Testosterone chemistry

Methods have been reported for the conversion of jervine into C-nor-D-homo-steroids that are functionalized at C-18.57-58 The key intermediate, aldehyde (27a), was prepared from 11-deoxojervine (25a) via the hexahydro-derivative (26a), as summarized in Scheme l.57 Alternatively, JV,0-diacetyl-ll-deoxojer-vine (25b) was reduced sequentially with Pt/H2 and with Rh/Pt/H2 and the product (26b) was converted into the aldehyde (27b) by irradiation of a solution of (26b) in benzene, in the presence of mercuric oxide and iodine.58 Further studies have been reported on the chemistry of C-nor-D-homo-steroids that are derived from jervine.59 Details of the formal conversion of jervine into testosterone have been published.60... 

Today, many of the older methods used historically in clinical chemistry are being replaced by methods that utilize MS. In 2013, some areas of interest in clinical chemistry include steroid and vitamin D analyses that require a high selectivity and relative sensitivity. For example, the improved selectivity is essential in the analysis of testosterone in infants due to low concentrations. Immunoassays are not sufficiently selective to provide an accurate measurement of the true concentrations of these metabolites. There are many more assays being used or that are now in development in clinical chemistry, but a discussion of this growing use of metabolic screening is too broad and too evolutionary to be included here. Therefore, this chapter focuses on those proteins and metabolites (e.g., amino acids and acylcamitines) that are part of a classic newborn screening panel. 

Butenandt shared the 1939 chemistry prize for his sex hormone work), and Laqueur is generally credited with being the first to purify testosterone in 1935. [8]... 

Smith S. Free testosterone. Endocrinology and metabolism in-service training and continuing education. Vol. 11. Washington, DC American Association for Clinical Chemistry, 1993 59-62. 

The patient was otherwise very healthy. She reported no other health problems, a review of her body systems showed no abnormalities, and she was rarely ill. Blood samples were taken at the first appointment, and her blood counts and blood chemistry were normal. The levels of follicle-stimulating hormone and luteinizing hormone were in normal ranges, but the serum testosterone was significantly elevated. Follow-up ultrasonography revealed several small cysts on each ovary, confirming the diagnosis of polycystic ovary disease. 

The results of pelvic examination and blood chemistry tests were entirely normal. The levels of follicle-stimulating hormone and luteinizing hormone were normal, while serum testosterone was elevated. Pelvic ultrasonography revealed multiple cysts on each ovary. 

They are not excessively used in medicinal chemistry. Divinyl oxide is an excellent general anesthetic but it polymerizes easily and forms peroxides. Stabilization of the compound is usually achieved by addition of 0.01% of Ai-phenyl a-naphtylamine. On the other hand, compounds such as kainic acid, vinylbital, quinine, 17a-vinyl-testosterone, compound SKF 100 047, and vigabatrin (Figure 20.16) are perfectly stable vinyl derivatives. 

At present, this suggested nucleus of methods and equipment seems to be the optimum mix for a small steroid division within a routine department of clinical chemistry. A further step into GLC or doubleisotope methods should be taken only if an addition to the group of at least one professional and two technicians is contemplated. This holds independently of capital cost. A reasonable range of GLC methods needs the full-time service of at least this number of staff. Even then, this step should be taken with caution and after a careful assessment of the real return. Thus if we consider the, by and large, excellent electron-cap-ture-GLC method of van der Molen and Groen (V2), the two extra technicians could achieve 40 determinations of plasma testosterone and progesterone per week. (No time allowed for technical backup work.) The same two technicians using Johansson s rapid modification (J4)... 

Orally administered testosterone, and also derivatives that feamre a secondary hydroxyl group at C17, are rapidly deactivated in the liver. These agents, as a result, never attain therapeutically effective blood levels. This rapid inactivation can be avoided by adding an alkyl group at that position. The chemistry used for such additions generates a 17)8 -hydroxyl analogous to that present in testosterone. Much of the research on androstanes has as a result been focused on molecules that possess an alkyl group at Cn that substituent is most commonly methyl. 

Testosterone is a male sex hormone, one of a class of compounds known as androgens. Included in this group are testosterone, dihydrotestosterone, and androstenedione. Androgens are synthesized from cholesterol and are considered steroid hormones, a category of hormones that includes female sex hormones such as estrogen. The isolation and synthesis of testosterone were reported in 1935. Chemists Adolf Butenandt and Leopold Ruzicka later received the Nobel Prize in chemistry (in 1939) for this work and related discoveries. 

A new selective method of oxidizing alcohols was found by Pfitzner and Moffat.425 Treating primary or secondary alcohols with 2-5 moles of dicyclo-hexycarbodiimide (or related compounds such as diisopropylcarbodiimide) in anhydrous dimethyl sulfoxide containing 0.1-2 moles of H3P04 leads to aldehydes or ketones. The phosphoric acid can be replaced by pyridinium phosphite, cyanoacetate, hydrochloride, sulfate, or even phosphate the dimethyl sulfoxide may be diluted with 9 times its volume of an inert solvent. The reaction is carried out at 20° and sometimes gives superlative yields it is recommended particularly for steroid chemistry testosterone gives, e.g., 92% of 4-androstene-3,17-dione by this method. 

The reaction involves three steps and has been the subject of considerable mechanistic interest (Figure 10.15). Androstanedione is converted to estrone, testosterone to 17 3-estradiol, and 16-hydroxy DHEA to estriol. The first two steps are relatively straightforward, for example, RCHj RCHjOH —> CHO (at Cl9). The third step was difficult to rationalize with classic FeO " chemistry, and there has been general acceptance of a FeOO -based mechanism originally developed by Robinson and Akhtar, and further developed in models by Coon and Vaz. ... 

In the 1930s, however, interest in the compound was revived. In 1935, scientists obtained the first pure sample from testosterone and were able to confirm Brown-Sequard s findings. Within a matter of years, the compound became especially popular among middle-aged men who believed that it could restore their physical and mental abilities. Testosterone was first synthesized in 1935 by German chemist Adolf Friedrich Johann Butenandt (1903-1995), an accomplishment for which he was awarded the 1939 Nobel Prize in Chemistry. 

Considered in the historical context, the timing of Mamoli s pioneerii application of microbial methods to the organic chemistry of steroids was logical. Just a few years earlier the correct structure of the steroid nucleus had been established. In 1935 testosterone was isolated from steer testis by Laqueur and was shown to be a powerful male hormone in a variety of animal tests. The structure was established by Butenandt and Ruzicka during the same year. The possibility of important medical... 

Aguilera R, Chapman TE, Starcevic B, Hatton CK, and Catlin DH (2001) Performance characteristics of a carbon isotope ratio method for detecting doping with testosterone based on urine diols Controls and athletes with elevated testosterone/epitestosterone ratios. Clinical Chemistry 47 292-300. 

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