Corticosteroids esters

Transamination of barbiturate derivatives with semicarbazide Hydrolysis and acyl migration of corticosteroid esters Rate enhancement by CTABr depends on substrate structure Substrate micellization inhibits hydrolysis and acyl migration Reddy and Katiyar, 1981 Anderson el ai, 1983... 

Like in Chapt. 7, we begin the discussion with acetates, since acetic acid is the simplest nontoxic acyl group, formic acid being less innocuous. An informative study was carried out to compare the kinetics of hydrolysis of two types of corticosteroid esters, namely methyl steroid-21-oates (which are active per se) and acetyl steroid-21-ols (which are prodrugs), as exemplified by methyl prednisolonate (8.69) and prednisolone-21-acetate (8.70), respectively [89]. In the presence of rat liver microsomes, the rate of hydrolytic inactivation of methyl steroid-21-oates was much slower than the rate of hydrolytic activation of acetyl steroid-21-ols. Thus, while the Km values were ca. 0.1 -0.3 mM for all substrates, the acetic acid ester prodrugs and the methyl ester drugs had Vmax values of ca. 20 and 0.15 nmol min-1 mg-1, respectively. It can be postulated that the observed rates of hydrolysis were determined by the acyl moiety, in other words by the liberation of the carboxylic acid from the acyl-enzyme intermediate (see Chapt. 3). 

Melby, J. C. and M. St. Cyr. 1961. Comparative studies on absorption and metabolic disposal of water-soluble corticosteroid ester letabolisml 0 75-82. 

Fleisher, D., et al. 1986. Oral absorption of 21-corticosteroid esters A function of aqueous stability and intestinal enzyme activity and distribution. J Pharm Sci 75 934. 

Under the usual reaction conditions, the corticosteroid C21-esters do not react at all with periodic acid but they do oxidize after alkaline hydrolysis. The possibility exists therefore of finding a selective difference CD method for the determination of this class of corticosteroid esters. 

All is not lost however because the periodic acid method is found to be quantitative for the determination of corticosteroid esters, if these are first hydrolysed using a quaternary base, e.g. tetramethylammonium hydroxide. The acidic products formed in the above side-reaction do not perturb the determination, since the optically active product of the periodate oxidation following the hydrolysis is similar to the etianic acid. 

The CD method selectively measures the quantity of corticosteroid ester in the presence of 21-hydroxycorticosteroids, as the latter are oxidized in both the unknown and the comparative solution. 

D.G. Watson, A.G. Davidson, B.I. Knight, The analysis of some corticosteroids and corticosteroid esters by LC-frit-FAB-AdS, Rapid Commun. Mass Spectrom., 11 (1997)415. 

FI. Faires, J. S., and McCarty, D. P., Jr., Acute synovitis in normal joints of man and dog produced by injection of microcrystalline sodium urate, calcium oxalate and corticosteroid esters. Arthritis Rheumat. 6, 295-296 (1962). 

The introduction of a 9(11) double bond into steroids is of practical interest, since such olefins can be converted to the 9-fluoro-l 1 -hydroxy grouping found in most useful corticosteroids. Ester 6 had a benzophenone-4-hexanoic acid tethered to the hydroxyl group of androstan-17/3-ol that curled under the steroid ring and photochemically inserted into the C-9 a-hydrogen, forming product 7 with a 9(11) double bond after lead tetraacetate cleavage of the carbinol product and hydrolytic cleavage of the tether (Scheme 6-3) [33]. A product with a 14,15 double bond was also produced. 

Steroids represent another typical class of doping substances. The determination of endogenous steroids (e.g., testosterone), synthetic anabolic steroids, their esters and their conjugates, and corticosteroids by HPLC-MS has been recently object of an exhaustive review [115] and will not be further discussed here. 

Esters of corticosteroids can also be determined. Studies with cortisone acetate showed that hydrolysis of the ester is a prerequisite to the reaction with a tetrazolium salt [83],... 

Cyclooxygenase-1 and -2 expression in rheumatoid synovial tissues. Effects of interleukin-1 beta, phorbol ester, and corticosteroids, J. Clin. Invest. 1994, 93, 1095-1101. 

Furoic acid (furan-2-carboxylic acid, or pyromucic acid) is used as a bactericide, and the furoate esters are used as flavoring agents, as antibiotic and corticosteroid intermediates. It is obtained by the enzymatic or chemical/catalytic aerobial oxidation of furfural (2-furalaldehyde) the latter is the only unsaturated large-volume organic chemical prepared from carbohydrates today. D-Xylose and L-ara-binose, the pentoses contained in the xylan-rich portion of hemicelluloses from agricultural and forestry wastes, under the conditions used for hydrolysis undergo dehydration to furfural. 

Anderson, B. D., R. A. Conradi, and K. E. Knuth. 1985. Strategies in the design of solution-stable, water-soluble prodrugs. I. Aphysical-organic approach to pro-moiety selection for 21 -esters of corticosteroids. J. Pharm. Sci74 365-374. 

Flynn, G L. and D. J. Lamb. 1970. Factors in uencing solvolysis of corticosteroid-21-phosphate esters. J. Pharm. Sci59 1433-1438. 

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