Steroidal compounds not occurring naturally

Boldenone (17 -boldenone) is an androgenic steroid with known anabolic properties. As the oxidation of 17-ol to 17-one steroids is a recurring pathway both in vivo and in vitro, boldenone studies in cattle liver microsomes performed in vitro showed that the most prominent metabolite formed was androst-l,4-diene-3,17-dione 111). Not long ago, it was assumed drat the presence of boldenone or its main metabolite in the urine implied illegal administration of this steroid to the animal. Evidence has been recently presented that the presence of only the boldenone metabolite in urine cannot be taken as a proof of the illegal use of tills compound because boldenone is a naturally occurring steroid in urine of cattle (12). Nevertheless, the presence of 17 -boldenone in urine at levels above 

1-2 g/L seems to be clear proof of its illegal use, although clear cut-off levels have not been yet assessed. 

Chlormadinone acetate is a synthetic progestagen used to prevent or suppress ovulation. Injection of chlormadinone acetate intramuscularly at a level of 200 mg in the neck of a veal calf results in relatively high residue concentrations in the urine of the treated animal (13). Levels of chlormadinone acetate residues in the urine of calves were found to range between 6 and 18 ppm. 

Chlortestosterone is a steroid that is biotransformed in cattle to various metabolites. Urine analysis showed that the major metabolites were represented by the compounds 4-chlorandrost-4-ene-3,17-dione, 4-chlorandrost-4-ene-3, 17 -diol, and 4-chlorandrost-4-ene-3-ol-17-one (14). 

In sheep treated intravaginally with medroxyprogesterone acetate, residues were highest and more persistent in fat lower residue levels were found in liver and muscle. Mean residue concentrations in fat were higher than 20 ppb at 2 h posttreatment, declining to 14 ppb at 2 days and to approximately 7.5 ppb at 5 days posttreatment. Residues in liver and muscle were 2 ppb at 2 h and 1 ppb at 2 days posttreatment, respectively, declining to less than 1 ppb at 5 days posttreatment. In kidney, residue levels were less than 1 ppb at all time points. 

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Fig. 7.2 Chemical structures of commonly used steroidal compounds not occurring naturally.

P-Hydroxy steroids which contain the 5,7-diene system and can be activated with uv light to produce vitamin D compounds are called provitamins. The two most important provitamins are ergosterol (1) and 7-dehydrocholesterol (3). They are produced in plants and animals, respectively, and 7-dehydrocholesterol is produced synthetically on a commercial scale. Small amounts of hydroxylated detivatives of the provitamins have been synthesized in efforts to prepare the metaboHtes of vitamin D, but these products do not occur naturally. The provitamins do not possess physiological activities, with the exception that provitamin D is found in the skin of animals and acts as a precursor to vitamin D, and synthetic dihydroxalated... 

The rings are conventionally lettered and numbered as indicated above. However, in actual conformation the basic structure of steroid is not planar. It has also been observed that in the naturally occurring steroidal compounds the substitutions in the rings usually occm at C-3, C-7 and C-11 positions. 

The multiples of isoprene units in a terpene serve to classify it Cio, monoterpenes C15, sesquiterpenes C20, diterpenes C30, tri-terpenes to which the steroids are closely related C25, sesterpenes. It is a curious thing to note that the isoprene rule, sound and powerfully useful not least for structure elucidation, has unnatural foundations. Isoprene (4.1) is not a naturally occurring compound. Instead the clay from which the terpenes are so orderly fashioned is isopentenyl pyrophosphate (4.14) and dimethylallyl pyrophosphate (4.15). The latter is seen in many natural compounds, e.g. (4.11) as a prenyl ... 

Although animals produce steroids, the low concentrations of these compounds does not make these commercially (nor ethically) attractive sources of these substances. Furthermore, they could only serve as sources of naturally occurring steroids. Thus we would not have selected this option. 

This chapter covers only the chiral compounds that are cited in the literature by virtue of their optical activity. To keep the chapter to an acceptable length, a discussion of the stereochemical properties of sulfenamides showing axial chirality is omitted (17). Similarly, to limit the scope of the review, the chemistry of penicillin, cephalosporin sulfoxides and related compounds (14,18,19), steroidal sulfoxides (15,16), and other naturally occurring chiral sulfur compounds (4) is not discussed. For the same reason, only selected results are discussed and in some cases only references are given to recent papers and review articles on special topics. 

However, corticosteroids and their metabolites (1) were early recognized as possessing powerful antiinflammatory and immunomodulatory properties. Even prior to 1950, reports of the antiarthritic properties of cortisone (1) by Hench and co-workers (2) indicated the potential for these compounds to reduce the suffering of patients with inflammatory diseases. This awareness, combined with the first synthesis of naturally occurring glucocorticoids (11-desoxycorticosterone), led not only to the massive increase in research in the area of steroid synthesis and physiology, but to a Nobel prize in 1950 for early steroid pioneers Hench, Reichstein, and Kendall. 

Vitamins. The vitamins are natural organic compounds of considerable diversity that occur widely. The name derives from the Latin vita (life) and amin, a shortened form of amine. The name reflects the historical discovery of these substances, not all of which are amines. They are all of relatively low molecular weight, especially compared to peptides but in a range comparable to steroids. These substances are uniformly active and play various roles in biosynthesis and metabolism. The vitamins are too numerous to detail here but the most common examples are illustrated. They are classed using the common system, that is, water or fat soluble, depending on their approximate level of hydrophobicity or hydrophilicity. Their names are typically nonsystematic but the diversity of their structures requires that the trivial names be used. 

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