571-36-8Relevant articles and documents
Discovery of a novel hybrid from finasteride and epristeride as 5α-reductase inhibitor
Yao, Zhiyi,Xu, Yingjun,Zhang, Minmin,Jiang, Sheng,Nicklaus, Marc C.,Liao, Chenzhong
, p. 475 - 478 (2011)
Finasteride and epristeride both inhibit 5α-reductase with high potency via competitive and non-competitive mechanism, respectively. A new hybrid of finasteride and epristeride was designed as a new 5α-reductase inhibitor based on combination principles in medicinal chemistry. Human 5β-reductase was chosen as a plausible surrogate of 5α-reductase type II and the results indicate that although the hybrid compound possesses the main bulk of epristeride, its inhibitory mechanism is same as of finasteride. The hybrid turned out to be a potent 5α-reductase inhibitor in low IC 50 ranges.
Temperature effects on the catalytic activity of the D38E mutant of 3-Oxo-Δ5-steroid isomerase: Favorable enthalpies and entropies of activation relative to the nonenzymatic reaction catalyzed by acetate ion
Houck, Wendy J.,Pollack, Ralph M.
, p. 16416 - 16425 (2004)
3-Oxo-Δ5-steroid isomerase (ketosteroid isomerase, KSI) catalyzes the isomerization of 5-androstene-3,17-dione (1) to 4-androstene-3,17-dione (3) via a dienolate intermediate (2-). KSI catalyzes this conversion about 13 orders of magnitude faster than the corresponding reaction catalyzed by acetate ion, a difference in activation energy (ΔG?) of ～18 kcal/mol. To evaluate whether the decrease in ΔG? by KSI is due to enthalpic or entropic effects, the activation parameters for the isomerization of 1 catalyzed by the D38E mutant of KSI were determined. A linear Arrhenius plot of k cat/KM versus 1/T gives the activation enthalpy (ΔH? = 5.9 kcal/mol) and activation entropy (TΔS? = -2.6 kcal/mol). Relative to catalysis by acetate, D38E reduces ΔH? by ～10 kcal/mol and increases TΔS? by ～5 kcal/mol. The activation parameters for the microscopic rate constants for D38E catalysis were also determined and compared to those for the acetate ion-catalyzed reaction. Enthalpic stabilization of 2- and favorable entropic effects in both chemical transition states by D38E result in an overall energetically more favorable enzymatic reaction relative to that catalyzed by acetate ion.
Silver-catalyzed vinylogous fluorination of vinyl diazoacetates
Qin, Changming,Davies, Huw M. L.
, p. 6152 - 6154 (2013)
A silver-catalyzed vinylogous fluorination of vinyl diazoacetates to generate γ-fluoro-α,β-unsaturated carbonyls is presented. Application of this method to the fluorination of farnesol and steroid derivatives was achieved.
Activation enthalpies and entropies for the microscopic rate constants of acetate-catalyzed isomerization of 5-androstene-3,17-dione
Houck, Wendy J.,Pollack, Ralph M.
, p. 10206 - 10212 (2003)
Both acetic acid and acetate catalyze the isomerization of 5-androstene-3,17-dione (1) to its conjugated isomer, 4-androstene-3,17-dione (3), through a dienol(ate) intermediate. The temperature dependence of the overall isomerization rate constants and of the microscopic rate constants for this isomerization was determined, and the Arrhenius plots give the activation enthalpy and entropy for each step. The source of the activation energy for the overall isomerization and for each of the individual steps is predominantly enthalpic, with a moderate to low entropic penalty. Additionally, the entropy and enthalpy for the keto - enol equilibrium of 1 and dienol were determined; this equilibrium is entirely controlled by enthalpy with no entropic contribution. The relevance of these results to the mechanism of the isomerization of 1 catalyzed by the enzyme 3-oxo-Δ5-steroid isomerase is discussed.
Selective oxidation of steroidal homoallylic alcohols using pyridinium chlorochromate (PCC)
Parish,Luo,Parish,Heidepriem
, p. 2839 - 2847 (1992)
Pyridinium chlorochromate (PCC), in the presence of anhydrous calcium carbonate, has been found to be an effective and convenient reagent for the selective oxidation of steroidal homoallylic alcohols to the corresponding β,δ-unsaturated ketones in good yield.
Method for preparing 4-androstenedione from dehydroepiandrosterone acetate
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Paragraph 0026; 0031; 0032; 0037; 0038; 0043, (2019/07/04)
The invention provides a method for preparing 4-androstenedione from dehydroepiandrosterone acetate. The method comprises the following steps: carrying out a hydrolysis reaction on dehydroepiandrosterone acetate to obtain dehydroepiandrosterone, carrying out an oxidation reaction on the dehydroepiandrosterone to obtain crude 4-androstenedione, adding methanol and dichloroethane to the crude 4-androstenedione, and performing purification to obtain refined 4-androstenedione, wherein the obtained refined 4-androstenedione can be further reacted with potassium tert-butoxide to obtain 5-androstenedione. The method for preparing 4-androstenedione from dehydroepiandrosterone acetate has the following advantages: the preparation process is simple and feasible, and the production rate is improved,so the production values of enterprises are improved; and the cheap dehydroepiandrosterone acetate is used as the raw material to prepare the 4-androstenedione greatly demanded on the market, and the4-androstenedione is reacted to further prepare the 5-androstenedione, so the production cost of the enterprise is saved.
Development of a Chemoenzymatic Process for Dehydroepiandrosterone Acetate Synthesis
Fryszkowska, Anna,Peterson, Justine,Davies, Nichola L.,Dewar, Colin,Evans, George,Bycroft, Matthew,Triggs, Neil,Fleming, Toni,Gorantla, Srikanth Sarat Chandra,Hoge, Garrett,Quirmbach, Michael,Timmanna, Upadhya,Reddy Poreddy, Srinivas,Kumar Reddy, D. Naresh,Dahanukar, Vilas,Holt-Tiffin, Karen E.
, p. 1520 - 1528 (2016/08/30)
Dehydroepiandrosterone (DHEA, 2) is an important endogenous steroid hormone in mammals used in the treatment of a variety of dysfunctions in female and male health,1 as well as an intermediate in the synthesis of steroidal drugs, such as abiraterone acetate which is used for the treatment of prostate cancer.2-4 In this manuscript we describe a novel, concise, and cost-efficient route toward DHEA (2) and DHEA acetate (3) from 4-androstene-3,17-dione (4-AD, 1). Crucial to success was the identification of a ketoreductase from Sphingomonas wittichii for the highly regio- and stereoselective reduction of the C3-carbonyl group of 5-androstene-3,17-dione (5) to the required 3β-alcohol (2, >99% de). The enzyme displayed excellent robustness and solvent stability under high substrate concentrations (up to 150 g/L).
Characterization of hamster NAD+-dependent 3(17)β-hydroxysteroid dehydrogenase belonging to the aldo-keto reductase 1C subfamily
Endo, Satoshi,Noda, Misato,Ikari, Akira,Tatematsu, Kenjiro,El-Kabbani, Ossama,Hara, Akira,Kitade, Yukio,Matsunaga, Toshiyuki
, p. 425 - 434 (2015/11/27)
The cDNAs for morphine 6-dehydrogenase (AKR1C34) and its homologous aldo-keto reductase (AKR1C35) were cloned from golden hamster liver, and their enzymatic properties and tissue distribution were compared. AKR1C34 and AKR1C35 similarly oxidized various xenobiotic alicyclic alcohols using NAD+, but differed in their substrate specificity for hydroxysteroids and inhibitor sensitivity. While AKR1C34 showed 3α/17β/20α-hydroxysteroid dehydrogenase activities, AKR1C35 efficiently oxidized various 3β- and 17β-hydroxysteroids, including biologically active 3β-hydroxy-5α/β-dihydro-C19/C21-steroids, dehydroepiandrosterone and 17β-estradiol. AKR1C35 also differed from AKR1C34 in its high sensitivity to flavonoids, which inhibited competitively with respect to 17β-estradiol (Ki 0.11-0.69 μM). The mRNA for AKR1C35 was expressed liver-specific in male hamsters and ubiquitously in female hamsters, whereas the expression of the mRNA for AKR1C34 displayed opposite sexual dimorphism. Because AKR1C35 is the first 3(17)β-hydroxysteroid dehydrogenase in the AKR superfamily, we also investigated the molecular determinants for the 3β-hydroxysteroid dehydrogenase activity by replacement of Val54 and Cys310 in AKR1C35 with the corresponding residues in AKR1C34, Ala and Phe, respectively. The mutation of Val54Ala, but not Cys310Phe, significantly impaired this activity, suggesting that Val54 plays a critical role in recognition of the steroidal substrate.
PROCESSES FOR THE PREPARATION OF DEHYDROEPIANDROSTERONE AND ITS INTERMEDIATES
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Page/Page column 19; 20, (2014/12/12)
The present application relates to a regioselective and stereoselective processes for the preparation of dehydroepiandrosterone (DHEA) and processes for its intermediates.
Convenient method for the functionalization of the 4- and 6-positions of the androgen skeleton
Morton, Daniel,Dick, Allison R.,Ghosh, Debashis,Davies, Huw M. L.
, p. 5838 - 5840 (2012/07/14)
The preparation and reactivity of steroidal vinyldiazo compounds is reported, providing a convenient, substituent tolerant, chemo- and stereoselective entry into 4- and 6-substituted androgen analogues from a common precursor. Under dirhodium catalysis, O-H insertion occurs at the carbenoid site, leading to 4-substituted steroids, but under silver catalysis, O-H insertion occurs at the vinylogous position, leading to 6-substituted steroids.
