Steroids, review

Somatotropin, the P-adrenergic agonists, and the anaboHc steroids are considered metaboHsm modifiers because these compounds alter protein, Hpid, carbohydrate, mineral metaboHsm, or combinations of these and they partition nutrient use toward greater rates of protein deposition, ie, muscle growth, and lesser rates of Hpid accretion. Historical data leading to understanding of the mechanism (s) of action are found in reviews on anaboHc steroids (1), somatotropin (2—4), and the phenethano1 amines (5—7). 

Classification of the anabolic steroids is based on chemical stmctures and associated actions. A review of the biosynthesis and metabolism of the naturally occurring estrogens and androgens is available (1). Names, descriptions, approval dates, and recommended doses of the commercial products are found in References 1, 8, and 9. Although steroids may be orally active, the FDA approved mode of adrninistration is the subcutaneous implant. Effective dose is lower with implant rather than oral adrninistration. 

Quantitative Structure—Activity Relationships. Many quantitative stmcture—activity relationship (QSAR) studies of progestins have appeared in the Hterature and an extensive review of this work is available (174). QSAR studies attempt to correlate electronic, steric, and/or hydrophobic properties to progestational activity or receptor binding affinity. A review focusing on the problems associated with QSAR of steroids has been pubUshed (175). 

The area of nonsteroidal antiestrogens along with other classes of nonsteroidal antagonists of sex-steroid hormone action has been reviewed to 1986, and these compounds have been grouped by chemical stmcture as a basis of classification rather than any biochemical or biological test system utilized to assess antagonist activity (46). 

Experimental procedures have been described in which the desired reactions have been carried out either by whole microbial cells or by enzymes (1—3). These involve carbohydrates (qv) (4,5) steroids (qv), sterols, and bile acids (6—11) nonsteroid cycHc compounds (12) ahcycHc and alkane hydroxylations (13—16) alkaloids (7,17,18) various pharmaceuticals (qv) (19—21), including antibiotics (19—24) and miscellaneous natural products (25—27). Reviews of the microbial oxidation of aUphatic and aromatic hydrocarbons (qv) (28), monoterpenes (29,30), pesticides (qv) (31,32), lignin (qv) (33,34), flavors and fragrances (35), and other organic molecules (8,12,36,37) have been pubflshed (see Enzyp applications, industrial Enzyt s in organic synthesis Elavors AND spices). 

A spectacular example of selective deliydiogenation in the steroid ring system (42) has been attributed to stereoelectronic effects (31) the yield is 80%. Several related steroids also show this chemistry. An extensive review containing many additional examples and a mechanistic discussion is available (23). 

Cardiac steroids occur ia small amounts ia various plants with a wide geographical distribution. The purple foxglove Di talispurpurus has been used for centuries as both a dmg and a poison. Isolation and characterization of the various cardiac steroids have been reviewed (122,123). 

The stereocontroUed syntheses of steroid side chains for ecdysone, cmstecdysone, brassinoHde, withanoHde, and vitamin D have been reviewed (185). Also, other manuscripts, including reviews on the partial synthesis of steroids (186), steroid dmgs (187—189), biologically active steroids (190), heterocychc steroids (191), vitamin D (192), novel oxidations of steroids (193), and template-directed functionali2ation of steroids (194), have been pubhshed. 

Data collected on the uv spectra of steroids are available in several books, spectmm adases, and review articles (263). The most characteristic absorptions in steroid hormones include a,P-unsaturated ketones, conjugated dienes, and phenoHc A-rings (264). 

Generally, the most powerful method for stmctural elucidation of steroids is nuclear magnetic resonance (nmr) spectroscopy. There are several classical reviews on the one-dimensional (1-D) proton H-nmr spectroscopy of steroids (267). C-nmr, a technique used to observe individual carbons, is used for stmcture elucidation of steroids. In addition, C-nmr is used for biosynthesis experiments with C-enriched precursors (268). The availability of higher magnetic field instmments coupled with the arrival of 1-D and two-dimensional (2-D) techniques such as DEPT, COSY, NOESY, 2-D J-resolved, HOHAHA, etc, have provided powerful new tools for the stmctural elucidation of complex natural products including steroids (269). 

Implantable controlled release dmg deUvery systems, including Norplant and other contraceptive steroids ia siUcone-based devices, have been reviewed (91,92). 

CI(L)109) Similar to reviews (2) and (3) above, but more concerned with steroidal rearrangements. 

Use of DMF as a solvent for the oxidation of l-o1efins has been reported by Clement and Selwitz. The method requires only a catalytic amount of PdCl2 and gives satisfactory yields under mild conditions. A small amount of olefin migration product is the only noticeable contaminant in the cases reported. The procedure can be applied satisfactorily to various 1-olefins with other functional groups. This useful synthetic method for the preparation of methyl ketones has been applied extensively in the syntheses of natural products such as steroids,macrolides, dihydrojasmone, and muscone. " A comprehensive review article on the palladium-catalyzed oxidation of olefins has... 

I. For a historical review of this reaction, see L. Fieser and M. Fieser, Steroids, Reinhold, New York, 1959, Chapter 4. 

Catalytic hydrogenation has been utilized extensively in steroid research, and the method has been found to be of great value for the selective and stereospecific reduction of various functional groups. A number of empirical correlations concerning selectivity and product stereochemistry compiled for steroid hydrogenations has been listed in a previous review. ... 

Site-specific deuterium labeling of steroids can also be accomplished by biosynthetic procedures, using deuterated precursors, but these methods are beyond the scope of this chapter. For reviews of this subject see, for example, ref. 45, 54 and 55. 

The oxidizing properties of positive halogen precursors have been reviewed by Filler. Compounds which have been used in steroid hydroxyl oxidations are Wbromosuccinimide Wbromoacetamide (NBA), A-bro-... 

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