Dehydroepiandrosterone structure

Chemical Name 3 5-Hydroxyandrost-5-en-17-one heptanoate Common Name Dehydroepiandrosterone enanthate Prasterone enanthate Structural Formula ... 

The intermediates employed in the biosynthesis of androgens belong to two structurally different chemical classes, a,)3-unsaturated ketones (progesterone) and /3,y-unsatui ated alcohols (pregnenolone and dehydroepiandrosterone). The biosynthetic pathways in the production of androgens are also different [390]. 

I) Consider three structurally similar Cis steroids —testosterone, an-drostenedione, and dehydroepiandrosterone. Each of these compounds is secreted into the blood stream by glands, and after provoking its biochemical effect, is metabolized and excreted. If the only source of the plasma pool were provided by the glandular secretion of the hormone, then the secretion rate would be used to calculate the plasma concentration. However, the picture in the case of the three Ci steroids is complicated by the fact that the three compounds are peripherally interconvertible. Since both glandular secretion and peripheral conversion of precursors contribute to the plasma pool, the production rate is used to... 

Variations in lattice energies between amorphous and crystalline forms can significantly influence a drug s aqueous solubility, and increases of several hundredfold were observed for morphine and benzimidazole derivatives. Furthermore, a substance may exist in more than one crystalline form, such as chloramphenicol, dehydroepiandrosterone (DHEA), progesterone, sul-fathiazole, carbamazepine, cortisone, or prednisolone, to name a few. Polymorphic transformations, routinely observed for pharmaceuticals, are structural differences resulting from different crystal arrangements of molecules in the solid state. Although thermodynamic differences between polymorphs disappear once dissolved. 

In most mammals, estrogens (female sex steroid hormones) are synthesized from cholesterol using the parent ring structure, cyclopentanoperhydrophenan-threne of the estrane series. The steroidogenic pathway includes the production of the androgenic precursors dehydroepiandrosterone and androstenedione, the latter of which is converted to testosterone, then to estradiol-17/i. This requires aromatization of these andogenic precursors by an aromatase enzyme complex. The major source of estrogen in postmenopausal women is the conversion of androstenedione to estrone by aromatase activity... 

It is common to find multiple solid forms of a single organic compound. For example, the androgen dehydroepiandrosterone (DHEA, Fig. 30) exists in at least seven solid forms. Three polymorphic forms, three hydrates, and a methanol solvate were made and characterized (40). Single-crystal structure determinations were carried out on forms I, SI, S3, and S4 (41,42). Structural features of the various forms are compared in Table 10 and Fig. 31. 

MR Caira, JK Guillory, L-C Chang. Crystal and molecular structures of three modifications of the androgen dehydroepiandrosterone (DHEA). J Chem Crystallogr 25 393, 1995. 

Androgens, the male sex hormones, proved far more elusive that either the estrogens and progestins since they occur at much lower concentrations in biological fluids. The bioassay used to track the isolation in this case comprised the capon unit . This was the amount of extract that produced a 20% increase in the surface of a rooster s comb. The 15 mg of pure crystalline testosterone isolated in 1931 came from about 15 0001 of urine. The structural investigations of this series relied on the then newly discovered side chain oxidations of cholestanol (13-1) (Scheme 1.13). This method in essence comprised fairly drastic oxidation of reduced cholesterols of known stereochemistry at the A-B junction to afford in fairly low yield products in which the side chain at Cn had been consumed to leave behind a carbonyl group. One of these products proved to be identical with androsterone (13-2). That compound had in turn been obtained from a sequence of reactions starting from dehydroepiandrosterone (13-3) that had been isolated from male urine. 

F. 34.23. Synthesis of the steroid hormones. The rings of the precursor, cholesterol, are lettered. Dihydrotestosterone is produced from testosterone by reduction of the carbon-carbon double bond in ring A. Structural changes between the precursor and final hormone are noted in blue. DHEA = dehydroepiandrosterone. The dashed lines indicate alternative pathways to the major pathways indicated. The starred enzymes are those that may be defective in the condition congenital adrenal hyperplasia. 

The discovery of oestrone (VII) in 1929 by Doisy and independently by Butenandt was followed in 1934 by the isolation of progesterone (II) from corpus luteum tissue and of dehydroepiandrosterone (IV) from urine (see review by Petrow [16]). Although their chemical structures were not fully elucidated, a relationship between them and cholesterol was assumed. 

Ap-57 Okada, M., and Saito, Y., Steroids 6, 651 (1965). Assignment of structure to 7a, ISa-dihydroxylated product from Gibberella saubinetti on dehydroepiandrosterone. 

A modification of the Pettenkofer reaction has been devised by Munson et al. (92) and Hansen (59) and applied to the estimation in urinary extracts of dehydroepiandrosterone and compounds with similar structures in rings A and B. This procedure depends upon the development of absorption centering at 660 m/i when dehydroepiandrosterone is treated with furfural in a mixture of acetic and sulfuric acids. The specificity of this reaction appears to be limited essentially to A -3j3-stenols, A -androstadien-17-one, A -3/3-chloroandrostene-17-one, and probably 3,5-cycloandrostan-olone. Procedures for the estimation of dehydroepiandrosterone and similar compounds by treatment with sulfuric acid and alcohol have also been reported by Patterson (96), Allen et al. (1), Dirscherl (35-37), and Jensen (63-65). 

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