Steroids, glucosiduronic acids

Conrow and Bernstein63 recommended the use of cadmium carbonate instead of silver salts to prepare glucosiduronic acids of phenolic steroids. The yields are usually better than those obtained by use of silver salts. Rohle and Breuer64 also used cadmium carbonate in the synthesis of a glucosiduronic acid of estra-l,3,5(10)-trien-2,3,17/3-triol 17-monoacetate, which is oxidizable with silver salts. Thus, methyl tri-O-acetyl-a-D-glucopyranosyluronate bromide (27), on reaction with estrone (28) afforded 3-0-(methyl 2,3,4-tri-O-acety 1 -/3-D-glucopy-ranosyluronate)estrone (29). 

Both the Koenigs-Knorr synthesis and catalytic oxidation may be utilized for the preparation of the steroid D-glucosiduronic acids. The first method is used if the steroid structure is altered by catalytic oxidation, for... 

Some mammalian organs, particularly the liver and kidney, have the ability to convert numerous aliphatic or aromatic alcohols and carboxylic acids into their respective /3-D-glucosiduronic acids these can be transported in the blood or excreted through the urine or bile. This reaction pertains not only to such foreign substances as drugs, but also to such important endogenous compounds as steroid hormones, thyroxine, or bilirubin. 

Although these enzymes are effective means of cleaving urinary steroid glucosiduronic acids, their high cost and relatively slow action militate against their use at present for routine assay purposes. The conditions used for deconjugation with /3-glucuronidase are summarized in Table II. 

As far as is known at the present time, the enzymatic hydrolysis of steroid glucosiduronic acids leads to the release of the free steroids without concomitant formation of transformation products. 

The sulfates of saturated ketosteroids are readily split under the conditions of acid hydrolysis described above (Section III,1) which were found effective for the cleavage of glucosiduronates. However, their cleavage may also be accomplished under very much milder conditions, as was shown by Lieberman and Dobriner (79) and subsequently confirmed by Buehler et at. (14) (Table III, method A). Continuous extraction with ether at pH 0.7 for 24 to 48 hours gives a quantitative recovery of the free steroid. The hydrolysis of the sulfate esters takes place without inversion of stereochemical configuration (82). 

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