20-Oxosteroid

Higashi T, Takido N, Shimada K. 2003. Detection and characterization of 20-oxosteroids in rat brains using LC-electron capture APCI-MS after derivatization with 2-nitro-4-trifluoromethylphenylhydrazine. Analyst 128 130. de Hoffman E, Stroobant V. 2001. Mass spectrometry principles and applications, 2nd edn. West Sussex, England Wiley. 

The application of Westphalen and backbone rearrangement reaction conditions (MeN02, Bi(0Tf)3xH20 catalyst) [118] to 16a,17a-epoxy-20-oxosteroids has also been studied [124]. At room temperature and 0.05 eq. of catalyst, low conversion of 16a,17a-epoxy-20-oxopregn-5-en-3p-yl acetate was observed. However, on increasing the temperature to 50 °C, 16a- and 16p-hydroxy-17p-methyl-A13-18-nor pregnane derivatives were formed in near similar amounts from 16a,17a-epoxy-20-oxosteroids (Scheme 33). 

Scheme 33 Bi(OTf)3-xH20-catalyzed rearrangement of 16a,17a-epoxy-20-oxosteroids...

System (3) has been recommended for the separation and determination of 17,21-dihydroxy-20-oxosteroids, including cortisone [142], Prior to introduction into the GC system, treatment with sodium bismuthate in acetic acid at room temperature was performed, followed by addition of aqueous NaOH. The analytes were then extracted with chloroform. The column used was glass column (6 ft x 0.25inch), containing 3% QF-1 on GasChrom Q (100 to 120 mesh), operated at 225°C. Argon (150 mL/min) was used as the carrier gas, and detection was based on a P-ionization detector. It was reported that results obtained with a 1 1 mixture of cortisone and hydrocortisone were accurate to within approximately 1%. 

Oxygen may be added by means of peracids to the double bond of enamines prepared from 20-oxosteroids. The 17,20-epoxides obtained may be readily hydrolyzed to 17a-hydroxy-20-oxosteroids.88 Schiff bases afford oxaziranes on treatment with peracids.285 By means... 

Substitution at the cyclopropane ring is also observed when diazocyclopropane reacts with d -20-oxosteroids. ° From pregna-4,16-diene-3,20-dione the major product (25%) was the corresponding dihydro[17a,16-c]pyrazole 3 which, however, reacted further to a significant extent and gave 4 (19%) and 5 (3%). When 3/J-acetoxypregna-5,16-dien-20-one was exposed to diazocyclopropane under the same conditions two products resulted the main product 6 was isolated in 64% yield, but in addition 7 was obtained in 15% yield. The latter product results when 6 is attacked by the diazo compound at the carbonyl group. 

A 2.4-fold excess of trimethyloxosulfonium iodide stirred 45 min. with the same excess of NaOH in dimethyl sulfoxide to produce dimethyloxosulfonium methylid, the startg. 17-chloro-20-oxosteroid added, stirred 1.5 hrs. at 40°, and the crude product acetylated during 16 hrs. with acetic anhydride-pyridine 3) -acetoxy-16a-methylspiro[androst-5-en-17,l -cyclobutan]-3 -one. Y 55%. R. Wiechert, Ang. Ch. 82, 219 (1970). 

A number of fluorinated steroids can be determined by adaptation of the flask-combustion method in addition to their determination through the 17,21-dihydroxy-20-oxosteroid moiety (see p. 593). 

The intramolecular alkylation of 20-oxosteroids with 16-tosyl groups (102) has been useful in the formation of ring D in the total syntheses of cortisone and aldosterone (Schemes 65, 70, and 104). The initial product of this reaction is the 17 -compound (103), which is readily isomerized into the 17/3 -isomer (104), which is more stable with a trans-linkage of rings C and D. 

Brooks, C.J. W. and Harvey, D.J. (1970), Gas chromatographic and mass spectrometric studies of oximes derived from 20-oxosteroids. Steroids, 15,283. 

Oxosteroids (17-ketosteroids) [1, 2] e.g. dihydroxyandrosterone, androsterone, aetiocholanolone, 11-oxoandrosterone... 

Oxosteroids produce blue-black chromatogram zones on colorless to pale yellow backgrounds. 

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... 

A ketene intermediate is also proposed in the following photolysis of the oxosteroid(38) ... 

Oxosteroids, oxo bile acids 5-Dimethylaminonaphthalene-l -sulfonyl hydrazine 82, 83... 

Liu S, Sjovall J, Griffiths WJ. 2000. Analysis of oxosteroids by nano-electrospray mass spectrometry of their oximes. Rapid Commun Mass Spectrom 14 390-400. 

This enzyme [EC 1.1.1.146] catalyzes the reaction of an 11/3-hydroxysteroid with NADP+ to produce an 11-oxosteroid and NADPH. 

Walker, B. R, Connacher, A. A., Lindsay R. M., Webb, D. J., Edwards, C. R. (1995) Car-benoxolone increases hepatic insulin sensitivity in man a novel role for 11-oxosteroid reductase in enhancing glucocorticoid receptor activation. J Clin Endocrinol Metab 80, 3155-3159. 

Johnson substitutes trifluoroacetic acid (TFA) for acetic acid and conducts the de-rivatization at 75 C. Griffiths et al. [22] also report extensively on Girard hydrazone derivatives applied to LC-MS analysis of oxosteroids. 

Griffiths WJ, Alvelius G, Liu S, Sjovall J (2004) High-energy collision-induced dissociation of oxosteroids derivatised to Girard hydrazones. Eur J Mass Spectrom (Chichester, Eng) 10 63-88... 

Higashi T, Yamauchi A, Shimada (2005b) 2-Hydrazino-l-methylpyridine a highly sensitive derivatization reagent for oxosteroids in liquid chromatography-electrospray ionization-mass spectrometry. J Chromatogr 825 214-222... 

Lemonde HA, Custard EJ, Bouquet J, Duran M, Overmars H, Scambler PJ, Clayton PT (2003) Mutations in SRD5B1 (AKR1D1), the gene encoding delta(4)-3-oxosteroid 5)8-reductase, in hepatitis and liver failure in infancy. Gut 52 1494-1499... 

Palermo M, Marazzi MS, Hughes BA, Stewart PM, Shackleton CHL (2008) Human A4-3-oxosteroid 5(3-reductase (AKR1D1) deficiency and steroid metabolism. Steroids 2008 73 417-23... 

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. 

Asymmetric reduction of 25-24-oxosteroids. Reduction of the unsaturated 24-oxosteroid 2 with LiAlH, and the (R)-( + )-isomer of Noyori s reagent (1) gives a mixture of the two diols 3 and 4 in the ratio 95 5. The stereoselectivity is reversed by use of (SM )-l. This reaction was used to prepare optically pure (24R)- and (24S)-24-hydroxycholcstcrol and the epimeric pairs of 24,25-dihydroxycholesterol and 25,26-dihydroxycholcsterol.2... 

Enzymatic isomerization of ds-aconitate to trans-aeon itate apparently also involves proton abstraction,165 with resonance in the anion extending into the carboxylic acid group. Its mechanism may be directly related to that of the oxosteroid isomerase. However, there are other 1,3-proton shifts in which neither a carbonyl nor a carboxyl group is present in the substrate (Eqs. 13-55,13-56). 

Oxophenarsine 597s 5-Oxoproline, 551s, 662s Oxosteroid isomerase 526, 696 molecular activity 696 A5-3-Oxosteroid isomerase... 

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