- Defunctionalization of sp3 C–Heteroatom and sp3 C–C Bonds Enabled by Photoexcited Triplet Ketone Catalysts
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A general strategy for enabling a light-induced defunctionalization of sp3 C–heteroatom and sp3 C–C bonds with triplet ketone catalysts and bipyridine additives is disclosed. This protocol is characterized by its broad scope without recourse to transition metal catalysts or stoichiometric exogeneous reductants, thus offering a complementary technique for activating σ sp3 C–C(heteroatom) bonds. Preliminary mechanistic studies suggest that the presence of 2,2′-bipyridines improves the lifetime of ketyl radical intermediates.
- An, Juzeng,Gu, Yiting,Martin, Ruben,Wakeling, Matthew,Yin, Hongfei
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p. 1031 - 1036
(2022/01/19)
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- Two crystallographic forms and the absolute structure of 5α,14α-androstane
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5α,14α-Androstane (C19H32) crystallizes in two different polymorphic forms in the same vapor diffusion experiment. The major form (Form I) crystallizes as thin plates in the space group P21, with Z = 4. These plates are twinned along a long c axis of length 43?? and readily suffer from radiation damage when diffracted. The minor form (Form II) crystallizes as fine needles in the space group P212121, Z = 3. In the minor form, 5α,14α-androstane cocrystallizes with 5α,14α-androstan-17-one, an oxidation product of 5α,14α-androstane. The presence of 5α,14α-androstan-17-one in the minor form of the crystals was confirmed by HR-MS. Form II can be crystallized as a pure form without the ketone impurity using a different solvent system. High level density functional theory (DFT) lattice free energy calculations were performed and show that both pure forms are isoergic within the estimated error of the calculations.
- Crittenden, Christopher M.,Di Pasquale, Antonio G.
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p. 537 - 543
(2021/09/13)
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- Method for hydrogenolysis of halides
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The invention discloses a method for hydrogenolysis of halides. The invention discloses a preparation method of a compound represented by a formula I. The preparation method comprises the following step: in a polar aprotic solvent, zinc, H2O and a compound represented by a formula II are subjected to a reaction as shown in the specification, wherein X is halogen; Y is -CHRR or R; hydrogenin H2O exists in the form of natural abundance or non-natural abundance. According to the preparation method, halide hydrogenolysis can be simply, conveniently and efficiently achieved through a simple and mild reaction system, and good functional group compatibility and substrate universality are achieved.
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Paragraph 0232; 0254-0256
(2021/01/11)
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- Development of Selective Steroid Inhibitors for the Glucose-6-phosphate Dehydrogenase from Trypanosoma cruzi
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Chagas disease is a parasitic infection affecting millions of people across Latin America, imposing a dramatic socioeconomic burden. Despite the availability of drugs, nifurtimox and benznidazole, lack of efficacy and incidence of side-effects prompt the identification of novel, efficient, and affordable drug candidates. To address this issue, one strategy could be probing the susceptibility of Trypanosoma parasites toward NADP-dependent enzyme inhibitors. Recently, steroids of the androstane group have been described as highly potent but nonselective inhibitors of parasitic glucose-6-phosphate dehydrogenase (G6PDH). In order to promote selectivity, we have synthesized and evaluated 26 steroid derivatives of epiandrosterone in enzymatic assays, whereby 17 compounds were shown to display moderate to high selectivity for T. cruzi over the human G6PDH. In addition, three compounds were effective in killing intracellular T. cruzi forms infecting rat cardiomyocytes. Altogether, this study provides new SAR data around G6PDH and further supports this target for treating Chagas disease.
- Fredo Naciuk, Fabrício,Do Nascimento Faria, Jéssica,Gonc?lves Eufrásio, Amanda,Torres Cordeiro, Artur,Bruder, Marjorie
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supporting information
p. 1250 - 1256
(2020/07/27)
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- Dehalogenative Deuteration of Unactivated Alkyl Halides Using D2O as the Deuterium Source
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The general dehalogenation of alkyl halides with zinc using D2O or H2O as a deuterium or hydrogen donor has been developed. The method provides an efficient and economic protocol for deuterium-labeled derivatives with a wide substrate scope under mild reaction conditions. Mechanistic studies indicated that a radical process is involved for the formation of organozinc intermediates. The facile hydrolysis of the organozinc intermediates provides the driving force for this transformation.
- Xia, Aiyou,Xie, Xin,Hu, Xiaoping,Xu, Wei,Liu, Yuanhong
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p. 13841 - 13857
(2019/10/17)
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- 2-Iodoxybenzoic Acid Tosylates: the Alternative to Dess–Martin Periodinane Oxidizing Reagents
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Two powerful hypervalent iodine(V) oxidants, DMP-OTs (1-tosyloxy-1,1-diacetoxy-1H-1λ5-benzo[d][1,2]iodoxol-3-one) and IBX-OTs (1-tosyloxy-1-oxo-1H-1λ5-benzo[d][1,2]iodoxol-3-one) show high reactivity in the oxidation of structurally complex primary and secondary alcohols, which are highly functionalized polyketide or terpene fragments or steroids. The yields of the corresponding carbonyl compounds are even higher for the protocol that uses pyridine as additive. The oxidations proceed very rapidly at room temperature leaving the protective groups and π-systems intact and affording the corresponding carbonyl compounds in good to excellent yields. Moreover, IBX-OTs is an efficient reagent for the oxidative dehydrogenation of steroidal alcohols to the corresponding enones. (Figure presented.).
- Yusubov, Mekhman S.,Postnikov, Pavel S.,Yusubova, Roza Ya.,Yoshimura, Akira,Jürjens, Gerrit,Kirschning, Andreas,Zhdankin, Viktor V.
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p. 3207 - 3216
(2017/09/11)
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- Aqueous reduction of iodosteroids to deoxysteroids
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A new method for the reduction of iodosteroids to deoxysteroids has been developed using Zn, HCOOH and a catalytic amount of Aliquat 336 in water. In total, 13 iodosteroids were reduced in good to excellent yields. The higher solubilities of the substrates lead to the faster reactions, and the aqueous reaction was efficiently accelerated by granular polytetrafluoroethylene. The advantage of the aqueous system over eight organic solvents has also been demonstrated.
- Liu, Changsheng,Sun, Lili,Li, Chunbao
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p. 309 - 312
(2014/06/09)
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- Direct organocatalytic stereoselective transfer hydrogenation of conjugated olefins of steroids
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Kinetically controlled and organocatalytic syn-selective transfer hydrogenation has been successfully demonstrated for the reduction of the enone functional group of various steroids. Herein, diastereoselective synthesis of many 5β-steroids have been reported through organocatalysis, which have broad medicinal and pharmaceutical applications. The mechanistic studies and the selectivity of the products clearly indicated that the catalyst 1b·d-CSA is mild enough to activate the various chiral cyclic enones through iminium ion formation during the organocatalytic transfer hydrogenations with Hantzsch ester 2a as a hydrogen source. Further, clear evidence for the selective formation of intermediate iminium species [I]+ have been characterized through on-line monitoring of controlled experiments by NMR and ESI-HRMS analyses.
- Ramachary, Dhevalapally B.,Sakthidevi, Rajasekar,Reddy, P. Srinivasa
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p. 13497 - 13506
(2013/09/02)
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- PROGESTERONE RECEPTOR ANTAGONISTS AND USES THEREOF
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The present invention relates to a compound of formula (I): for its use as progesterone receptor antagonist, in particular for its use for the prevention and/or the treatment of cancer or uterine pathologies.
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Page/Page column 40
(2011/11/30)
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- Efficient chemoselective mild deprotection of S,S-and S,O-acetals and ketals with electrophilic halogens
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A novel and simple method for the chemoselective deprotection of S,S- and S,O-acetals and ketals in the presence of their O,O-analogs with electrophilic halogens to their corresponding carbonyl compounds is described using N-bromosuccinimide, N-chlorosuccinimide, 2,4,4,6-tetrabromo-2,5-cyclohexen-1- one, trichlorocyanuric acid, or molecular bromine in aqueous acetonitrile. The use of these reagents in the presence of hydrated silica gel provide efficient, novel, and mild procedures for the deprotection of cyclic and acyclic O,O-, S,S-, and S,O-acetals and ketals in excellent yields in short reaction times. Copyright Taylor & Francis Group, LLC.
- Shaterian, Hamid Reza,Hadadzadeh, Hassan
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p. 1059 - 1071
(2007/10/03)
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- Dehydroepiandrosterone (DHEA) congeners for prevention and/or treatment of ulcers
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The present invention is related to acute therapeutic uses of dehydroepiandrosterone (DHEA) congeners. These uses include methods for treating or preventing ulcers which comprise administering to a subject either at risk or in need thereof having an ulcer a therapeutic amount of DHEA congener.
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- A simple and efficient radical reduction using water-soluble radical initiator and hypophosphorous acid in aqueous alcohol
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A simple, mild and high-yielding procedure for the reduction of various halogenated compounds using a combination of the water-soluble radical initiater (VA-061), hypophosphorous acid and triethylamine in aqueous alcohol is reported. A simple, mild, and high-yielding procedure for the reduction of various halogenated compounds using a combination of the water-soluble radical initiator, 2,2′-azobis[2-(2-imidazolin-2-yl)propane] (VA-061), a water-soluble chain carrier, hypophosphorous acid, and the base, triethylamine, in aqueous alcohol is described. The reagents used in this method are all water soluble, and therefore, an almost pure desired product can be readily obtained using only an extraction procedure.
- Nambu, Hisanori,Alinejad, Anahita Hessamian,Hata, Kayoko,Fujioka, Hiromichi,Kita, Yasuyuki
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p. 8927 - 8929
(2007/10/03)
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- Method for reducing mast cell mediated allergic reactions
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The present invention is directed to a method for reducing mast cell mediated allergic reactions, including mast cell mediated allergy and asthma. Mast cell mediated allergic reactions, including type I hypersensitivity reasponse to allergens and asthma, are reduced by administering a dehydroepiandrosterone (DHEA) derivative to a patient in a manner which quickly raises blood levels of the active agent.
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- Method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue
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The present invention is related to a method for enhancing or accelerating re-epithelialization or re-endothelialization of a tissue. Examples of re-epithelialization in which the invention is particularly suited include, but are not limited to, re-epithelialization of (a) skin following surgical wounds, (b) skin abrasions caused by mechanical trauma, caustic agents or burns, (c) cornea following cataract surgery or corneal transplants, (d) mucosal epithelium (respiratory, gastrointestinal, genitourinary, mammary, oral cavity, ocular tissue, liver and kidney) following infection, nonpathological etiologies or drug therapy, (e) skin following grafting and (f) renal tubule following acute tubular necrosis. Examples of re-endothelialization in which the invention is particularly suited include, but are not limited to, re-endothelialization (or regrowth of endothelium) in blood vessels following angioplasty, and the lysis of fibrin clots or lysis or mechanical disruption of thrombi in coronary arteries. In accordance with the present invention, the time to complete re-epithelialization or re-endothelialization is enhanced or accelerated by administering a dehydroepiandrosterone (DHEA) derivative.
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- Methods for preventing progressive tissue necrosis, reperfusion injury, bacterial translocation and respiratory distress syndrome
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The present invention is related to a method for preventing or reducing the effects of ischemia. The ischemia may be associated with injury or reperfusion injury, such as occurs as a result of infarctions, thermal injury (bums), surgical trauma, accidental trauma, hemorrhagic shock and the like. The invention is also related to methods for preventing, or reducing bacterial translocation, adult respiratory distress syndrome, adherence of blood cells and platelets to endothelial cells and pulmonary hypertension. In accordance with the present invention, these conditions are prevented or reduced by administering a dehydroepiandrosterone (DHEA) derivative as defined herein.
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- Mechanistic studies of deoxygenation of steroidal ring-D 16,17-ketols with trimethylsilyl iodide
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Deoxygenation reaction of steroidal 16,17-ketols 1, 2 and 6 as well as their silyl ethers 3 and 7 and 16- and 17-iodoketone analogs 11, 12, and 14 with trimethylsilyl iodide (TMSI) or HI under various conditions was examined. The results indicate that the deoxygenation producing 16- and 17- ketones 9 and 8 proceeds through multiple reaction pathways; a direct iodination of a siloxy group of the ketol silyl ethers by iodide ion to give the iodoketones (path b), addition of TMSI to a carbonyl group of the ketol silyl ethers to yield diiodo derivatives 22 and 23 through iodo-bis-TMS compounds 20 and 21 (path a), and cleavage of ether bond of dimers 15-18 initially produced are, at least, involved. In these sequences, rearrangement of the 16-ketols 1 and 2 to the 17 β-ketol 6 also plays a significant role. The yields of the ketones 9 and 8 and their relative amounts would be dependent on the relative importance of each pathway in the reaction.
- Nagaoka, Masao,Nagasawa, Etsuko,Sato, Sadao,Numazawa, Mitsuteru
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p. 548 - 553
(2007/10/03)
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- Deoxygenation of steroidal ring-D 16,17-ketols with trimethylsilyl iodide
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Reaction of various steroidal 16,17-ketols, 16α-hydroxy-17-ketones 1- 3, and 15, 16β-hydroxy-17-ketone 4, and 17β-hydroxy-16-ketones 5-7, and 17, along with methyl ethers of 16α- and 17β-ketols 1 and 5, with an excess of trimethylsilyl iodide (TMSI) or with HI in CHCl3, produced the deoxygenated products, a mixture of the corresponding 17- and 16-ketones, in low to quantitative yields, in which the 17-ketone was the major product in each ease. When the 16β-deuterated 16α-ketol 3 and the 17α-deuterated 17β- ketol 7 were reacted with TMSI for a brief period (15 min), the deuterium content at C-16β and C-17α of the recovered steroids 3 and 7 was reduced by 17 and 35%, respectively. The present results indicate that the deoxygenation proceeds not only through a direct iodination pathway producing α-iodoketone but also through other reaction pathways.
- Nagaoka, Masao,Nagasawa, Etsuko,Numazawa, Mitsuteru
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p. 1857 - 1861
(2007/10/03)
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- Deoxygenation of aliphatic alcohols via reduction of new thioxocarbamate derivatives
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N-Acylthioxocarbamates, obtained by the reaction of alcohols with acyl isothiocyanates, were reduced by tributylstannane or triphenylsilane under radical conditions to give deoxygenated products of the corresponding alcohols in good yields. An application to regioselective deuteration using tributyldeuteriostannane is also examined.
- Oba,Nishiyama
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p. 624 - 628
(2007/10/02)
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- Ultrasound assisted zinc reactions in synthesis 2. A new Clemmensen-type reduction
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A mild and efficient method is described for the reduction of carbonyls to methylene groups. Under ultrasonic irradiation, deoxygenation of 3-oxosteroids with zinc dust in acetic acid or acetic acid/water was achieved in 15 minutes. The observed selectivity at C-3 in the presence of 17- and 20-oxo groups is discussed.
- Salvador,Sa E Melo,Campos Neves
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p. 361 - 362
(2007/10/02)
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- Desulfurization with Nickel and Cobalt Boride: Scope, Selectivity, Stereochemistry, and Deuterium-Labeling Studies
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A variety of organosulfur compounds containing alkylthio and arylthio groups underwent reductive desulfurization under notably mild conditions when treated with nickel boride, generated in situ from nickel chloride hexahydrate and sodium borohydride in methanol-THF (3:1).Phenyl, chloro, and ester groups are not reduced under these conditions, while iodo, bromo, nitrile, aldehyde, ketone, cyclopropane, and olefinic functions are reduced either completely or partially.Deuterium-labeling studies indicate that the hydrogen that is incorporated into the product originates from both the sodium borohydride and the protic solvent, suggesting the intermediacy of dihydrogen.The epimers 3α- and 3β-(phenylthio)cholestane afforded 3α- and 3β-deuteriocholestane, respectively, demonstrating that the reaction proceeds with retention of configuration.The method may thus be employed for the stereospecific preparation of deuterated products from organosulfur compounds.Arguments are presented in support of a tentative mechanism involving an oxidative addition-reductive elimination sequence via a nickel hydride intermediate.
- Back, Thomas G.,Baron, Denise L.,Yang, Kexin
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p. 2407 - 2413
(2007/10/02)
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- Chromium(VI) Based Oxidants; IV. Zinc Chlorochromate Nonahydrate as an Efficient and Mild Oxidizing Agent
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Zinc chlorochromate nonahydrate is an easily prepared and a cheap oxidizing agent for the oxidation of different types of hydroxy compounds, unsaturated hydrocarbons, and benzylic carbon hydrogen bonds at room temperature in dichloromethane.
- Firouzabadi, H.,Sharifi, A.
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p. 999 - 1002
(2007/10/02)
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- Method for prophylaxis of obesity
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STR1 useful as anti-cancer, anti-obesity, anti-hyperglycemic, anti-autoimmune and anti-hypercholesterolemic agent.
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- Barium Permanganate, Ba(MnO4)2, a versatile and mild oxidizing agent for use under aprotic and non-aqueous conditions
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Barium Permanganate is an easily prepared, stable, and a versatile oxidation reagent. With this reagent different types of primary and secondary hydroxy compounds are converted to their carbonyl derivatives. Aldehydes could be transformed to their carboxylic acids. Benzylic chloride and bromides are converted to their aldehydes and carboxylic acids. Semicarbazide and 2,4-dinitrophenylhydrazine derivatives of benzylic carbonyl compounds undergo carbon-nitrogen bond cleavage selectively and yield the expected carbonyl compounds. p-Hydroquinone is converted to p-benzoguinone and aromatic amines to their azo compounds. Anthracene and phenanthrene produce their 9,10-quinones. Diphenyl acetylene and trans stilbene give benzil, and styrene produces benzaldehyde. Selective oxidations of secondary benzylic carbon-hydrogen bonds occur and the corres- ponding carbonyl compounds are produced in good yields.
- Firouzabadi,Seddighi,Mottaghineiad,Bolourchian
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p. 6869 - 6878
(2007/10/02)
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- 17-Hydroxy-steroids
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Compounds of the formulae: STR1 are useful as anti-cancer, anti-obesity, anti-diabetic, anti-coronary agents, anti-aging agents, anti-hypolipidemic agents and anti-autoimmune agents.
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- Microbial Oxidation of Sterol Side-Chains
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Several sterol metabolising microorganisms, Pseudomonas convexa, P. stutzeri, Micrococcus sp., Cephalosporium longisporum and Moraxella sp. were isolated from soil on 2-cyclopentyl-6-methyl heptane and cholestane as carbon sources.All these organisms were shown to have the capacity of oxidizing the eight carbon side chain of cholesterol.Excepting P. convexa, the organisms needed a chelating agent for prevention of steroid ring degradation.The Moraxella sp. proved to be the most versatile as it degraded cholesterol derivatives such as 3β-methoxy cholest-5-ene, 3β-chloro cholest-5-ene, 3,5-cyclocholestan-6-one and potassium cholesteryl sulphate to the corresponding 17-keto steroids in 10-50percent yield in shake flasks.It also gave high yields of estrone from both 19-hydroxy-3β-acetoxy cholest-5-ene and 19-hydroxy-3β-acetoxy sitost-5-ene.Two new enzymes one carrying out the oxidative O-demethylation of 6β-methoxy 3,5-cyclocholestane and the other, the isomerisation of i-steroids to normal 3β-hydroxy-Δ5 steroids were discovered.Immobilized Moraxella cells in agar carried out the side chain degradation of cholesteryl sulphate to yield 3β-hydroxy androst-5-en-17-one sulphate and the 19-hydroxy-3β-acetoxy derivatives of both cholesterol and sitosterol to estrone in high yields.The half life of entrapped cells was estimated to be 28 days.
- Bhattacharyya, P. K.,Rao, M. Krishna,Natarajan, Rama Devi,Ramgopal, Malathi,Madyastha, Prema,Madyastha, K. M.
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- SYNTHETICALLY USEFUL OXIDATIONS AT SOLID PERMANGANATE SURFACES
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Solid NaMnO4.H2O is an efficient and selective oxidizing agent.
- Menger, Fredric M.,Lee, Chuan
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p. 1655 - 1656
(2007/10/02)
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- Formation of vinyl halides from vinyl cations generated by acetylenic participation in biomimetic polyene cyclizations
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The object of this study was to examine the fate of vinyl cations of type 4 (resulting from biomimetic polyene cyclizations) in the presence of various halides as sources of nucleophiles. Treatment of the dienynol 1 with trifluoroacetic acid in methylene chloride for 45 min at -78°C resulted in the isolation of the rearranged bicyclic vinyl chloride 6 in 56% yield. Confirmation of the structure and isomeric purity of 6 was obtained by exhaustive ozonization to give diketo ester 9 followed by Wolff-Kischner reduction and then esterification to yield ester 10, the structure of which was confirmed by hydrogen-deuterium exchange of the protons α to the carbomethoxy group. The configuration of the ring fusion in 6 was shown to be trans in the following manner. Selective ozonization gave chloro ketone 11, which was converted into chloro olefin 12 by Wolff-Kischner reduction. Further ozonization afforded keto ester 13, which was converted into diacid 15 by sodium hypobromite oxidation. Esterification afforded diester 16, which was identical with the material obtained via Wolff-Kischner reduction of the known keto diester 17. More careful examination of the products from the aforementioned cyclization also showed the presence of 8% ketone 8 (after hydrolytic workup). Identical cyclization conditions of 1, except at 0°C, gave 55% vinyl chloride 6 and 45% ketone 8 while use of a 7.5:1 pentane-1,2-dichloroethane mixture at 0°C led to 11% vinyl chloride 6 and 89% ketone 8. Cyclization of dienynol 1 with stannic chloride in 1,1-dichloroethylene at -35°C for 45 min gave a 53% yield of three isomeric vinyl chlorides, 7b, 7a, and 6, in a ratio of 8:75:12. The successful cyclization of dienynol 1 led to more extensive cyclization studies of substrates such as 2, 3, and 35, which provided tetracyclic products. The most thoroughly studied case was that of trienynol 3, which, on treatment with stannic chloride in 1,1-dichloroethylene at ca. -30°C for 50 min, gave a 64% yield of three tetracyclic products A, B, and C in a ratio of 15:73:12 by VPC. Product A was shown to be chloro diene 22 by hydrogenation of the Δ1-olefinic bond followed by ozonization to give 5β,13α-androstan-17-one (29), which was compared with an authentic sample prepared by irradiation of 5β-androstan-17-one (25). Products B and C were shown to be chloro dienes 18 and 20 by conversion of the mixture into 5β-androstan-17-one (25) and keto ester 27. A systematic variation of reaction conditions as well as the use of mixed-halide sources led to evidence for a possible mechanism for the formation of all three products from an intermediary tricyclic cation 43.
- Johnson, William S.,Ward, Carl E.,Boots, Sharon G.,Gravestock, Michael B.,Markezich, Ronald L.,McCarry, Brian E.,Okorie, Dominic A.,Parry, Ronald J.
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- The Solvolysis of 4β-Hydroxy-3β-p-tolylsulphonyloxyandrost-5-enes
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The solvolysis of 3β-p-tolylsulphonyloxyandrost-5-enes in acetic acid containing sodium acetate, is retarded by the presence of a 4β-acetoxy- or hydroxy-group.The products of solvolysis include the A-nor-3-formyl-steroids except in the presence of a 7-ketone.
- Hanson, James R.,Wadsworth, Harry J.
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p. 933 - 937
(2007/10/02)
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- 14 β-Hydroxy 3-deoxycardenolides
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Novel compounds of the formula STR1 useful as pharmaceutical compounds are disclosed. Processes are also disclosed for their preparation.
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