Steroids Related to Progesterone

The lack of oral activity of progesterone proper has already been mentioned. Even after the orally active 19-nor agents, which showed progestational activity, had been elaborated, the search continued for an orally active compound that contained the full pregnane nucleus (115). At the time such a compound would have had the economic advantage of sidestepping the then burdensome ring A aromatization reactions. 

In a modification of this scheme, hydroxypregnenolone is first acetylated under mild conditions to the 3-acetate and then under forcing conditions with caproic anhydride to give the acetate-caproate (122). Ester interchange with methanol removes the acetate at 3 Oppenauer oxidation affords hydroxyprogesterone caproate (124).  

Introduction of a substituent at the 6 position serves, as we have seen in the case of dimethisterone, to increase markedly the potency of progestins. In the first of these efforts, ricetoxyprogesterone, an agent known to have oral activity, was the molecule so modified. Treatment of hydroxyprogesterone 

17 double bond of 6-methyl-16-dehydropregnenolone acetate by means of lithium in liquid ammonia leads initially to the 17 enolate ion, 152 this is alkylated in situ with methyl iodide. The now-familiar steric control asserts itself to afford the 17a- 

It should be noted that the stereochemistry of the B/C and C/D junctions has remained inviolate in all the modifications discussed to date. It was in fact assumed that changing either of these was a quick path to loss of activity. Just such a modification, however, led to a progestin with a unique pharmacologic profile. 

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STEROIDS PART 2 COMPOUNDS RELATED TO PROGESTERONE, CORTISONE, AND CHOLESTEROL... 

A stereoselective synthesis of aminoalkyl-substituted P-lactams (41) has been developed, the key step of which is [2+2] cycloaddition of imines to ketenes generated photochemically from diazoketones (42), which are derived from protected a-amino acids. A number of steroidal diazoketones related to progesterone have been synthesized as potential photoaffinity labelling reagents for the mineralocorticoid receptor. ... 

The steroids we will consider as targets for synthesis are shown here (Steroids-1). Cholesterol (and derivatives) is an important component of cell membranes. Gallstones are mainly cholesterol. It is one of the steroids most familiar to the layperson. Other steroids of much interest include the sex hormones (structurally related to progesterone) and the corticosteroids, represented here by cortisone. 

The neuroactive steroids or neurosteroids are a class of steroids structurally related to progesterone, which have anaesthetic properties. " In fact progesterone itself was shown to have anaesthetic and sedative properties in the... 

Recently, Voogt et al. [91] have reported on the d5-pathway in steroid metabolism of Asterias rubens. These workers established the existence of the d5-pathway (Scheme 20), analogous to the pathway found in mammals this conclusion was based on the observation that radiolabeled cholesterol (1) was converted to pregnenolone (112), 17a-hydroxypregnenolone (141), and androstenediol (142). Labeled pregnenolone was converted additionally to progesterone (129). Androstenediol (142) was the main metabolite of de-hydroepiandrosterone (143), a reaction catalyzed by 17/i-hydroxysteroid dehydrogenase (17/1-HSD). The metabolic conversion of androstenedione (131) to testosterone (132) is also mediated by 17/J-HSD and is related to... 

The first behavioral observations related to these steroids date back to Se-lye, who over 50 years ago reported that progesterone and deoxycorticosterone... 

Druids harvested the mistletoe berry yearly and used it in their winter celebrations, known as samain and imbolc, which were centered on the winter solstice. For this celebration, the Druids concocted a strong potion of the berries, which researchers have subsequently discovered contains a female-like steroid that may have stimulated the libido (presumably structurally related to either estrogen or progesterone). Mistletoe has, of course, become a contemporary symbol to Yuletide merrymakers as a license to kiss. 

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