Pregnenolone Acetate Research Articles

Synthesis of 3/gb-acetoxy-24-norchola-5,20(22)-dien-23-al. a new intermediate for an improved synthesis of [24- 14c]-cholesterol

[24- 14C]-Cholesterol was synthesized by reaction between the phosphorane derivative of [1- 14C]-isobutyltriphenylphosphonium bromide and 3β-acetoxy-24-norchola-5,20(22)-dien-23-al (IX) followed by hydrogenation of the condensation product. The intermediate IX was prepared by two different procedures both starting from pregnenolone acetate.

Reaktionen mit polyvalenten jodverbindungen—II : Zur bildung von C 6H 5J(Cl)(N 3) und dessen verhalten gegenüber olefinen

It is possible to transform phenyliodoso diacetate (C 6H 5I(OAc) 2) by stepwise substitution involving (CH 3) 3SiN 3 and CH 3COCl into phenyliodosochloride-azide C 6H 5I(Cl)(N 3). The reactions of this reagent are very different in respect to those of ClN 3. While the stereoisomeric compounds 1 and 2 are formed by treating phenylcyclohexene-1 with ClN 3, the title reagent yields the stereoisomeric mixture 4. The product 8 results by reaction of camphene with ClN 3, whereas with C 6H 5I(Cl)(N 3) product 10 is obtained. Benzonorbornene reacts with both, ClN 3 and C 6H 5I(Cl)(N 3), yielding the same compound 5 (7-antichlor-5- exo-azido-benzonorbornane). The reaction of C 6H 5I(Cl)(N 3) with cholesteryl acetate proceeds by “ cis”-addition of Cl and N 3 forming 5α-chloro-6α-azido-3β-acetoxycholestane 15. ClN 3 does not yield any cis-addition product. C 6H 5I(Cl)(N 3) reacts with the double bond of androstenolone acetate and pregnenolone acetate not only in “ cis” but also in “ trans” addition manner, yielding 19, 21, 23 and 25. In addition to the encountered chloro-azido compounds the corresponding dichlorides are formed.

Synthesis of campesteryl acetate ((24 R)-24-methyl-3β-acetoxycholesten-5-ene) and its 24 S-epimer

A synthesis of campesteryl acetate and its 24 S epimer has been accomplished starting from the optically active 3,4-dimethylpentylmagnesium bromides and pregnenolone acetate. The two epimers have different utilization by the larvae of Dermestes maculatus.

The synthesis and stereochemistry of (22 R)-20α,22- and (22 S)-20α,22-dihydroxycholesterol

An improved synthesis of (22 R)-20α,22- and (22 S)-20α,22-dihydroxycholesterol from pregnenolone acetate is described and the stereochemistry at C-20 and C-22 established. The title compounds have been labeled at C-1 and C-2, using 20α-hydroxycholesta-1,4-diene-3,22-dione as starting material.

Tumor localizing agents V. Radioiodinated pregnanes

Previous studies with progesterone-4-14C suggested that a radioiodinated analog might be useful for photoscanning the adrenal gland and associated tumors. 21-Iodoprogesterone was prepared by conversion of deoxycorticosterone to its mesylate and subsequent displacement with iodide. Depending on the conditions for mesylation, 21-chloroprogesterone could also be isolated. 21-Iodopregnenolone acetate was obtained in a similar manner from the 21-bromo analog which in turn was prepared in good yield from the enol acetate of pregnenolone acetate. The radioiodinated steroids were prepared by isotope exchange with sodium iodide-125 in refluxing acetone. Tissue distribution studies showed that the radioactivity concentrated mainly in the thyroid gland presumably as a result of rapid in vivo deiodination.

Location of hydroxy groups introduced to steroid molecules by adrenal and testicular enzymes. I

Incorporation of molecular oxygen into steroids by hydroxylases from adrenal and testicular glands was demonstrated by using 18O 2 as the tracer for molecular oxygen, and analyzing the hydroxylated products by a special mass-spectrometric technique. Methods for determining the definite position and form of oxygen atoms thus incorporated were proposed. After confirmation of 18O atom incorporation into the products, the presence of the 18O atom was examined in the fragments which were found on mass spectrometry. 17α-Hydroxyprogesterone, which was produced from progesterone under 18O 2 by microsomal enzymes of testis, was found to retain the 18O atom in the form of a 17α-hydroxy group, since the dehydrated fragment of 17α-hydroxyprogesterone was devoid of 18O. Testosterone produced from progesterone under the same conditions was found to retain the 18O atom in the 17β-hydroxy group, since the fragment which lost a CH 2CO group in the A ring of testosterone acetate retained the 18O atom. The pregnenolone acetate which was produced from 20α, 22 R-dihydroxycholesterol under 18O 2 by adrenal enzymes, contained no 18O in the form of the 20-ketone of pregnenolone, since the fragment which was produced by removal of the 3β-acetoxy group as acetic acid was devoid of 18O. The hydroxylated steroid was also chemically degraded, and the degradation product was further analyzed mass-spectrometrically to locate the 18O atom in the molecule. Deoxycorticosterone and 11-deoxycortisol were produced from progesterone and 17α-hydroxyprogesterone, respectively, by adrenal homogenate under 18O 2 and were found to have incorporated 18O. These corticoids were then chemically degraded to remove parts of the side-chains, and the degradation products were found to be devoid of 18O. This suggests that the 18O atoms were incorporated in the form of a 21-hydroxy group.

3-BETA-HYDROXYSTEROID DEHYDROGENASE ACTIVITY IN THE MOUSE OVARY.

SUMMARY Sections of ovaries from 30 Swiss white mice were incubated with ten steroid substrates to demonstrate 3β-hydroxysteroid dehydrogenase activity histochemically. The substrates were: (1) 3β-hydroxypregn-5-en-20-one (pregnenolone), (2) 3β,17α-dihydroxypregn-5-en-20-one (17α-hydroxypregnenolone), (3) 3β-hydroxyandrost-5-en-17-one (DHA), (4) 3β,17β-dihydroxyandrost-5-ene (androstenediol), (5) 3β-sulphoxypregn-5-en-20-one (pregnenolone sulphate), (6) 3β-sulphoxy-17α-hydroxypregn-5-en-20-one (17α-hydroxypregnenolone sulphate), (7) 3β-sulphoxyandrost-5-en-17-one (DHA sulphate), (8) 3β-acetoxypregn-5-en-20-one (pregnenolone acetate), (9) 3β-acetoxyandrost-5-en-17-one (DHA acetate), and (10) 3β-acetoxy-17β-hydroxyandrost-5-ene (androstenediol acetate). Pregnenolone, 17α-hydroxypregnenolone, DHA and androstenediol gave a colour reaction in the corpora lutea, interstitial tissue, theca interna and stroma of all ovaries examined. The granulosa of many follicles, some thought to be atretic, also contained diformazan granules. 17α-Hydroxypregnenolone did not give as intense a reaction as the other free steroids. No diformazan was deposited with DHA sulphate as substrate. Pregnenolone sulphate and 17α-hydroxypregnenolone sulphate were used by the same tissues as were the free steroids, although they were much less well utilized. Utilization of 3β-acetoxy derivatives was similar to that of the free steroids.

3-BETA-HYDROXYSTEROID DEHYDROGENASE IN THE ADRENAL GLAND AND PLACENTA.

SUMMARY 3β-Hydroxysteroid dehydrogenase activity was studied histochemically in human, monkey, and rat adrenal glands and in human placentae. Tissue sections were incubated separately with each of the following substrates: (1) 3β-hydroxypregn-5-en-20-one (pregnenolone); (2) sodium 3β-sulphoxypregn-5-en-20-one (pregnenolonesulphate); (3) 3β-acetoxypregn-5-en-20 one (pregnenoloneacetate); (4) 3β,16α-dihydroxypregn-5-en-20-one (16α-hydroxypregnenolone); (5) 3β,17α-dihydroxypregn-5-en-20-one (17α-hydroxypregnenolone); (6) ammonium 3β-sulphoxy-17α-hydroxypregn-5-en-20-one (17α-hydroxypregnenolone ammonium sulphate); (7) 3β-hydroxyandrost-5-en-17-one (DHA); (8) 3β-sulphoxyandrost-5-en-17-one (DHA sulphate); (9) 3β-acetoxyandrost-5-en-17-one (DHA acetate); (10) androst-5-ene-3β, 17β-diol (androstenediol). The histochemical results obtained with pregnenolone and DHA as substrates resemble those described by other workers. Using pregnenolone sulphate and 17α-hydroxypregnenolone sulphate, a strong histochemical reaction with diformazan deposition was found in the zona fasciculata of the adrenals of all species and in the placental syntrophoblast. With DHA sulphate an extremely weak histochemical reaction was obtained with the adrenal zona fasciculata, monoformazan only being deposited. The syntrophoblast, however, showed intense 3β-hydroxysteroid dehydrogenase activity when incubated with DHA sulphate. These results accord with recent findings regarding the secretion and metabolism of 3β-sulphoxysteroids. A strong histochemical reaction was also obtained in both adrenal and placental tissues using 17α-hydroxypregnenolone, 16α-hydroxypregnenolone, androstenediol, pregnenolone acetate, and DHA acetate. These steroids have not previously been described as substrates for the histochemical demonstration of 3β-hydroxysteroid dehydrogenase in the adrenal or placenta.

STEROIDS AND RELATED PRODUCTS: XXI. THE SYNTHESIS OF 17α-BROMO-6α -METHYLPROGESTERONE

The synthesis fo 17α-bromo-6α-methylprogesterone, from pregnenolone acetate, is reported. The product is a potent luteoid with marked oral activity. In the course of this investigation, a useful variation of the synthesis of 6α-methylprogesterone, from pregnenolone, was devised. The rearrangement of a 5β,6β-epoxide to a 6-ketone, upon chromatography on aluminum oxide "Woelm", was observed.

STEROIDS AND RELATED PRODUCTS: XIII. THE SYNTHESIS OF 6α-FLUORO-17α-BROMOPROGESTERONE

The synthesis of 6α-fluoro-17α-bromoprogesterone, a new potent gestogen, from pregnenolone acetate, is reported.

Syntheses of Hormones from 5,6-Dichloro Steroids. I. Addition of Chlorine to Pregnenolone Acetate

Syntheses of Hormones from 5,6-Dichloro Steroids. I. Addition of Chlorine to Pregnenolone Acetate

STEROIDS AND RELATED PRODUCTS: X. 17α-BROMOPROGESTERONE, A NEW POTENT GESTOGEN

The synthesis of a new derivative of progesterone, 17α-bromoprogesterone, from pregnenolone acetate, is reported. The product was found to be a potent gestogen in contradistinction to its isomer, 21-bromoprogesterone.

STEROIDS AND RELATED PRODUCTS: X. 17α-BROMOPROGESTERONE, A NEW POTENT GESTOGEN

The synthesis of a new derivative of progesterone, 17α-bromoprogesterone, from pregnenolone acetate, is reported. The product was found to be a potent gestogen in contradistinction to its isomer, 21-bromoprogesterone.

Combined therapy in histoplasmosis and coccidioidomycosis; methyltestosterone and meth-dia-mer-sulfonamides.

THERE IS no reported instance of treatment of systemic fungous disease in man with testosterone compounds. In 1953 Lamb and his associates 1 reported the cure of a mycetoma caused by an atypical Nocardia under treatment with large doses of pregnenolone acetate. Trial of this steroid in disseminated coccidioidomycosis has been unsuccessful. * The use of aromatic diamidines structurally related to synthetic estrogens is being thoroughly investigated by Curtis and his co-workers. 2 The present paper presents in vitro and in vivo laboratory studies of testosterone compounds as fungistatic agents and a report of the clinical trial of methyltestosterone and meth-dia-mer-sulfonamides (triple sulfonamides) in three cases of the deep mycoses. LABORATORY ASSAY OF ANTIMYCOTIC EFFECT OF TESTOSTERONE COMPOUNDS AND SULFONAMIDES In Vitro Assay of Testosterone, Methyltestosterone, and Testosterone Propionate .—In 1949 Reiss 3 demonstrated that testosterone, methyltestosterone, and other steroids and steroid-like compounds possess moderate fungistatic activity in vitro against Histoplasma capsulatum and other pathogenic fungi. Using a pour

Pregnenolone acetate in treatment of mycetoma (nocardiosis).

THE PURPOSES of this presentation are (1) to report a case of mycetoma (nocardiosis) in a child who had failed to respond to all the standard forms of therapy and who apparently has been cured by treatment with pregnenolone acetate and (2) to call attention to pregnenolone acetate as an agent free from undesirable metabolic or toxic effects, which has useful antifungal properties that warrant further clinical investigation. BACKGROUND With the increased interest in antifungal medicaments, many new approaches are under investigation. The Streptomyces group of Actinomycetes have yielded many new antibiotics which show some antifungal properties, such as acti-dione,® from Streptomyces griseus. Other Streptomycetes may yield less toxic and more potent fungicides. The ideal antifungal drug would be one which could be used both locally and orally, which would diffuse through sweat, the nail bases, and the sebum of the hair follicles and which would thus

A comparative study of pregnenolone, 21-acetoxypregnenolone and ACTH.

THE evaluation of new drugs in the treatment of rheumatoid arthritis and spondylitis has become a grave responsibility of the medical profession. Since the scarcity of ACTH and cortisone, as well as their limitations and side-effects, is now generally known, favorable recommendations of new drugs based on clinical experience are likely to cause unrest and new hopes among those suffering from disabling rheumatic disease. Certain drugs that have been the object of recent clinical studies and subsequent publicity are steroids of the pregnenolone, pregnenolone acetate, 21-acetoxypregnenolone and pregnenolone diacetate group (also known by various brand names such as prenone, artisone . . .

A Note on the Solubility of Pregnenolone and Pregnenolone Acetate in Various Solvents

A Note on the Solubility of Pregnenolone and Pregnenolone Acetate in Various Solvents

The quantitative determination of pregnenolone and pregnenolone acetate by infrared spectrophotometry

An infrared spectrophotometric method is described for the quantitative determination of pregnenolone and its acetate in pharmaceutical preparations. Optical density measurements are made at several intense absorption peaks, and the concentration is calculated independently from each measurement. The agreement between the different measurements is an indication of the presence or absence of impurities.