Testosterone, 11-keto

Although methylation of 3-keto-A -steroids generally leads to 4,4-dimethyl derivatives,Atwater has reported a practicable4-monoaikylation procedure. Thus 4-methyl- (44%), 4-vinyl- (46%), 4- -butyltestosterone (62%) and 4-methyl-19-nortestosterone (50%) are obtained when the alkyl halide is added dropwise with stirring to a refluxing basic solution of testosterone or 19-nortestosterone over a period of 2.5 hours. A" -3-Keto steroids are not methylated under these conditions. 

More recently, permaleic acid has been recommended as a very satisfactory reagent for the Baeyer-Villiger reaction. It reacts almost as fast as trifluoroperoxyacetic acid and does not require buffering. Unfortunately, neither of these two reagents has been used extensively on 20-keto steroids a patent claims the conversion of progesterone to testosterone acetate with trifluoroperoxyacetic acid, but a later communication describes the ready reaction of 3-keto-A" -steroids with this reagent. 

Photoketone (118) has served as the key intermediate in a relatively simple transformation of 3-keto-10/ -steroids to 3-keto-lOa-isomers without the assistance of other functional groups suitably situated next to the ring junction—a task that appears difficult to attempt by other methods. Optimal yields of (118) are achieved by catalytic hydrogenation of the unsaturated ketone (175), the photoisomer of 1-dehydrotestosterone acetate (see section III-C). In this way, a 6-step conversion of 1-dehydrotestosterone acetate (174) to IOa-testosterone acetate (127 acetate) is achieved in good yield. ° ... 

A -3-Ketosteroids, e.g. triraethylsilyl- testosterone I80°C, 20 min or 150°C, 20 min Conversion of AC3-ketosteroids or [ their trimethylsilyl or acetyl derivatives in fluorescent components, whereby the detection limits were improved by 65% for the acetates. A -3-keto- and A -3-OH-steroids also react with the same sensitivity. 

Thresholds of the olfactory receptors of male goldfish are 35 pg/ml water for the prostaglandin F2a, and 100 times less for its 15-keto-derivative. The males receptor threshold for 17,20-progesterone (from females) is a tiny fraction of 1 pg/ml water. Three grams (one teaspoonful) would provide an abovethreshold stimulus when diluted in 500 x 500 x 500 m water (Bjerselius and Olsen, 1993). In lampreys, testosterone from males attracts females at a concentration of 29 pg/ml water but urine with a testosterone concentration of 29 X 10 pg/ml is active (Adams etal., 1987). 

Higashi and coworkers [28] used 2-hydrazino-l-methylpyridine (HMP) derivatization to introduce a positively charged moiety in testosterone and dihydrotestosterone (DHT) to achieve a sensitivity improvement of 70- to 1600-fold compared to underivatized molecules in ESI. However, they found the derivative was unsuitable for di-keto steroids such as androstenedione and progesterone, so this form of derivatization is unlikely to be widely accepted. Separable syn- and anti- (E and Z) stereoisomers are formed using this derivative. Preparation is as follows a solution of 10 pg HMP in 50 pi ethanol containing 25 pg TFA was added to the steroid dissolved in 30 pi ethanol. After heating for 1 h at 60 C, the solvents can be removed and sample injected. 

Steroid hormones, especially those containing the A S-keto-chromophore group, are frequently marketed in the form of oily injections. Direct determination of the active ingredient content using the CD method is conveniently done by measuring the ellipticity of an aliquot of the injection after the very simple process of dilution with an appropriate solvent [22]. Problems that might arise in these analyses and the recommended method of examination are discussed in the case of an oily injection that contains testosterone phenylpropionate. 

Another example is illustrated in Fig. 1.3. Testosterone and epitestosterone are eluted as one peak using SE-30 as the stationary phase. By conversion of the hydroxyl group into a more bulky substituent, the slight difference in the structure is enhanced and the two epimers can be resolved. The same approach can be used for the separation of 16-and 15-keto isomers of androstan-30-ol. The initial ketones are not separated on SE-30, but after conversion into the corresponding N,N-dimethylhydrazones their separation is possible as these derivatives are eluted much more slowly than the initial compounds [3]. 

Woodward s synthesis of steroids, described in Scheme 3.1, illustrates the value of a carefully thought out general plan for a synthesis. This synthesis targeted the preparation of the tetracyclic keto aldehyde 1, which can be used as an advanced intermediate to be converted into a set of natural steroids that includes progesterone 2, deoxycorticosterone 3, androsterone 4, testosterone 5, cholesterol 6, and cortisone 7 via well-known routes. The synthetic plan for 1 required solving the following key tasks ... 

Testosterone. Introduction of Ja-methyl (S-150), la-ethyl (S-151), la-methyl 17-acetate (S-72), la-chloromethyl 17-acetate (S-74), la-bromomethyl 17-acetate (S-75), la-iodomethyl 17-acetate (S-76), 1,1-dimethyl 17-acetate (S-77), la,2a-methylene 17-acetate (S-78), la-methyl 4-chloro 17-acetate(S-79), la-methyl 7a-methyl 17-acetate (S-80), la-methyl 7/3-methyl 17-acetate (S-81), la-methyl 1 l 6-hydroxy 17-acetate (S-82), 1 a,2a-methylene 11/3-hydroxy 17-acetate (S-83), la-methyl 11-keto 17-acetate (S-84), la-methyl A 17-acetate (S-86), la-methyl A 11 -keto 17-acetate (S-88), 1 a,2a-methylene A 17-acetate... 

Ia-Methyl-A -11-ketotestosterone acetate (S-88), la-methyl-11-keto-testosterone acetate (S-84), 3,11,17-triketo-A -androstene (adrenos-terone) (S-43), and 1 l-keto-17a-methyltestosterone (S-24) all show decreased androgenic and anabolic potencies compared to the those 11-unsubstituted compound. However, introduction of a 9a-fluoro substituent into S-24 will increase both androgenic and anabolic activities to a... 

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