Androstane Derivatives Research Articles

Carbon-13 nuclear magnetic resonance spectral data of steroidal vicinal ketols and related compounds

Carbon-13 nuclear magnetic resonance spectra for 31 Sβ-hydroxy and acetoxy androstane derivatives bearing vicinal oxygenated functions at ring D with and without oxygenated functions at C-6 are reported. Relative substituent effects are discussed.

Reaction of 19-Hydroxysteroids with Diethylaminosulfur Trifluoride.

Reaction of 19-hydroxycholest-4-en-3-one (1) with diethylaminosulfur trifluoride (DAST) in acetonitrile at reflux gave 10β-fluoro-5, 1-seco-5, 19-cyclocholest-4-en-3-one (2) in 60% yield. Analogous reaction of androstane derivatives afforded the corresponding bicyclo[4.4.1] compounds 6 and 8. Under milder reaction conditions, the diethylaminosulfnate 3 was secured in 20% yield from 1.

ChemInform Abstract: Synthesis of and Reactivity Studies with 19‐Peroxide Androstenedione Derivatives: Analogues of a Proposed Aromatase Intermediate.

AbstractThe ozonolysis of the estrenediones (IV) to give the aldehyde (VI) is investigated in a series of experiments with varying reaction conditions.

ChemInform Abstract: Preparation of 3‐(β‐D‐Galactopyranosyloxy)androstane Derivatives with Unsaturated Side Chain in Position 17β.

ChemInform Abstract: Preparation of 3‐(β‐D‐Galactopyranosyloxy)androstane Derivatives with Unsaturated Side Chain in Position 17β.

ChemInform Abstract: Regioselective Synthesis of Ring A Polymethylated Steroids in the Androstane Series.

AbstractThe hitherto unknown, highly substituted androstane derivatives (VI), (X) and (XIII) are prepared in order to test their biological activity.

Preparation of 3-(β-D-galactopyranosyloxy)androstane derivatives with unsaturated side chain in position 17β

Article without abstract

Simultaneous measurements of endogenous and deuterium-labelled tracer variants of androstenedione and testosterone by capillary gas chromatography-mass spectrometry

A capillary gas chromatographic-mass spectrometric method for the simultaneous determination of androstenedione and testosterone in human plasma using [19,19,19- 2H 3]androstenedione and [19,19,19- 2H 3]testosterone as internal standards is described. For calculation of plasma androstenedione and testosterone, peak heights were measured by selected-ion monitoring of the molecular ions of the heptafluorobutyryl derivatives of androstenedione and [ 2H 3]androstenedione ( m/z 482 and 485) and of testosterone and [ 2H 3]testosterone ( m/z 680 and 683). The isotope dilution method needed no complex corrections for contributions and provides a sensitive and reliable technique with good accuracy, precision and reproducibility.

ChemInform Abstract: A Facile Approach to 20‐Isocholesterol from an Androstane Derivative.

Abstract A high-yield stereoselective synthesis of (20S)-cholest-5-en-3s-ol from 3s-(tetrahydropyran-2-yloxy)-androst-5-en-17-one via ethyl (20R)-3s-(tetrahydropyran-2-yloxy)-23, 24-bisnorchol-5-en-22-oate is described.

ChemInform Abstract: Androstane Derivatives: Synthesis of Substituted 6′H‐Androst‐2‐eno‐(3,2‐b)pyran‐6′‐ones.

AbstractDiels‐Alder reaction of the androstane derivatives (I) with dichloroketene, prepared in situ from dichloroacetyl chloride (II), and subsequent elimination of HCl produce the chloropyrones (III).

ChemInform Abstract: Synthesis of a Cardenolide, 3‐O‐Methyl Uzarigenin, with 14β‐Hydroxyandrost‐16‐ene as the Key Intermediate.

Abstract A representative cardenolide 1 was synthesized starting from 17-oxo-14α-H androstane derivative 2 , with the introduction of the hydroxy group into the position 14 prior to construction of the butenolide ring. Key steps of the synthesis involve: (1) hydroxylation of 15-ene-17-one 4 in the 14β-position with SeO 2 , (2) oxidative, intramolecular cyclopropane ring formation in malo- nate 7 , (3) regio- and stereoselective opening of the cyclopropane ring in 8 with thiophenolate anion, and (4) acid- catalyzed transformation of acetal 13 into hydroxy aldehyde 14 .

Identification of 5β-pregnane and 5β-androstane derivatives in adrenal venous and peripheral blood plasma of the female possum ( Trichosurus vulpecula)

In the possum a marked sex difference has been found in the steroids in adrenal venous plasma. Four 5β-pregnane and four 5α(β) androstane derivatives together with ten 4-ene-3-keto steroids were isolated from the adrenal venous plasma of the female and definitively identified by gas chromatography-mass spectrometry. The major reduced steroids were: 5β-pregnane-3α,17α-diol-20-one and 5β-pregnane-3α,17α,20α-triol, at concentrations of 52 ± 12 μg/100 ml and 44 ± 8 μg/100 ml mean ± SEM respectively. The concentration of cortisol was 198 ± 47 μg/100 ml. The concentration of the 2 reduced steroids in peripheral plasma were approx. 100 times less. In contrast the adrenal venous plasma of a male contained 14 steroids of which only three, found in trace amounts, were reduced. The results confirm previous in vitro observations that reduced steroids are produced by the adrenocortical special zone, which is only present in the female. The physiological significance of the presence of reduced steroids of adrenocortical origin in the circulation of the female possum is discussed.

Modulation of the GABAA receptor complex by steroids in slices of rat cuneate nucleus

1. Several derivatives of pregnane and androstane that have hypnotic properties have been investigated for their ability to potentiate responses to the GABAA receptor agonist muscimol and to reduce the effect of the non-competitive GABAA antagonist picrotoxin. 2. Depolarizing responses to muscimol in slices of rat cuneate nucleus were potentiated most potently by 3 alpha-hydroxy,5 alpha-pregnane-11,20-dione (alphaxalone), which gave half-maximal potentiation at 0.15 microM. The 5 beta isomer of alphaxalone had little effect up to 3 microM but in analogues lacking an 11-keto substituent (pregnanolones), both the 5 alpha- and 5 beta-isomers potentiated with potencies 20 and 10 times lower, respectively, than that of alphaxalone. The alpha configuration of the 3-hydroxy was essential in alphaxalone, the 3 beta-hydroxy isomer being inactive. However, there was little difference between the potencies of the 3 alpha- and 3 beta-hydroxy configurations in the pregnanolones, although the maximal effects of the 3 beta-hydroxy isomers were rather lower than those of the 3 alpha-hydroxy isomers. 3. Reductions in the effect of picrotoxin as an antagonist of muscimol were caused most potently by the 3 alpha-hydroxy pregnanolones, with a ten fold reduction in picrotoxin potency at 1 microM concentrations of these steroids. Alphaxalone and its 5 beta-isomer were about half as potent. Androsterone was about 10 times less potent and the 3 beta-hydroxy pregnanolones were ineffective. 4. This difference in the structure-activity relationships for steroidal potentiation of muscimol and reduction in picrotoxin antagonism of muscimol is reminiscent of an analogous distinction found with the barbiturates.

Photoelectron spectra, electronic structure and long-range electronic interaction in some steroids

Abstract

A Facile Approach to 20-Isocholesterol From An Androstane Derivative

Abstract A high-yield stereoselective synthesis of (20S)-cholest-5-en-3ß-ol from 3ß-(tetrahydropyran-2-yloxy)-androst-5-en-17-one via ethyl (20R)-3ß-(tetrahydropyran-2-yloxy)-23, 24-bisnorchol-5-en-22-oate is described.

Synthesis of a cardenolide, 3-O-methyl uzarigenin, with 14β-hydroxyandrost-16-ene as the key intermediate

A representative cardenolide 1 was synthesized starting from 17-oxo-14α-H androstane derivative 2 , with the introduction of the hydroxy group into the position 14 prior to construction of the butenolide ring. Key steps of the synthesis involve: (1) hydroxylation of 15-ene-17-one 4 in the 14β-position with SeO 2, (2) oxidative, intramolecular cyclopropane ring formation in malo- nate 7 , (3) regio- and stereoselective opening of the cyclopropane ring in 8 with thiophenolate anion, and (4) acid- catalyzed transformation of acetal 13 into hydroxy aldehyde 14 .

Microbial production of two new dihydroxylated androstenedione derivatives by Acremonium strictum

We found that Acremonium strictum NN106 converted 4-androstene-3, 17-dione (androstenedione) to 12 compounds. Among them, five products were isolated and found to be hydroxylated at the 11α-, 14α-, 7α, 11α-, 6β, 11α- or 6β, 14α-positions of androstenedione. 6β, 11α-Dihydroxy and 6β, 14α-dihydroxy derivatives of androstenedione have been obtained for the first time. From the time course profile of this transformation, sequential hydroxylation at the 6β-position followed by 11α- or 14α-monohydroxylation was observed. The oxidative product of the 6β, 14α-dihydroxy derivative was found to be the most potent inhibitor of human placentral aromatase.

ChemInform Abstract: Steroids and Related Studies. Part 81. Potential Azasteroidal Neuromuscular Blockers.

AbstractThe androstane derivative (V) (HS‐777) is prepared from the dione (I) as shown.

A kinetic analysis of the inhibition of human prostatic 5α-reductase by 4-hydroxyandrostenedione and related steroids

The inhibition of human prostatic 5α-reductase by androstenedione (A), 4-hydroxyandrostenedione (4-OH-A), and 4-methoxyandrostenedione (4-MeO-A) was studied. All three steroids inhibited 5α-reductase in a concentration-dependent manner. The inhibition was competitive with respect to testosterone and non-competitive with respect to NADPH, indicating that these compounds inhibit 5α-reductase by acting as alternative substrates. K j values obtained were in the range 0.21–0.3 μM (A), 1.01–2.04 μM (4-OH-A), and 10.2–28.3 μM (4-MeO-A). Thus the two derivatives of androstenedione are poor inhibitors of 5α-reductase and appear to have limited clinical potential.

Substrate specificity of partially purified UDP-glucose: nuatigenin glucosyltransferase from oat leaves

Starting from the cytosol fraction of oat leaves an enzymes catalyzing the transfer of D-glucosyl moiety from UDP-Glc to nuatigenin (22S, 25S-epoxy-furost-5-ene-3β,26-diol) has been partially purified by ammonium sulphate fractionation, acetone precipitation and gel filtration on Sephadex G-100. The specificity of this glucosyltransferase was studied using a wide range of 3-OH steroids, i.e. steroid sapogenins, sterols, steroidal alkaloids andd androstane or pregnane derivatives as sugar acceptors. The highest activity was found with nuatigenin but some other structurally-related sapogenins such as isonuatigenin, chlorogenin, diosgenin or tigogenin were also glucosylated, however, at distinctly lower rates. The enzyme could glucosylate also tomatidine and solanidine as well as some 3β-OH derivatives of androstane or pregnane such as pregnenolone, androstenolone and androstanol. Typical phytosterols were very poor acceptors (5% less of the activity as compared to nuatigenin). UDP-Glc was a much better sugar source than TDP-Glc, ADP-Glc or UDP-Gal. Our results strongly suggest that the physiological function of the enzyme is its participation in the initiation of sugar chain formation during the biosynthesis of oat saponins-avenacosides A and B.

Conversion of sterols and triterpenes by mycobacteria. II. Transformation of 7-oxygenated sterols into androstane derivatives via a 7-deoxygenation

The bioconversion of 7-oxygenated sterols by Mycobacterium aurum was studied in a preliminary investigation of the microbial conversion of wool wax. 7-Oxocholesterol was found to be transformed mainly into 3,17-dioxygenated androstane derivatives. 7ξ-Hydroxylated sterols were formed in an initial reduction step, and the C-7 hydroxyl group was then eliminated in a dehydration reaction. This was thought to take place during the isomerisation of cholest-4-en-3-one to cholest-5-en-3-one. Deuterium labelling experiments showed that this elimination proceeded faster for the C-7α isomer, although it was not stereospecific. The C-7α and C-78-hydroxy isomers were weakly interconverted via the 7-oxo derivatives. Cholest-4-en-3-one, cholest-1,4-dien-3-one and cholest-4,6-dien-3-one all lost their side chains following a hydrogenation/ dehydrogenation reaction. The resulting 3,17-dioxoandrostene or 3,17-androstadiene derivatives were mainly hydrogenated into 5α-androstane-3,17-dione and 5α-androstane-3β-ol-17-one. Elimination of the 3β-hy-droxyl groups giving cholesta-3,5-dien-7-one, and subsequent microbial degradation of the side chain was not observed to any significant extent. The convergence of the bioconversion pathways of cholesterol and the 7-oxygenated cholesterols enabled crude, partially auto-oxidised cholesterol to be used as a substrate for the production of 3,17-dioxygenated androstane derivatives by M. aurum.