- Catalytic cyclometallation in steroid chemistry V: Synthesis of hybrid molecules based on steroid oximes and (5Z,9Z)-tetradeca-5,9-dienedioic acid as potential anticancer agents
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Synthetic analogues of natural 5Z,9Z-dienoic acids - hybrid molecules based on the oximes of cholesterol, pregnenolone, and androsterone with 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid - were synthesized for the first time and studied for antitumor activity in vitro. The acid was prepared using catalytic cyclomagnesiation of O-containing 1,2-dienes with Grignard reagent in the presence of Cp2TiCl2 as the key step. Using flow cytometry, it was shown for the first time that the new molecules are efficient apoptosis inducers in the HeLa, Hek293, U937, Jurkat, and K562.
- D'yakonov, Vladimir A.,Tuktarova, Regina A.,Dzhemileva, Lilya U.,Ishmukhametova, Svetlana R.,Yunusbaeva, Milyausha M.,Dzhemilev, Usein M.
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Read Online
- Synthesis of new 7-aminosterol squalamine analogues with high antimicrobial activities through a stereoselective titanium reductive amination reaction
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A series of 7-amino- and polyaminosterol analogues of squalamine and trodusquemine were synthesized involving a new stereoselective titanium reductive amination reaction in high chemical yields of up to 95% in numerous cases. These derivatives were evaluated for their in vitro antimicrobial properties against human pathogens. All the compounds present excellent activities against Gram-positive bacteria exhibiting similar results against Staphylococcus aureus and Streptococcus faecalis with minimum inhibitory concentrations (MICs) varying from 2.5 to 10 μg/mL. Numerous derivatives possess also MICs against Gram-negative Escherichia coli bacteria (MICs varying from 2.5 to 10 μg/mL) suggesting that nature of the amino group attached to the sterol moiety plays an important role on the activities of such products.
- Loncle, Celine,Salmi, Chanaz,Letourneux, Yves,Brunel, Jean Michel
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Read Online
- Partial separation of enantiomeric 1,2-diols via ketal formation with a polymer-supported chiral ketone
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Partial separations of the (R,R)- and (S,S)-enantiomers of butane-2,3-diol, trans-cyclohexane-1,2-diol and dimethyl tartrate were achieved via ketal formation with a polymer-supported 7-keto steroid; in each case one enantiomer reacted in higher yield than the other and release of the diols from the support gave diol fractions significantly enriched in one enantiomer.
- Clarke, Ian D.,Hodge, Philip
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Read Online
- Synthesis of 7α- and 7β-spermidinylcholesterol, squalamine analogues
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Stereoselective synthesis of squalamine dessulfates analogues, 7α and 7β-N-[3N-(4-aminobutyl) aminopropyl]aminocholesterol are reported, using 7α and 7β-aminocholesterol as a key intermediate. It's the first example in which the position of spermidine is modified at the steroid ring. These molecules showed a comparable antibacteria and fungi activities to squalamine. Then, they have a cytotoxic activity on a human non-small cell bronchopulmonary carcinoma line (NSCLC-N6).
- Choucair,Dherbomez,Roussakis,El Kihel
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Read Online
- Cooperative Noncovalent Interactions Lead to a Highly Diastereoselective Sulfonyl-Directed Fluorination of Steroidal α,β-Unsaturated Hydrazones
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A series of steroidal α,β-unsaturated hydrazones is presented whose behavior and reactivity are governed by various types of weak C-H hydrogen bonds. Several interesting features in a representative X-ray crystal structure and 1H NMR spectrum are examined that provide evidence for a unique bifurcated intramolecular C-H interaction. Moreover, these steroid derivatives undergo functionalization in the form of a highly regio- and stereoselective fluorination; the sulfonyl oxygen atoms are proposed to direct the fluorinating reagent through C-H hydrogen bonds.
- Capilato, Joseph N.,Siegler, Maxime A.,Rowshanpour, Rozhin,Dudding, Travis,Lectka, Thomas
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p. 1300 - 1307
(2021/01/09)
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- Preparation method of 7-keto-cholesterol acetate
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The invention relates to a preparation method of 7-keto-cholesteryl acetate. Specifically, according to the method provided by the invention, cholesteryl acetate is taken as a raw material, Salen Cu (II) is taken as a catalyst, air or pure oxygen is taken as an oxidant, and the 7-keto-cholesteryl acetate is prepared with high yield, high purity, simple process and low cost.
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Paragraph 0068-0074
(2021/06/26)
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- Novel industrial method for preparing vitamin D3 by taking stigmasterol as raw material
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The invention provides a novel industrial method for preparing vitamin D3 by taking stigmasterol as a raw material. The method comprises the following steps: sequentially carrying out hydroxyl acetylation, side chain oxidation, side chain isopentane reduction and hydrogenation on stigmasterol to obtain cholesterol acetate, and then sequentially carrying out oxidation, hydrazone formation, hydrazone removal, hydrolysis, illumination and the like to obtain the vitamin D3. The invention provides a novel method for preparing vitamin D3 from stigmasterol, and the method has the advantages of mild reaction conditions and high yield, and is suitable for industrial production.
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Paragraph 0010; 0046; 0047
(2021/05/05)
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- Synthesis and search for 3β,3′β-disteryl ethers after high-temperature treatment of sterol-rich samples
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It has been proven that at increased temperature, sterols can undergo various chemical reactions e.g., oxidation, dehydrogenation, dehydration and polymerisation. The objectives of this study are to prove the existence of dimers and to quantitatively analyse the dimers (3β,3′β-disteryl ethers). Sterol-rich samples were heated at 180 °C, 200 °C and 220 °C for 1 to 5 h. Quantitative analyses of the 3β,3′β-disteryl ethers were conducted using liquid extraction, solid-phase extraction and gas chromatography coupled with mass spectrometry. Additionally, for the analyses, suitable standards were synthetized from native sterols. To identify the mechanism of 3β,3′β-disteryl ether formation at high temperatures, an attempt was made to use the proposed synthesis method. Additionally, due to the association of sterols and sterol derivatives with atherosclerosis, preliminary studies with synthetized 3β,3′β-disteryl ethers on endothelial cells were conducted.
- Bus, Katarzyna,Ofiara, Karol,Sitkowski, Jerzy,Szterk, Arkadiusz,Zmys?owski, Adam
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- Preparation method and application of 7-ketocholesterol acetate
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The invention relates to a preparation method of 7-ketocholesterol acetate. The preparation method comprises the following steps: (1) dissolving cholesterol acetate, a catalyst, an initiator and an antioxidant in a mixed solvent to obtain a first mixed solution, and introducing oxygen into the first mixed solution to perform oxidation reaction on cholesterol acetate and oxygen to obtain a second mixed solution; and (2) treating the second mixed solution to obtain the 7-ketocholesterol acetate. The invention also relates to an application of the 7-ketocholesterol acetate obtained by the preparation method in preparation of 7-dehydrocholesterol. According to the preparation method, the antioxidant is added so that free radicals of reactants in a reaction system can be effectively prevented from being subjected to polymerization reaction, the reaction selectivity can be improved, and the yield and the purity of the target product 7-ketocholesterol acetate can be improved.
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Paragraph 0043-0070
(2020/11/26)
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- 7-keto-cholesterol acetate preparation method
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The invention discloses a 7-keto-cholesterol acetate preparation method, wherein the preparation method comprises the following steps: (1) carrying out an oxidation reaction on cholesterol acetate andair in a reaction solvent under the catalysis of an N-hydroxyl derivative and a transition metal salt, and controlling the conversion rate of the oxidation reaction to be 60-80% to obtain an oxidation reaction liquid; and (2) concentrating the oxidation reaction solution to remove the reaction solvent, then adding an extraction solvent, separating out the N-hydroxyl derivative, then adding aceticanhydride and an organic alkali to carry out a dehydration reaction, and after the reaction is completed, carrying out post-treatment to obtain the 7-keto-cholesterol acetate product and a cholesterol acetate raw material. By adopting the preparation method disclosed by the invention, byproducts of the oxidation reaction can be reduced, and the total yield of the reaction and the purity of the 7-keto-cholesterol acetate product are improved.
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Paragraph 0035-0066
(2020/03/29)
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- Preparation method for intermediate, namely 7-ketocholesterol acetate of vitamin D3
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The invention discloses a preparation method for an intermediate, namely 7-ketocholesterol acetate of vitamin D3. The preparation method comprises the following steps: under the actions of a main catalyst, a cocatalyst and an initiator, carrying out an oxidation reaction on cholesterol acetate by using oxygen as an oxidant, and carrying out after-treatment after the reaction is finished so as to obtain the 7-ketocholesterol acetate, wherein the main catalyst is N-hydroxyphthalimide; the cocatalyst is water-absorbent resin; and the initiator is at least one selected from the group consisting ofmanganese acetate and cobalt acetate. According to the invention, by adoption of the water-absorbent resin (SAP) as the cocatalyst, generation of the oxidation reaction can be effectively promoted, so the yield of a product is improved, and the mode of after-treatment is simplified; meanwhile, the main catalyst and the cocatalyst are cheap and easily available, and can be recycled for six times or more; high reaction selectivity and high conversion rate are achieved; and the preparation method is highly-efficient and has low cost.
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Paragraph 0029-0042
(2020/06/02)
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- Carbonyl-Directed Aliphatic Fluorination: A Special Type of Hydrogen Atom Transfer Beats out Norrish II
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Recently, our group reported that enone and ketone functional groups, upon photoexcitation, can direct site-selective sp3 C-H fluorination in terpenoid derivatives. How this transformation actually occurred remained mysterious, as a significant number of mechanistic possibilities came to mind. Herein, we report a comprehensive study describing the reaction mechanism through kinetic studies, isotope-labeling experiments, 19F NMR, electrochemical studies, synthetic probes, and computational experiments. To our surprise, the mechanism suggests intermolecular hydrogen atom transfer (HAT) chemistry is at play, rather than classical Norrish hydrogen atom abstraction as initially conceived. What is more, we discovered a unique role for photopromoters such as benzil and related compounds that necessitates their chemical transformation through fluorination in order to be effective. Our findings provide documentation of an unusual form of directed HAT and are of crucial importance for defining the necessary parameters for the development of future methods.
- Ghorbani, Fereshte,Harry, Stefan Andrew,Capilato, Joseph N.,Pitts, Cody Ross,Joram, Jacob,Peters, Garvin N.,Tovar, John D.,Smajlagic, Ivor,Siegler, Maxime A.,Dudding, Travis,Lectka, Thomas
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supporting information
p. 14710 - 14724
(2020/10/13)
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- New industrial method for producing vitamin D3 by taking wool fat as raw material
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The invention provides a new industrial method for producing vitamin D3 by taking wool fat as a raw material. The new industrial method comprises the following steps: carrying out saponification and primary purification on the wool fat in a low alcohol solution, thus obtaining a cholesterol crude product; directly carrying out acetylation on the cholesterol crude product, thus obtaining high-purity cholesterol acetate; then sequentially carrying out oxidizing, hydrazone forming, hydrazone removing, hydrolyzing, illuminating and the like, thus obtaining the vitamin D3. A production technology disclosed by the invention is efficient, green and environment-friendly, is high in product yield and is suitable for industrial production, and the manufacturing cost of the vitamin D3 is greatly reduced; a saponification technology is ingenious in filtrate treatment, has no generation of waste liquid and waste and is more beneficial for environment protection.
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- Chemical synthesis of 7α-hydroxycholest-4-en-3-one, a biomarker for irritable bowel syndrome and bile acid malabsorption
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7α-Hydroxy-cholest-4-en-3-one is a biomarker for bile acid loss, irritable bowel syndrome, and other diseases associated with defective bile acid biosynthesis. Furthermore, 7α-hydroxy-cholest-4-en-3-one is the physiological substrate for cytochrome P450 8B1 (P450 8B1 or CYP8B1), the oxysterol 12α-hydroxylase enzyme implicated in obesity and cardiovascular health. We report the chemical synthesis of this physiologically important oxysterol beginning with cholesterol. The key feature of this synthesis involves a regioselective C3-allylic oxidation of a 3-desoxy-Δ4-7α-formate steroid precursor to form 7α-formyloxy-cholest-4-en-3-one, which was saponified to yield 7α-hydroxy-cholest-4-en-3-one.
- Offei, Samuel D.,Arman, Hadi D.,Yoshimoto, Francis K.
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- Compounds that are Analogs of Squalamine, Used as Antibacterial Agents
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The invention relates to compounds of formula (I), to the pharmaceutical compositions comprising same, and to the use thereof in the treatment of bacterial, fungal, viral and parasitic infections or in the treatment of cancer in humans or animals. In formula (I), R1 and R2 are as defined in claim 1.
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- Metal-Free Allylic Oxidation of Steroids Using TBAI/TBHP Organocatalytic Protocol
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A mild, efficient and organocatalytic allylic oxidation of steroids using a TBAI/TBHP protocol has been developed. A range of bioactive Δ5-en-7-ones can be easily prepared from the corresponding Δ5-steroids. The methodology features several advantages, including readily available starting materials, environmentally benign oxidant, high functional group compatibility, and metal-free catalysis.
- Lam, Ying-Pong,Yeung, Ying-Yeung
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supporting information
p. 2369 - 2372
(2018/04/19)
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- 7-oxo cholesteryl acetate preparation method
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The invention relates to the field of organic synthesis, particularly to a 7-oxo cholesteryl acetate preparation method, which comprises: in a first solvent, in the presence of a catalyst and an initiator, under the action of ultrasonic waves, carrying out an oxidation reaction on cholesteryl acetate and oxygen-containing gas to obtain the oxidation product of the cholesteryl acetate, wherein thecatalyst is one or a plurality of materials selected from N-hydroxyimide compounds, and the initiator is one or a plurality of materials selected from azo compounds and organic peroxides; and in a second solvent, in the presence of alkylamine and anhydride, carrying out a dehydration reaction on the oxidation product of the cholesteryl acetate to obtain the 7-oxo cholesteryl acetate. According tothe present invention, with the method, the high-yield and high-purity 7-oxo cholesteryl acetate can be obtained by using the low-pollution and low-cost catalyst system under the set specific oxidation reaction conditions under the action of ultrasonic waves.
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Paragraph 0030; 0055; 0067; 0068; 0070; 0071
(2018/06/15)
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- NANOEMULSIONS AND METHODS FOR CANCER THERAPY
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An oxysterol or oxysterol-like compound is provided, which finds use in treating and/or targeting cancer.
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- 7-keto cholesteryl-9-carboxyl nonane and synthesis method of fluorescent marker thereof
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The invention relates to 7-keto cholesteryl-9-carboxyl nonane and a synthesis method of a fluorescent marker thereof. Cholesterol and azelaic acid are used as raw materials, 1,3-dicyclohexyl carbodiimide and 4-dimethylamino pyridine are used as a catalyst for synthesis reaction, and dichloromethane is used as a solvent to establish an oxidation system, and finally the 7-keto cholesteryl-9-carboxyl nonane is obtained through fat reduction reaction. The synthesis method of the 7-keto cholesteryl-9-carboxyl nonane is simple and convenient to operate, the raw materials are easy to obtain, the impurity content is low, and the production cost is low. The invention further provides a synthesis method of NBD-fluorescent group introduced 7-keto cholesteryl-9-carboxyl nonane. NBD-fluorescent groups are introduced on the basis that a basic framework structure is ensured, and finally NBD-oxLig-1 is synthesized so that the 7-keto cholesteryl-9-carboxyl nonane (oxLig-1) can produce spontaneous fluorescence and is used for tracer application in cell biology.
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- Steroid zinc metal complex and method of preparing the same and in the preparation of anti-stomach cancer application of the medicament (by machine translation)
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A steroid zinc metal complex and method of preparing the same and in the preparation of anti-stomach cancer application of the medicament. Complex is the chemical name: dichloroborane · [3 β-acetoxy, cholest-5-ene-7- shrinks the ammonia thiourea-N, S] zinc (II) are, the structural formula is as follows: The preparation method comprises the following steps: 1) 3 β-acetoxy, cholest-5-ene preparation; 2) 3 β-acetoxy, cholest-5-ene-7-one preparation; 3) 3 β-acetoxy, cholest-5-ene-7- shrinks the ammonia thiourea preparation; 4) dichloroborane · [3 β-acetoxy, cholest-5-ene-7- shrinks the ammonia thiourea-N, S] preparation of a zinc (II). The in vitro anti-tumor experiments show that, · dichloroborane of the present invention [3 β-acetoxy, cholest-5-ene-7- shrinks the ammonia thiourea-N, S] zinc (II) are compounds with strong anti-gastric cancer activity. (by machine translation)
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- Synthesis method of vitamin D3 intermediate 7-ketocholesteryl acetate
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The invention discloses a synthesis method of a vitamin D3 intermediate 7-ketocholesteryl acetate, and relates to 7-ketocholesteryl acetate. The method comprises the following steps: adding cholesteryl acetate to a mixed solvent, introducing oxygen as an oxidant, adding a main catalyst and a nonmetal cocatalyst, carrying out a catalytic allylic oxidation reaction, and purifying the obtained reaction product to obtain the vitamin D3 intermediate 7-ketocholesteryl acetate. No complex post-treatment processes are needed; a quaternary ammonium salt is adopted as the cocatalyst, so decomposition of peroxides is effectively promoted; tetrahydrofuran azeotropic water removal is adopted to remove water generated in the decomposition process of the peroxides, so the decomposition is complete, and the reaction is fast and mild; and he main catalyst and the cocatalyst are nonmetal catalysts respectively, and are cheap and easily available, the main catalyst can be reused 5 or more times, the conversion rate and the selectivity are respectively high, and the reaction yield reaches 85% or above, so the synthesis method has the advantages of high efficiency and low cost.
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Paragraph 0020; 0021
(2017/01/02)
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- Site-selective and metal-free aliphatic C-H oxidation enabled synthesis of [5,24,25-d3]-(25s)-δ7-dafachronic acid
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Steroid hormones play significant roles in both worms and mammalians. (25S)-Δ7-Dafachronic acid (Δ7-DA, 1) is a member of the dafachronic acid hormonal series that regulates both development and lifespan of C. elegans. Despite its importance, effective tools for the illumination of its mode of action are lacking. Herein, we report an efficient synthesis of trideuterated Δ7-DA, [5,24,25-D3]-(25S)-Δ7-dafachronic acid ([D3]-Δ7-DA, 2), as a useful chemical tool for subsequent biological studies. Key steps for this bioinspired synthesis approach include site-selective aliphatic C-H oxidation mediated by methyl(trifluoromethyl)dioxirane (TFDO), and the iridium/phosphine-oxazoline-catalyzed late-stage asymmetric deuterium reduction. Bio is best! [5,24,25-D3]-(25S)-Δ7-Dafachronic acid, an isotope-labeled steroid hormone has been synthesized in 14 steps from cholesterol inspired by biosynthesis. Key steps include a site-selective and metal-free aliphatic C-H oxidation and a late-stage catalytic asymmetric deuteration (see scheme). [5,24,25-D3]-(25S)-Δ7-Dafachronic acid will be severed as an effective chemical tool for the illumination of novel molecular mechanisms of longevity.
- Liu, Weilong,Li, Xiangke,Chen, Jie,Li, Tiemei,Dong, Mengqiu,Lei, Xiaoguang
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p. 5345 - 5349
(2015/03/30)
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- Allylic oxidation of steroidal olefins by vanadyl acetylacetonate and tert-butyl hydroperoxide
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Abstract Readily available vanadyl acetylacetonate was found to oxidize the allylic sites of Δ5 steroidal alcohols without protection of hydroxyl groups. Cholesterol, dehydroepiandrosterone, cholesterol benzoate, cholesterol acetate, pregnenolone, and 5-pregnen-3,20-diene were oxidized to 7-keto products using vanadyl acetylacetonate in one pot reactions at room temperature in the presence of oxygen and water.
- Grainger, Wendell S.,Parish, Edward J.
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p. 103 - 109
(2015/06/30)
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- Oxyphytosterols as active ingredients in wheat bran suppress human colon cancer cell growth: Identification, chemical synthesis, and biological evaluation
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Consumption of whole grains has been reported to be associated with a lower risk of colorectal cancer. Recent studies illustrated that phytochemicals in wheat bran (WB) may protect against colorectal cancer. There is a growing interest in the phytosterol contents of foods as either intrinsic or added components due to their beneficial health effects. However, little is known whether phytosterols in WB contribute the observed chemopreventative activity of the grain. In the present study, we directly purified and identified four oxyphytosterols 1-4 from sterol-enriched fraction of WB, and also successfully synthesized five sterol oxides 5-8 and 13. Using these nine compounds as references, we outlined a comprehensive profile of steroids in WB using tandem liquid chromatography mass spectrometry with electrospray ionization (LC-ESI/MSn, n = 2-3) techniques for the first time. Among them, three sterol oxides 13, 14, and 18 are novel compounds, and 14 compounds 3, 4, 6-11, 13, 14, 16, and 18-20 were reported in WB for the first time. Our results on the inhibitory effects of available sterol oxides 1-8 and 13 against the growth of human colon cancer cells HCT-116 and HT-29 showed that compounds 2-8 exerted significant antiproliferative effects, with oxysterol 8 being the most active one in both cells. We further demonstrated that four most active sterol oxides 5-8 could induce cell death through the apoptosis pathway. Our results showed that phytosterols, particularly oxyphytosterols, in WB possess significant antiproliferative properties, and thereby may greatly contribute the observed chemoprevention of the whole grain wheat.
- Zhu, Yingdong,Soroka, Dominique,Sang, Shengmin
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p. 2267 - 2276
(2015/03/14)
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- MnO2/TBHP: A Versatile and User-Friendly Combination of Reagents for the Oxidation of Allylic and Benzylic Methylene Functional Groups
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In the presence of activated MnO2, tert-butyl hydroperoxide (TBHP) in CH2Cl2 is able to oxidize the allylic and benzylic methylene groups of different classes of compounds. I describe a one-pot oxidation protocol based on two sequential steps. In the first step, carried out at low temperature, MnO2 catalyses the oxidation of the methylene group. This is followed by a second step where reaction temperature is increased, allowing MnO2 both to catalyse the decomposition of unreacted TBHP and to oxidize allylic alcohols that could possibly be formed. The proposed oxidation procedure is generally applicable, although its efficiency, regioselectivity, and chemoselectivity are strongly dependent on the structure of the substrate. A simple and user-friendly synthetic procedure for the oxidation of allylic and benzylic methylene groups to the corresponding conjugated carbonyl derivatives is described. The proposed oxidation protocol is based on the combined use of MnO2 and tert-butyl hydroperoxide, and is generally applicable.
- Serra, Stefano
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p. 6472 - 6478
(2015/10/19)
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- Selective reduction of α,β-unsaturated steroidal carbonyl compounds by NaBH4in presence of guanidine hydrochloride in dioxane
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A selective hydrogenation of α,β-unsaturated steroidal carbonyl compounds with NaBH4in the presence of guanidine hydrochloride in dioxane in good to excellent yields are described.
- Khan, Salman Ahmad,Asiri, Abdullah M.
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p. 6331 - 6334
(2015/02/19)
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- Synthesis of steroidal and nonsteroidal vicinal heterocyclic alcohols, N-(1-cycloalkenyl)heterocycles and their antibacterial studies
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A solvent free steroidal and nonsteroidal epoxide ring opening reaction by nitrogen containing heterocycles under microwave irradiation is described. Some of the epoxide ring opening compounds were converted to their corresponding N-(1-cycloalkenyl)heterocycles via an acid catalyzed dehydration reaction. The antimicrobial activities of the epoxide ring opening compounds and N-(1-cycloalkenyl)heterocyclic compounds were tested by agar diffusion assay. Compounds 6, 9-12, 24 and 27 showed moderate inhibition against the growth of pathogenic bacteria Escherichia coli, Pseudomonas syringae, Bacillus subtilis, Proteus vulgaris and Staphylococcus aureus.
- Saikia, Pallabi,Kaishap, Partha Pratim,Goswami, Jonalee,Singh, Anil Kumar,Deka Boruah, Hari Prasanna,Gogoi, Sanjib,Boruah, Romesh C.
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- Structure-activity relationships of oxysterol-derived pharmacological chaperones for Niemann-Pick type C1 protein
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Niemann-Pick disease type C is a fatal neurodegenerative disease, and its major cause is mutations in NPC1 gene. This gene encodes NPC1 protein, a late endosomal polytopic membrane protein required for intracellular cholesterol trafficking. One prevalent mutation (I1061T) has been shown to cause a folding defect, which results in failure of endosomal localization of the protein, leading to loss-of-function phenotype. We have previously demonstrated that several oxysterols and their derivatives act as pharmacological chaperones; binding of these compounds to NPC1I1061T mutant protein corrects the localization/maturation defect of the mutant protein. Here, we disclose detailed structure-activity relationships of oxysterol derivatives as pharmacological chaperones for NPC1I1061T mutant.
- Ohgane, Kenji,Karaki, Fumika,Noguchi-Yachide, Tomomi,Dodo, Kosuke,Hashimoto, Yuichi
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supporting information
p. 3480 - 3485
(2014/07/22)
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- Lab-in-a-shell: Encapsulating metal clusters for size sieving catalysis
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Here we describe a lab-in-a-shell strategy for the preparation of multifunctional core-shell nanospheres consisting of a core of metal clusters and an outer microporous silica shell. Various metal clusters (e.g., Pd and Pt) were encapsulated and confined in the void space mediated by the entrapped polymer dots inside hollow silica nanospheres acting first as complexing agent for metal ions and additionally as encapsulator for clusters, limiting growth and suppressing the sintering. The Pd clusters encapsulated in hybrid core-shell structures exhibit exceptional size-selective catalysis in allylic oxidations of substrates with the same reactive site but different molecular size (cyclohexene ~0.5 nm, cholesteryl acetate ~1.91 nm). The solvent-free aerobic oxidation of diverse hydrocarbons and alcohols was further carried out to illustrate the benefits of such an architecture in catalysis. High activity, outstanding thermal stability and good recyclability were observed over the core-shell nanocatalyst.
- Qiao, Zhen-An,Zhang, Pengfei,Chai, Song-Hai,Chi, Miaofang,Veith, Gabriel M.,Gallego, Nidia C.,Kidder, Michelle,Dai, Sheng
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supporting information
p. 11260 - 11263
(2014/10/15)
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- Semisynthesis and quantitative structure-activity relationship (QSAR) study of some cholesterol-based hydrazone derivatives as insecticidal agents
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In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, four series of novel cholesterol-based hydrazone derivatives were synthesized, and their insecticidal activity was tested against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1 mg/mL. All the derivatives showed the better insecticidal activity than their precursor cholesterol. Quantitative structure-activity relationship (QSAR) model demonstrated that six descriptors such as RDF085v, Mor06u, Mor11u, Dv, HATS0v and H-046, are likely to influence the insecticidal activity of these compounds. Among them, two important ones are the Mor06u and RDF085v.
- Yang, Chun,Shao, Yonghua,Zhi, Xiaoyan,Huan, Qu,Yu, Xiang,Yao, Xiaojun,Xu, Hui
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p. 4806 - 4812
(2013/09/02)
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- Synthesis and antimicrobial activity of novel oxysterols from lanosterol
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Chemically diverse oxysterols and their synthetic manipulations were carried out from variety of Δ8(9)-lanosterol derivatives and evaluated for their in vitro antimicrobial activities. Most of the synthesized oxysterols exhibited significant antifungal activity against the tested strains.
- Shingate, Bapurao B.,Hazra, Braja G.,Salunke, Deepak B.,Pore, Vandana S.,Shirazi, Fazal,Deshpande, Mukund V.
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p. 11155 - 11163
(2014/01/06)
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- Synthesis and biological studies of steroidal pyran based derivatives
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Steroid based cancer chemotherapeutic agents of the type 2′-amino-3′-cyanocholest-6-eno[5,7-de]4H-pyrans (1c-3c) have been synthesized and characterized by the various spectroscopic and analytical techniques. The DNA binding studies of compounds (1c-3c) with CT DNA were carried out by UV-vis and fluorescence spectroscopy and gel electrophoresis. The compounds (1c-3c) bind to DNA preferentially through electrostatic and hydrophobic interactions with Kb values found to be 5.4 × 103, 2.3 × 103 M-1 and 1.97 × 103 M-1, respectively indicating the higher binding affinity of compound (1c) towards DNA. The molecular docking study suggested that the electrostatic interaction of compounds (1c-3c) in between the nucleotide base pairs is due to the presence of pyran moiety in steroid molecule. All the compounds (1c-3c) cleave supercoiled pBR322 DNA via hydrolytic pathway, as validated by T4 DNA ligase assay. The compounds (1c-3c) were screened for in vitro cytotoxicity against the cancer and non-cancer cells SW480, A549, HepG2, HeLa, MCF-7, HL-60, DU-145, NL-20, HPC and HPLF by MTT assay. The compounds (1c-3c) were tested for genotoxicity (comet assay) involving apoptotic degradation of DNA and was analyzed by agarose gel electrophoresis and visualized by ethidium bromide staining. The results revealed that compound (1c) has better prospectus to act as cancer chemotherapeutic candidate which warrants further in vivo anticancer investigations.
- Shamsuzzaman,Dar, Ayaz Mahmood,Khan, Yusuf,Sohail, Aamir
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- Novel synthesis strategy for the preparation of individual phytosterol oxides
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Sterols (cholesterol and phytosterols) are important structural components of cell membranes and major constituents of lipid metabolism. Research on their oxides, such as the factors affecting oxidation, oxides' structures, and qualitative and quantitative analysis, aroused more attention in this decade. However, the biological roles of individual phytosterol oxides are still unclear because no commercial individual phytosterol oxide standards are available. Different from the traditional chemical synthesis, in the present study, chemical synthesis from a starting phytosterol mixture followed with a semipreparative HPLC separation produced individual oxides. TLC and analytical HPLC were used here to not only monitor the reaction process but also specifically analyze the synthetic intermediates and oxides. The chromatographic results exhibited strict rules and similar characteristics. Finally, for the first time, four individual phytosterol oxides were successfully separated and collected by a semipreparative HPLC system, thus providing a novel strategy for the preparation of individual phytosterol oxides.
- Gao, Junlan,Yue, Qiulin,Ji, Yishun,Cheng, Beijiu,Zhang, Xin
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p. 982 - 988
(2013/08/24)
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- Inhibitory effect of oxygenated cholestan-3-ol derivatives on the growth of Mycobacterium tuberculosis
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A variety of cholestan-3-ol derivatives, which are oxygenated at different positions of the steroid ring system, were prepared and tested for their inhibition of the Mycobacterium tuberculosis H37Rv strain. Several compounds showed significant antitubercular activities with MIC90 values in the range 4-8 μM and low or non-detectable toxicity against mammalian cells.
- Schmidt, Arndt W.,Choi, Taylor A.,Theumer, Gabriele,Franzblau, Scott G.,Kn?lker, Hans-Joachim
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p. 6111 - 6113
(2013/11/06)
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- Efficient selective oxidation of organic substrates using pyridinum sulfonate halochromate under solvent-free conditions and microwave irradiation: Experimental and theoretical study
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A convenient and rapid method has been developed for the selective oxidation of several types of alcohols to related carbonyl compounds under solvent-free conditions. In this study, the authors report the microwave-assisted selective oxidation of alcohols and a number of organic compounds with pyridinum sulfonate chlorochromate (PSCC) and pyridinum sulfonate fluorochromate (PSFC). The density functional theory calculations were made at B3LYP/6-31G* levels of theory and thermodynamic data supported the proposed mechanism involving formation of a halochromate ester, which showed that PSFC should be a more capable oxidant than PSCC. The oxidation products are easily obtained in short reaction time with good yields.
- Bekhradnia, Ahmad R.,Arshadi, Sattar
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experimental part
p. 705 - 710
(2012/08/08)
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- Synthesis of 7-dehydrocholesterol through hexacarbonyl molybdenum catalyzed elimination reaction
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The efficiency of hexacarbonyl molybdenum catalyzed elimination reaction of the allylic acetates has been improved by the presence of O,N- bis(trimethylsilyl) acetamide in the reaction medium. The methodology is particularly well employed for the elimination of 7-acetoxycholesterol-3- acetate(cholestrol-3,7-diacetate) for which the resulting product obtained was exclusively 5,7-homoannular diene(7-dehydrocholesterol-3-acetate). Good yield is achieved (up to 70 %) while decreasing the side products formation and reducing the costs as compared to the previously used procedures. Hexacarbonyl molybdenum elimination reaction is greatly influenced by the reaction temperature, at low as well as at high temperature low yield of the homoannular diene product is separated while at moderate conditions of temperature high products formation is observed.
- Ur Rahman, Faiz,Tan, Tian Wei
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p. 247 - 254
(2012/05/05)
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- Visible-light-induced metal-free allylic oxidation utilizing a coupled photocatalytic system of g-C3N4 and N-hydroxy compounds
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Graphitic carbon nitride (g-C3N4) and N-hydroxy compounds can function as a non-metal photocatalytic system to activate O 2 for the selective allylic oxidation under mild conditions, avoiding the employment of any metal derivative or organic oxidizing agents. Interestingly, the novel photocatalytic system affords a remarkably high selectivity towards the formation of aldehydes, especially in the oxidation of toluene. By combining the unique nature of g-C3N4 (surface basicity, semiconductor features, high stability) and the remarkable catalytic oxidation reactivity of nitroxyl radicals, this photocatalytic system opens up a mild and efficent access for C-H bond activation. Copyright
- Zhang, Pengfei,Wang, Yong,Yao, Jia,Wang, Congmin,Yan, Chao,Antonietti, Markus,Li, Haoran
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experimental part
p. 1447 - 1451
(2011/08/03)
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- An effective method for allylic oxidation of Δ5-steroids using tert-butyl hydroperoxide
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"Chemical equation presented" An allylic oxidation method for Δ5-steroids using TBHP as oxidant with a 2-quinoxalinol salen Cu(II) complex as catalyst is reported. A variety of Δ5- steroidal substrates are selectively oxidized to the corresponding enones. Excellent yields are achieved (up to 99% under optimized conditions) while significantly reducing reaction times required as compared to other current methods.
- Li, Yuancheng,Wu, Xianghong,Lee, Tae Bum,Isbell, Eleanor K.,Parish, Edward J.,Gorden, Anne E. V.
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experimental part
p. 1807 - 1810
(2010/05/17)
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- An unprecedented method for the generation of tert -butylperoxy radical using DIB/TBHP protocol: Solvent effect and application on allylic oxidation
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Figure presented Tert-Butylperoxy radical was generated with PhI(OAc) 2 and tBuOOH. Ester solvent was found to be critical and the protocol was applied in the allylic oxidation of various olefinic substrates, which gave the corresponding α,β-unsaturated enones in good yield and regioselectivity.
- Zhao, Yi,Yeung, Ying-Yeung
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supporting information; experimental part
p. 2128 - 2131
(2010/08/05)
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- Sterols as anticancer agents: Synthesis of ring-B oxygenated steroids, cytotoxic profile, and comprehensive SAR analysis
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The cytotoxicity of oxysterols was systematically studied in tumor and normal cells. Synthetic strategies to prepare this library included oxidations at ring B and a new method to yield 6β-hemiphthalates directly from Δ5-steroids. Most oxysterols were cytotoxic and showed selectivity toward cancer cells, LAMA-84 cells (leukemia) being particularly sensitive to 4, 8, 22, and 27 (IC50 5.6 μM). The structural requirements to induce selective toxicity are discussed to shed light on the development of new anticancer drugs.
- Carvalho, Jo?o F. S.,Silva, M. Manuel Cruz,Moreira, Jo?o N.,Sim?es, Sérgio,Sá E Melo, M. Luisa
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supporting information; experimental part
p. 7632 - 7638
(2011/02/21)
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- An environmentally benign catalytic oxidation of cholesteryl acetate with molecular oxygen by using N-hydroxyphthalimide
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A green and effective method is reported for the oxidation of cholesteryl acetate to 7-keto-cholesteryl acetate with O2 in the presence of catalytic amounts of N-hydroxyphthalimide (NHPI) under mild conditions. It was found that Co(OAc)2 could cooperate with Mn(OAc)2 to enhance the catalytic ability of NHPI resulting in better yields. This economical and environmentally-friendly method provides a potentially new way for the synthesis of the intermediate product of vitamin D3 in industry, which eliminates the use of large amounts of bromine in present route and overcomes the drawbacks of the known oxidation methods.
- Yao, Zhen,Hu, Xingbang,Mao, Jianyong,Li, Haoran
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experimental part
p. 2013 - 2017
(2010/06/19)
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- Synthesis and evaluation of some steroidal oximes as cytotoxic agents: Structure/activity studies (I)
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The side chain of a compound plays an important role in its biological function. In our studies, we have found that hydroximinosteroid derivatives with different side chains and position of hydroximino on ring A and B displayed remarkable distinct cytotoxicities against a diversity of cancer cell types. Presence of an oxime group on ring B and a hydroxy on ring A or B resulted in a higher cytotoxicity than other structural motifs. In addition, a cholesterol-type side chain at position 17 was required for the biological activity. Our findings provide new evidence showing the relationship between the chemical structure and biological function. The information obtained from the studies may be useful for the design of novel chemotherapeutic drugs.
- Cui, Jian-Guo,Fan, Lei,Huang, Li-Liang,Liu, Hong-Li,Zhou, Ai-Min
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experimental part
p. 62 - 72
(2009/04/10)
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- Efficient chemoenzymatic synthesis, cytotoxic evaluation, and SAR of epoxysterols
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A library of diastereomerically pure epoxysterols, prepared by combining chemical and enzymatic methodologies, was evaluated for cytotoxicity toward human cancer and noncancer cell lines. Unsaturated steroids were oxidized by magnesium bis(monoperoxyphthalate) hexahydrate in acetonitrile, and the resulting epimeric epoxides were enzymatically separated using Novozym 435 or lipase AY. Some of the synthesized epoxysterols have potent cytotoxicity and higher activity on cancer cell lines HT29 and LAMA-84.
- Carvalho, Jo?o F. S.,Cruz Silva, M. Manuel,Moreira, Jo?o N.,Sim?es, Sérgio,Sá E Melo, M. Luisa
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experimental part
p. 4007 - 4019
(2009/12/26)
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- Allylic Oxidations Catalyzed by Dirhodium Catalysts under Aqueous Conditions
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The present invention relates to compositions and methods for achieving the efficient allylic oxidation of organic molecules, especially olefins and steroids, under aqueous conditions. The invention concerns the use of dirhodium (II,II) “paddlewheel complexes, and in particular, dirhodium carboximate and tert-butyl hydroperoxide as catalysts for the reaction. The use of aqueous conditions is particularly advantageous in the allylic oxidation of 7-keto steroids, which could not be effectively oxidized using anhydrous methods, and in extending allylic oxidation to enamides and enol ethers.
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Page/Page column 22
(2009/04/24)
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- J-based analysis and DFT-NMR assignments of natural complex molecules: Application to 3β,7-dihydroxy-5,6-epoxycholestanes
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In order to reproduce the stereochemical dispositions of the epoxy and hydroxy functionalities, four 3β,7-hydroxy-5,6-epoxycholestanes were easily prepared from cholesterol, and their NMR spectroscopic data were experimentally obtained from 1D and 2D NMR experiments. An exhaustive QM-J-based analysis was then performed to replicate the experimental H-H and C-H coupling constants as well as the 13C NMR chemical shifts. The B3LYP GIAO methodology with the 6-311-G(d,p) basis set was chosen and showed that the data obtained from rings A and B were sufficient to calculate the correct stereochemistry of the 5,6-epoxy and 7-hydroxy groups. Wiley-VCH Verlag GmbH & Co. KGaA, 2008.
- Poza, Jesus Javier,Jimenez, Carlos,Rodriguez, Jaime
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experimental part
p. 3960 - 3969
(2009/04/08)
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- Synthesis and in vitro antibacterial activity of new steroidal thiosemicarbazone derivatives
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We investigated the antibacterial activity of some new steroidal thiosemicarbazone derivatives, prepared from the reaction of cholest-5-en-7-one with thiosemicarbazides, in ethanol in the presence of a few drops of HCl at 80 °C in high yield. All the compounds have been characterized by means of elemental analyses, IR, 1H NMR and mass spectroscopic data, to find an effective antibacterial agent. The antibacterial activity was first tested in vitro by the disk diffusion assay against two Gram-positive and two Gram-negative bacteria, and then the minimum inhibitory concentration (MIC) of compounds was determined. The results showed that the steroidal thiosemicarbazones derivatives inhibit growth of both types of the bacteria (Gram-positive and Gram-negative). The acetoxy and chloro derivatives of cyclopentyl and cyclohexyl amine thiosemicarbazones were found to have more antibacterial activity than the other derivatives.
- Khan, Salman Ahmad,Kumar, Praveen,Joshi, Rajkumar,Iqbal, Prince F.,Saleem, Kishwar
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p. 2029 - 2034
(2008/12/22)
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- Optimal TBHP allylic oxidation of Δ5 - Steroids catalyzed by dirhodium caprolactamate
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Dirhodium caprolactamate is the most efficient catalyst for the oxidation of Δ5-steroids to 7-keto-Δ5-steroids by 70% tert-butyl hydroperoxide in water (T-HYDRO). Isolated product yields range from 38 to 87%.
- Choi, Hojae,Doyle, Michael P.
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p. 5349 - 5352
(2008/09/17)
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- Synthesis and evaluation of new 6-hydroximinosteroid analogs as cytotoxic agents
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Taking into account the structural requirements for cytotoxicity, several new hydroximinosteroid derivatives have been prepared and evaluated for their cytotoxic activity against A-549, H116, PSN1, and T98G cultured tumor cell lines in order to obtain further information on the potential pharmacophoric core of this type of compound. The influence of the oxygenated position in the A ring, the presence of an additional oxygenated position at C-7 and C-16, and a fluorinated position at C-5 were considered in order to study the structure-activity relationships. The results reveal the importance of oxygenated positions in the A ring (e.g., 4,5-epoxide showed an IC50 value against HCT-116 under micromolar level) for an increase in cytotoxic activity in this type of compound. Furthermore, they showed an important selectivity toward colon tumor line (HCT-116).
- Poza, Javier,Rega, Miriam,Paz, Vanessa,Alonso, Beatriz,Rodriguez, Jaime,Salvador, Nelida,Fernandez, Antonio,Jimenez, Carlos
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p. 4722 - 4740
(2008/03/13)
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- Allylic and benzylic oxidation reactions with sodium chlorite
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Various allylic and benzylic substrates were selectively oxidized to the corresponding enones in good yields using sodium chlorite, either in combination with tert-butyl hydroperoxide in stoichiometric conditions, or associated with N-hydroxyphthalimide as catalyst. These oxidation reactions were effectively and economically performed under mild, transition-metal free conditions and therefore the dual challenge of cost effectiveness and benign nature of the processes was met with.
- Silvestre, Samuel M.,Salvador, Jorge A.R.
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p. 2439 - 2445
(2007/10/03)
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- Mild manganese(III) acetate catalyzed allylic oxidation: Application to simple and complex alkenes
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Manganese(III) acetate catalyzed allylic oxidation of alkenes to the corresponding enones was investigated, showing excellent regioselectivity and chemoselectivity (functional group compatibility). Δ5-Steroids were transformed into bioactive Δ5-en-7-ones under a nitrogen atmosphere, whereas simple alkenes were converted into the corresponding enones under an oxygen atmosphere in good yields.
- Shing, Tony K. M.,Yeung, Ying-Yeung,Su, Pak L.
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p. 3149 - 3151
(2007/10/03)
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- A new electrochemical system for stereoselective allylic hydroxylation of cholesteryl acetate with dioxygen induced by iron picolinate complexes
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The oxygenation reaction of cholesteryl acetate 1 was examined with the FeIII(PA)3/O2/MeCN system using an electrochemical method. The constant potential technique gave mainly the 7-hydroxylated product stereoselectively, along with the 7-oxo product. This oxygenation system is mechanistically unique, requiring iron catalyst, dioxygen, and both cathode and anode.
- Okamoto, Iwao,Funaki, Wataru,Nakaya, Kyosuke,Kotani, Eiichi,Takeya, Tetsuya
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p. 756 - 759
(2007/10/03)
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