Oxidation 3-oxosteroid

Oxides of nitrogen vapor la 86 11 -Oxoanderosterone lb 78 11 -Oxolanostenyl acetate la 62 Oxomemazine lb 354 17-Oxosteroids lb 78,79 Oxprenolol la 299 lb 268 Oxycodeinone lb 280 Oxydemeton methyl lb 164,165 Oxyhemoglobin, dipole moment la 97 Oxymorphone lb 280 Oxypertin lb 354 Oxytetracycline lb 271... 

In 3-oxosteroid A4-steroid 5)3-reductase deficiency, key intermediates for cholic and chenodeoxycholic synthesis, 7a-hydroxy-4-cholesten-3-one and 7a,12a-dihy-droxy-4-cholesten-3-one undergo side-chain oxidation and conjugation to produce... 

Betamethasone is well absorbed after oral administration to be extensively bound to plasma proteins in humans, dogs, cows, and rats. Its metabolism does not differ of the other corticosteroids, involving oxidation of the 11 -hydroxyl group to ketone, reduction of the ketone group at the position C-20 to give the corresponding alcohol, and hydroxylation at the C-6 position and loss of the C-17 side chain to give 17-oxosteroids. 

Oxidative photolysis of the acetyllQrdrazones of 17-oxosteroids gives the lactam together with its 13-a isomer (H. Suginome and T. Uchida, J. chem. Soc. Perkin I, 1980, 1356). 

The reduction of a 3-oxosteroid, catalyzed by 3a-hydroxysteroid dehydrogenase from rat liver, has been shown to involve transfer of a hydride ion from the A-side of NADPH to the 3j -position of the steroid (44,52). The oxidation of 4-cholestene-3a,7a-diol into 7a-hydroxy-4-cholesten-3-one, catalyzed by the same enzyme preparation, has also been shown to involve the A-side of NADPH (52). It remains to be established whether or not Zl -3a-hydroxysteroid dehydrogenase activity is due to enzyme(s) different from 3a-hydroxysteroid dehydrogenase(s). 

Fig. 32.1. The classical ( neutral ) pathway for the synthesis of bile acids from cholesterol, where the modification of the steroid nucleus occurs prior to side-chain modification. Also illustrated are the inborn errors of bile acid synthesis and the resulting abnormal metabolites. 32.1, 3) -hydroxy-A -C27-steroid dehydrogenase (3) -HSDH) deficiency 32.2, A -3-oxosteroid 5 -reductase deficiency 32.3, sterol 27-hydroxylase deficiency (cerebrotendinous xanthomatosis, CTX) PD, peroxisomal disorders (defects of peroxisome biogenesis and peroxisomal j -oxidation). The abnormal metabolites that are readily detected by analysis of urine by LSI-MS are shown in boxes. Cholic acid can also be synthesised from 5 -cholestane-3a,7a,12a,25-tetrol this is the so-called microsomal or 25-hydroxylase pathway of cholic acid synthesis, which provides an alternative route for side-chain modification other than peroxisomal j -oxidation...

Reaction rates can be smaller for the conjugate than for the free homolog, as is the case for the oxidation of androstenediol glucuronide by the liver enzyme, when compared to testosterone (Milgrom and Baulieu, 1968) and for estradiol sulfate when compared to estradiol (Warren and Crist, 1967) with the placental enzyme. But, estriol sulfate is oxidized at a higher rate than estriol by a human red cell reductase (Jacobsohn and Hochberg, 1967) and testosterone sulfate is reduced faster than the free compound by a microsomal A -3-oxosteroid reductase preparation (Wu and Mason, 1965). 

The term 17-oxogenic steroids is used because, in their determination, the corticosteroids and their metabolites are oxidized to 17-oxosteroids which can then be determined by the Zimmer-mann reaction. This is the Norymberski procedure. The initial... 

Step in their determination consists of borohydride reduction, by which the corticosteroids and their metabolites are converted to their dihydroxy derivatives. At the same time, the 17-oxo steroids present are reduced to secondary alcohols which are not affected by bismuthate or periodate (see below) and do not give the Zimmermann reaction. The next step consists of bismuthate or periodate oxidation, by which the dihydroxy derivatives are converted to 17-oxosteroids. These are then estimated by their reaction with m-dinitrobenzene in alcoholic alkali to give a purple compound (the Zimmermann reaction). 

---