophenyl-beta-D-glucuronide (314" --> 138"), and 1-naphthyl-beta-D-glucuronide (319" > 143"). Sulfate conjugates are detected by neutral loss of S03 as in phenyl sulfate (173 — > 93"), 4-nitrophenyl sulfate (218 — > 138") and 1-naphthyl sulfate (223" > 143"). Compounds with a 4-nitrophenol moiety are detected with Q1 at m/z 138 and Q3 at m/z 108 scan 74, 4-nitrophenol scan 133, 4-nitrophenyl-beta-D-glucuronide and scan 269, 4- nitrophenyl sulfate.

The LC/UV separation was readily adapted to TSP LC/MS with some loss in chromatographic efficiently. The band broadening encountered restricted the resolution of low k compounds, but was inconsequential in the baseline separation of the the aryl glucuronide and aryl sulfate compounds studied. Losses in efficiency observed in TSP LC/MS stress the importance of chromatographic retention and phase selectivity in obtaining high quality, interference free LC/MS spectra. 

Hydrolysis of /3-glucuronides (I r = alkyl, aryl, or acyl) by the enzyme from mammalian or non-mammalian sources is powerfully and competi-... 

Total radioactivity Unchanged ciramidol Aryl-0-glucuronide Alicy die- 0 -glucuro nide... 

Polycyclic aromatic amines are readily absorbed into the body via the gastrointestinal tract, where metabolic activation takes place. Aryl amines are N-hydroxylated and subsequently glucuronidated via uridine diphosphate (UDP)-glucuronosyl transferase or sulfated by sulfotransferases, N-acetylation of the amine, and 0-acetylation of the N-hydroxy amine can occur. 

Sulfation is another common form of conjugation predominately found with phenolic compounds however, sulfate esters can also be formed with alcohols, aryl-amines, and N-hydroxy compounds. Sulfation involves the transfer of S03 from 3 -phosphoadenosine-5 -phosphosulfate (PAPS) to one of the above-mentioned functional groups by an enzyme-catalyzed reaction involving the cytosolic enzymes (sulfotransferases), as illustrated in Fig. 24 [11]. It is common to find phenolic compounds that are metabolized by both sulfation and glucuronidation, as they are often competing pathways. However, sulfation has a significant limitation... 

Six hours after intravenous administration of 0.08 mg/kg [ C]-benzo[a]pyrene to rabbits. 30% and 12% of the dose was excreted in the bile and urine, respectively (Chipman et al. 1982). Excretion of activity into the bile was biphasic over a period of 30 hours with apparent half-lives of 0.27 and 4.623 hours for the rapid and slow phases, respectively. Treatment of the bile and urine with p -glucuronidase and aryl sulfatase increased the amount of activity in the bile and urine that was extractable into ethyl acetate indicating the presence of glucuronide and sulfate conjugates. 

Bile acid glucuronides may be hydrolyzed by -glucuronidase (EC 3.2.1.31) from bovine liver or the digestive juice of Helix pomatia (S41). The latter enzyme preparation also contains sulfatase activity (S41), but this is likely to be an aryl sulfatase which may not use bile acid sulfates as substrates. 

Bunamiodyl (B19, S26) and iodopanoic acid (S17) cause an elevation of BSP retention. These compounds, and the related iodinated aryl compound iodipamide, competitively inhibit the enzyme S-aryl glutathione transferase (B38). However, these compounds also affect the excretion of bilirubin (B21, B33), which is excreted as a glucuronide, of indocyanine green (H4), which is not conjugated by the liver, and of conjugated bilirubin (B21). Bunamiodyl and iodipamide reduce the uptake of BSP by liver slices (B6, B7) and by the isolated perfused liver (B19). 

---