Progestin synthesis

The 1950s and 1960s saw the development of orally active progestins based on the synthesis of steroids that lack the C19-angular methyl substituent (19-norsteroids). The commercial production of these compounds for the regulation of menstmal disorders began in 1957, and for oral contraception in 1960. 

Interest in the synthesis of 19-norsteroids as orally active progestins prompted efforts to remove the C19 angular methyl substituent of readily available steroid precursors. Industrial applications include the direct conversion of androsta-l,4-diene-3,17-dione [897-06-3] (92) to estrone [53-16-7] (26) by thermolysis in mineral oil at about 500°C (136), and reductive elimination of the angular methyl group of the 17-ketal of the dione [2398-63-2] (93) with lithium biphenyl radical anion to form the 17-ketal of estrone [900-83-4] (94) (137). 

Progesterone is synthesized in the corpus luteum in a cycle timed to the menstrual cycle. Synthesis continues should pregnancy develop. Progestins such as megestrol acetate and medroxyprogesterone acetate find use in therapy for metastatic breast cancer. 

Regardless of their source of synthesis, glucocorticoids, mineralocorticoids, androgens, estrogens, and progestins exert their effects on the brain through... 

The synthesis of the progestin antagonist onapristone (31-2) also starts with the saponification product from (24-2). In this case, the intermediate is first converted to a 3,3-drmethylpropylene acetal by reaction with neopentyl glycol oxidation as... 

Therapeutic indications for the progestational drugs based on pregnanes described above are rather limited. This is particularly true when compared to the reduced estrane-based nor compounds that are used in oral contraceptives. This circumstance, combined with the availability of the half-dozen or so C-19 progestins, posed as a disincentive to further research on the synthesis of new compounds. This is reflected in the pubhcation dates of reports on the synthesis of these compounds. 

In the animal body three important groups of hormones are formed by the metabolism of cholesterol the progestins, the sex hormones, and the adrenal cortical hormones 249 Their synthesis occurs principally in mitochondria of the adrenal cortex and the gonads. Steroid hormone synthesis is regulated by hormones, such as corticotropin (ACTH), from the anterior pituitary250 (see Chapter 30) and is also dependent upon the recently discovered steroidogenic acute regulatory protein, which in some way promotes the movement of stored cholesterol into mitochondrial membranes.251 252 Some major pathways of... 

Representative Partial Syntheses. The synthesis of 19-nnr-stcroids was stimulated by the development of orally active progestins as birth control agents. 

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