Progesterone transformation products

An important transformation in steroid biochemistry is the conversion of pregnenolone into progesterone. Progesterone is a female sex hormone, a progestogen, but this reaction is also involved in the production of corticosteroids such as hydrocortisone and aldosterone. The reaction also occurs in plants, and features in the formation of cardioactive glycosides, such as digitoxin in foxglove. 

In every case the information provided has been obtained by collating public domain sources of information, but unfortunately very often little data is available, particularly on commercial aspects, even for products that have proved to be big successes. Thus microbial biotransformations for steroid modification, particularly stereoselective hydroxylations, such as the use of Rhizopus arrhizus to convert progesterone into antiinflammatory and other dmgs via 11- -hydroxyprogestrone, have proved to be very successful. However, comparatively little useful information exists from public domain sources, despite (or perhaps because) a market of hundreds of millions /a exists for such microbially transformed steroids (cortisone, aldosterone, prednisolone and prednisone etc.) produced by microbial hydroxylation and dehydrogenation reactions coupled with complimentary chemical steps. 

Both LH and FSH are referred to as gonadotropins, beoause they aot on the male and female gonads, which results in the production of the sex steroids testosterone and estradiol, respectively. In the female, FSH and LH act in concert in regulating ovarian function egg maturation, ovulation, and transformation of the ruptured follicle into the corpus luteum. In males, spermatogenesis is dependent on these two hormones. Specifically, FSH in females facilitates the maturation of ovarian folliole oells and their secretion of estradiol, whereas in males, it stimulates the maturation of sperm in the testes. In females, LH promotes ovulation, formation of the oorpus luteum, and progesterone secretion in males, it enables the secretion of testosterone from the testes. 

The synthesis of lanosterol (140) from epoxide 139 has an Lfo, =+4. The key multiple ring-closure step 141+142- [143] in Johnson s synthesis of progesterone has also an Lfoj =+4 (Lfor for [143]- 144 would depend on the by-products). Next, we see the three steps 145+146- 147- [148]- 149 in Vollhardts synthesis of estrone with Lfor is +3, -1, +2 respectively for the overall transformatiom L r =+3-l+2=+4. The next two transformations, ISO- 151 in Nicolaou s biomimetic synthesis of endiandric acid A, and Negishi s palladium-catalyzed tetracyclization 152- 153 are also characterized by Lfor =+4. Trost s one-step polyclization... 

Steroids are animal hormones. However, their potential as pharmaceutical products could not have been realized while their manufacture depended on methods such as the extraction of estrone (13) from the urine of pregnant mares Cholesterol (14) and bile acids were better sources, but one of the initial steps in the requisite conversion involved oxidation with chromic acid, a transformation which was not efficient. Not until Marker realized in the early 1940s that progesterone (15) and testosterone (16) could be readily synthesized from diosgenin (17), a plant steroid obtained from a... 

In this example, the A ring is preformed and the cyclization gives an A/B cis junction. The product was then readily transformed to the naturally occurring hormone, progesterone. Thus, acetylenic groups are particularly useful terminators of polycyclization. 

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