846-46-8Relevant academic research and scientific papers
Thermodynamic analysis of remote substrate binding energy in 3α-hydroxysteroid dehydrogenase/carbonyl reductase catalysis
Hwang, Chi-Ching,Chang, Pei-Ru,Hsieh, Chia-Lin,Chou, Yun-Hao,Wang, Tzu-Pin
, p. 183 - 189 (2019)
The binding energy of enzyme and substrate is used to lower the activation energy for the catalytic reaction. 3α-HSD/CR uses remote binding interactions to accelerate the reaction of androsterone with NAD+. Here, we examine the enthalpic and entropic components of the remote binding energy in the 3α-HSD/CR-catalyzed reaction of NAD+ with androsterone versus the substrate analogs, 2-decalol and cyclohexanol, by analyzing the temperature-dependent kinetic parameters through steady-state kinetics. The effects of temperature on kcat/Km for 3α-HSD/CR acting on androsterone, 2-decalol, and cyclohexanol show the reactions are entropically favorable but enthalpically unfavorable. Thermodynamic analysis from the temperature-dependent values of Km and kcat shows the binding of the E-NAD+ complex with either 2-decalol or cyclohexanol to form the ternary complex is endothermic and entropy-driven, and the subsequent conversion to the transition state is both enthalpically and entropically unfavorable. Hence, solvation entropy may play an important role in the binding process through both the desolvation of the solute molecules and the release of bound water molecules from the active site into bulk solvent. As compared to the thermodynamic parameters of 3α-HSD/CR acting on cyclohexanol, the hydrophobic interaction of the B-ring of steroids with the active site of 3α-HSD/CR contributes to catalysis by increasing exclusively the entropy of activation (ΔTΔS? = 1.8 kcal/mol), while the BCD-ring of androsterone significantly lowers ΔΔH? by 10.4 kcal/mol with a slight entropic penalty of ?1.9 kcal/mol. Therefore, the remote non-reacting sites of androsterone may induce a conformational change of the substrate binding loop with an entropic cost for better interaction with the transition state to decrease the enthalpy of activation, significantly increasing catalytic efficiency.
Kinetic analysis of androstenedione 5α-reductase in epithelium and stroma of human prostate
Weisser, Heike,Krieg, Michael
, p. 589 - 594 (1997)
In the human prostate, various androgen-metabolizing enzymes are present. Among these enzymes, testosterone 5α-reductase seems to be dominant. However androstenedione is also a potential substrate of the prostatic 5α-reductase. To address the question of to what extent the reduction of androstenedione to androstanedione occurs, the present study describes in detail the kinetic characteristics (K(m) and V(max)) and possible age-dependent alterations of this enzymatic step in epithelium and stroma of the human prostate. In normal prostate (NPR), the mean K(m) (nM) and V(max) (pmol/mg protein · h) were about twofold higher in stroma (K(m) 211; V(max), 130) than in epithelium (K(m), 120; V(max), 56), whereas in the benign prostatic hyperplasia (BPH), the mean K(m) (nM; mean ± SEM) and V(max) (pmol/mg protein · h: mean ± SEM) were about sixfold higher in stroma (K(m), 688 ± 121; V(max), 415 ± 73) than in epithelium (K(m), 120 ± 10; V(max), 73 ± 8). In BPH, those differences between epithelium and stroma were highly significant (p 0.001). However, the efficiency ratios (V(max)/K(m)) of neither BPH nor NPR showed any significant differences between epithelium (NPR, 0.47; BPH, 0.62 ± 0.06) and stroma (NPR, 0.70; BPH. 0.63 ± 0.05). With respect to age-related changes, only stroma showed a significant increase of K(m) (P 0.01) and V(max) (p 0.05) with age. In summary, in both epithelium and stroma of the human prostate, a 5α-reductase converts in measurable amounts androstenedione to androstanedione. The kinetic data were, in part, different between epithelium and stroma; the reason for this difference remains unclear. In comparison to other metabolic conversions, such as testosterone to dihydrotestosterone and androstenedione to testosterone, it is unlikely that, in the human prostate, the adrenal androgen androstenedione contributes significantly to the formation of testosterone and, further, of dihydrotestosterone.
Preparation method 5α- androstane -3,17- diketone (by machine translation)
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, (2020/03/17)
The preparation method 5α - of, androstane - 333317-dione comprises the following steps: (4 -) preparing the compound, androstanone through 17-hydroxycyanidation, 3-hydroxycyanidation- 17-hydroxycyanidation of, 5,6-hydroxycyanidation to, 3-position ketal acid hydrolysis as the raw material 5α - and the method has the advantages. of low production cost, product purity. (by machine translation)
Unified Total Synthesis of Five Bufadienolides
Hagiwara, Koichi,Inoue, Masayuki,Itoh, Hiroaki,Shimizu, Shinsuke
supporting information, (2020/11/13)
We report a unified total synthesis of five bufadienolides: bufalin (1), bufogenin B (2), bufotalin (3), vulgarobufotoxin (4), and 3-(N-succinyl argininyl) bufotalin (5). After the steroidal ABCD ring 8 was produced, the D ring was cross-coupled with a 2-pyrone moiety and stereoselectively epoxidized to generate 6. TMSOTf promoted a stereospecific 1,2-hydride shift from 6 to establish the β-oriented 2-pyrone of 19. Functional group manipulations from 19 furnished 1-5, which potently inhibited cancer cell growth.
A sodium trifluoromethanesulfinate-mediated photocatalytic strategy for aerobic oxidation of alcohols
Zhu, Xianjin,Liu, Can,Liu, Yong,Yang, Haijun,Fu, Hua
, p. 12443 - 12446 (2020/10/30)
A sodium trifluoromethanesulfinate-mediated photocatalytic strategy for the aerobic oxidation of alcohols has been developed for the first time, and the photoredox aerobic oxidation of secondary and primary alcohols provided the corresponding ketones and carboxylic acids, respectively, in high to excellent yields.
Photochemical Transformations with Iodine Azide after Release from an Ion-Exchange Resin
Dr?ger, Gerald,K?sel, Teresa,Kirschning, Andreas,Schulz, G?ran
supporting information, p. 12376 - 12380 (2020/05/08)
This report discloses the photochemical homolytic cleavage of iodine azide after its formation following release from polymer-bound bisazido iodate(I) anions. A series of radical reactions are reported including the 1,2-functionlization of alkenes and the unprecedented chemoselective oxidation of secondary alcohols in the presence of primary alcohols.
Catalytic Acceptorless Dehydrogenation of Aliphatic Alcohols
Fuse, Hiromu,Mitsunuma, Harunobu,Kanai, Motomu
supporting information, p. 4493 - 4499 (2020/03/05)
We developed the first acceptorless dehydrogenation of aliphatic secondary alcohols to ketones under visible light irradiation at room temperature by devising a ternary hybrid catalyst system comprising a photoredox catalyst, a thiophosphate organocatalyst, and a nickel catalyst. The reaction proceeded through three main steps: hydrogen atom transfer from the α-C-H bond of an alcohol substrate to the thiyl radical of the photo-oxidized organocatalyst, interception of the generated carbon-centered radical with a nickel catalyst, and β-hydride elimination. The reaction proceeded in high yield under mild conditions without producing side products (except H2 gas) from various alcohols, including sterically hindered alcohols, a steroid, and a pharmaceutical derivative. This catalyst system also promoted acceptorless cross-dehydrogenative esterification from aldehydes and alcohols through hemiacetal intermediates.
Microbial Modifications of Androstane and Androstene Steroids by Penicillium vinaceum
?yczko, Paulina,Panek, Anna,Swizdor, Alina
, (2020/10/02)
The biotransformation of steroid compounds is a promising, environmentally friendly route to new pharmaceuticals and hormones. One of the reaction types common in the metabolic fate of steroids is Baeyer-Villiger oxidation, which in the case of cyclic ketones, such as steroids, leads to lactones. Fungal enzymes catalyzing this reaction, Baeyer-Villiger monooxygenases (BVMOs), have been shown to possess broad substrate scope, selectivity, and catalytic performance competitive to chemical oxidation, being far more environmentally green. This study covers the biotransformation of a series of androstane steroids (epiandrosterone and androsterone) and androstene steroids (progesterone, pregnenolone, dehydroepiandrosterone, androstenedione, 19-OH-androstenedione, testosterone, and 19-nortestosterone) by the cultures of filamentous fungus Penicillium vinaceum AM110. The transformation was monitored by GC and the resulting products were identified on the basis of chromatographic and spectral data. The investigated fungus carries out effective Baeyer-Villiger oxidation of the substrates. Interestingly, introduction of the 19-OH group into androstenedione skeleton has significant inhibitory effect on the BVMO activity, as the 10-day transformation leaves half of the 19-OH-androstenedione unreacted. The metabolic fate of epiandrosterone and androsterone, the only 5α-saturated substrates among the investigated compounds, is more complicated. The transformation of these two substrates combined with time course monitoring revealed that each substrate is converted into three products, corresponding to oxidation at C-3 and C-17, with different time profiles and yields.
Chemoselective Oxidation of p-Methoxybenzyl Ethers by an Electronically Tuned Nitroxyl Radical Catalyst
Hamada, Shohei,Sugimoto, Koichi,Elboray, Elghareeb E.,Kawabata, Takeo,Furuta, Takumi
supporting information, p. 5486 - 5490 (2020/07/24)
The oxidation of p-methoxy benzyl (PMB) ethers was achieved using nitroxyl radical catalyst 1, which contains electron-withdrawing ester groups adjacent to the nitroxyl group. The oxidative deprotection of the PMB moieties on the hydroxy groups was observed upon treatment of 1 with 1 equiv of the co-oxidant phenyl iodonium bis(trifluoroacetate) (PIFA). The corresponding carbonyl compounds were obtained by treating the PMB-protected alcohols with 1 and an excess of PIFA.
Electrochemistry Broadens the Scope of Flavin Photocatalysis: Photoelectrocatalytic Oxidation of Unactivated Alcohols
Zhang, Wen,Carpenter, Keith L.,Lin, Song
supporting information, p. 409 - 417 (2019/11/25)
Riboflavin-derived photocatalysts have been extensively studied in the context of alcohol oxidation. However, to date, the scope of this catalytic methodology has been limited to benzyl alcohols. In this work, mechanistic understanding of flavin-catalyzed oxidation reactions, in either the absence or presence of thiourea as a cocatalyst, was obtained. The mechanistic insights enabled development of an electrochemically driven photochemical oxidation of primary and secondary aliphatic alcohols using a pair of flavin and dialkylthiourea catalysts. Electrochemistry makes it possible to avoid using O2 and an oxidant and generating H2O2 as a byproduct, both of which oxidatively degrade thiourea under the reaction conditions. This modification unlocks a new mechanistic pathway in which the oxidation of unactivated alcohols is achieved by thiyl radical mediated hydrogen-atom abstraction.
