A’-Pregnenolone

Fig. 2. Biosynthesis of testosterone (a) Pregnenolone (b) 17-hydroxy pregneno-line (c) dehydrois-oandrosterone (d) progesterone (e) 17-hydroxypro ges terone If androstenedione (g) testosterone...

Fig. 5. Pattern of product formation during single turnover cycles of anaerobic reduction/oxygenation of the cytochrome P-450,.,. - cholesterol - adrenodoxin complex. The results are expressed as a percentage conversion of the total [14C]cholesterol added to the incubation. Cholesterol, o 22-hydroxy-cholesterol, 20,22-dihydroxycholesterol. a pregnenolone, (from Ref. 38, with permission).

Acetoxy-l-nonanoic add, 811 N-Acetoxyphthalimide, 9 21-Acetoxypregnane-3,ll,20-trione, 524 17a-Acetoxy-A -pregnene-3d-ol-20-one, 318 17a-Acetoxy-A -pregnenolone formate, 36-... 

Fig. 2. A typical 20 X 20 cm thia-layer chromatography plate for the assay of the following compounds in infant urine A, pregnenolone B, DHA C, unknown D, 21-OH-pregnenolone E, androstenediol F, 16-oxo-androstenediol G, 16a-OH-DHA H, 16,8-OH-DHA I, 16a-OH-pregnenolone. The position of androstenetriol (not assayed) is shown at J. Samples of 16a-OH-DHA were run in positions 1 (1J25 gg), B (3.75 /xg), and 7 (5.0 /xg). Samples (2A jig) of all the steroids measured (except for the unknown and 16/8-OH-DHA) were run in position S. Duplicate extracts of urines collected from the same baby on days 1, 2, 3, 4, 5, and 6 of life were run in positions 4, 6, 8, 9, and 10. The plate was sprayed with antimony trichloride then heated. From Shackleton and Mitchell (S9).

DL DiPietro, RD Brown, CA Strott. A pregnenolone radioimmunoassay utilizing a new fractionation technique for sheep antiserum. J Clin Endocrinol Metab 35 729, 1972. 

Aminoglutethamide (Cytadren) Blocks conversion of cholesterol to A -pregnenolone (the first step in steroid synthesis). Uses Cushing s disease adjunct to irradiation in preparino patients for adrenalectomy treatment of adrenal, breast, and ACTH-producing tumors. 

Pregnenolone (88) is dehydrogenated by DDQ in refluxing dioxane. The reaction proceeds via the intermediates (89) and (90). This procedure is from a general description lacking specific details. ... 

The addition of HF to the 5,6-double bond in 3-hydroxy-A -steroids has been investigated intensively. Bowers et al. prepared the 5oc-fluoro derivative (32) from pregnenolone acetate (31) in 10 % yield using methylene dichloride-THF as solvent at 0°. Pregnenolone itself is converted in 30%... 

In the early 1930 s, when the prime research aim was the commercial synthesis of the sex hormones (whose structures had just been elucidated), the principal raw material available was cholesterol extracted from the spinal cord or brain of cattle or from sheep wool grease. This sterol (as its 3-acetate 5,6-dibromide) was subjected to a rather drastic chromic acid oxidation, which produced a variety of acidic, ketonic and hydroxylated products derived mainly by attack on the alkyl side-chain. The principal ketonic material, 3j -hydroxyandrost-5-en-17-one, was obtained in yields of only about 7% another useful ketone, 3 -hydroxypregn-5-en-20-one (pregnenolone) was obtained in much lower yield. The chief acidic product was 3j -hydroxy-androst-5-ene-17j -carboxylic acid. All three of these materials were then further converted by various chemical transformations into steroid hormones and synthetic analogs ... 

Overall yields of 37% from pregnenolone acetate to 19-norprogesterone and of 43% from 3 -acetoxy-5a-chloro-6l5-hydroxy androstan-17-one to A io)-19-norandrostene-3,17-dioneii have been reported using 6)5,19-ethers as key intermediates. 

Ozonization of A -steroids usually gives complex mixtures (however, see ref. 48). Ozonolysis became a practical step in the general synthesis of B-norsteroids with the discovery that added methanol" (or formaldehyde ) improves yields significantly. Thus, Tanabe and Morisawa prepared 5/ -hydroxy-6/ -formyl-B-norsteroids (74) from cholesterol acetate, dehydroepiandrosterone acetate and pregnenolone acetate in overall yields of 64-74% by the reaction sequence represented below. 

FIGURE 25.43 The steroid hormones are synthesized from cholesterol, with intermediate formation of pregnenolone and progesterone. Testosterone, the principal male sex hormone steroid, is a precursor to /3-estradiol. Cortisol, a glucocorticoid, and aldosterone, a mineralocorticoid, are also derived from progesterone. 

Pregnenolone is transported from the mitochondria to the ER, where a hydroxyl oxidation and migration of the double bond yield progesterone. Pregnenolone synthesis in the adrenal cortex is activated by adrenocorticotropic hormone (ACTH), a peptide of 39 amino acid residues secreted by the anterior pituitary gland. 

Allylic bromination of pregnenolone acetate with dibromodi-methylhydantoin affords the 7-bromo compound (155) of undefined stereochemistry. Dehydrobromination by means of collidine followed by saponification affords the 5,7 endocyclic cis,cis-diene, 156. This compound contains the same chromophore as ergosterol, a steroid used as a vitamin D precursor. The latter displays a complex series of photochemical reactions among the known products is lumisterol, in which the stereochemistry at both C9 and Cio is inverted. Indeed, irradiation of 156 proceeds to give just such a product (158). This reaction can be rationalized by... 

Deletion of the 17a-hydroxy group similarly leads to an effective topical antiinflammatory agent. Treatment of 16a-methylpregnenolone (244) (obtained by conjugate addition of an organometallic to pregnenolone) sequentially with bromine and acetate ion affords the 21 acetate, 245 (see, for example, the transformation of 196 to 198). In an interesting variation on the method for the introduction of a fluorine atom at 6, the... 

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