- Improved large mesoporous ordered molecular sieves - Stabilization and acid/base functionalization
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The preparation of nanoporous materials with enhanced stability using an improved synthesis route using reactive inorganic silica and alumina species is reported. This way improved mesoporous molecular sieves were obtained. The synthesized aluminum substituted mesoporous molecular materials (Al-MMS) contain very large pores of 50-200? size combined with an improved pore wall thickness. Increased wall thickness and Al substitution lead to an improved chemical stability against alkaline solution. The textural, structural and acid properties are investigated by physico-chemical methods. The catalytic performance acidic materials was tested in the benzoylation reaction; amino functionalized materials were studied in the base catalyzed Michael addition.
- Kosslick, Hendrik,Pitsch, Irene,Deutsch, Jens,Pohl, Marga-Martina,Schulz, Axel,Tuan, Vu Anh,Tuyen, Nguyen Dinh,Frunza, Ligia,Jaeger, Christian
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Read Online
- Identification of Inhibitors of Cholesterol Transport Proteins Through the Synthesis of a Diverse, Sterol-Inspired Compound Collection
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Cholesterol transport proteins regulate a vast array of cellular processes including lipid metabolism, vesicular and non-vesicular trafficking, organelle contact sites, and autophagy. Despite their undoubted importance, the identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol-binding site. Herein we report a general strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of a diverse sterol-inspired compound collection. Fusion of a primary sterol fragment to an array of secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster-C, which displayed a surprising preference for the unnatural-sterol AB-ring stereochemistry and new inhibitors of Aster-A. We propose that this strategy can and should be applied to any therapeutically relevant sterol-binding protein.
- Laraia, Luca,Olsen, Asger Hegelund,Whitmarsh-Everiss, Thomas
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supporting information
p. 26755 - 26761
(2021/11/17)
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- Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion
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Glucocorticoids (GCs) are widely used in medicine for their role in the treatment of autoimmune-mediated conditions, certain cancers, and organ transplantation. The transcriptional activities GCs elicit include transrepression, postulated to be responsible for the anti-inflammatory activity, and transactivation, proposed to underlie the undesirable side effects associated with long-term use. A GC analogue that could elicit only transrepression and beneficial transactivation properties would be of great medicinal value and is highly sought after. In this study, a series of 1-(4-substituted phenyl)pyrazole-based GC analogues were synthesized, biologically screened, and evaluated for SARs leading to the desired activity. Activity observed in compounds bearing an electron deficient arylpyrazole moiety showed promise toward a dissociated steroid, displaying transrepression while having limited transactivation activity. In addition, compounds 11aa and 11ab were found to have anti-inflammatory efficacy comparable to that of dexamethasone at 10 nM, with minimal transactivation activity and no reduction of insulin secretion in cultured rat 832/13 beta cells.
- Burke, Susan J.,Campagna, Shawn R.,Collier, J. Jason,Dunlap, Lee E.,Fisch, Alexander R.,Kennedy, Brandon J.,Kirkland, Justin K.,Lato, Ashley M.,Prevatte, Carson W.,Smith, Russell T.,Vogiatzis, Konstantinos D.
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p. 1568 - 1577
(2021/10/04)
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- Chemoselective Oxidation of Equatorial Alcohols with N-Ligated λ3-Iodanes
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The site-selective and chemoselective functionalization of alcohols in complex polyols remains a formidable synthetic challenge. Whereas significant advancements have been made in selective derivatization at the oxygen center, chemoselective oxidation to the corresponding carbonyls is less developed. In cyclic systems, whereas the selective oxidation of axial alcohols is well known, a complementary equatorial selective process has not yet been reported. Herein we report the utility of nitrogen-ligated (bis)cationic λ3-iodanes (N-HVIs) for alcohol oxidation and their unprecedented levels of selectivity for the oxidation of equatorial over axial alcohols. The conditions are mild, and the simple pyridine-ligated reagent (Py-HVI) is readily synthesized from commercial PhI(OAc)2 and can be either isolated or generated in situ. Conformational selectivity is demonstrated in both flexible 1,2-substituted cyclohexanols and rigid polyol scaffolds, providing chemists with a novel tool for chemoselective oxidation.
- Mikhael, Myriam,Adler, Sophia A.,Wengryniuk, Sarah E.
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supporting information
p. 5889 - 5893
(2019/08/26)
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- Synthesis of the Tetracyclic Structure of Batrachotoxin Enabled by Bridgehead Radical Coupling and Pd/Ni-Promoted Ullmann Reaction
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The steroidal ABCD-ring system of the potent neurotoxin batrachotoxin was efficiently assembled in a convergent fashion. Bridgehead radical coupling between the simple AB-ring and D-ring fragments (3 and 4) formed the sterically congested linkage at the C9-oxygen-attached tetrasubstituted carbon. The C-ring was then cyclized by the Pd/Ni-promoted Ullmann reaction of the vinyl triflate and vinyl bromide of 19, giving rise to tetracyclic structure 1.
- Sakata, Komei,Wang, Yinghua,Urabe, Daisuke,Inoue, Masayuki
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supporting information
p. 130 - 133
(2018/01/17)
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- Total Synthesis of ent-Pregnanolone Sulfate and Its Biological Investigation at the NMDA Receptor
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A unique asymmetric total synthesis of the unnatural enantiomer of pregnanolone, as well as a study of its biological activity at the NMDA receptor, is reported. The asymmetry is introduced by a highly atom-economic organocatalytic Robinson annulation. A new method for the construction of the cyclopentane D-ring consisting of CuI-catalyzed conjugate addition and oxygenation followed by thermal cyclization employing the persistent radical effect was developed. ent-Pregnanolone sulfate is surprisingly only 2.6-fold less active than the natural neurosteroid.
- Kapras, Vojtech,Vyklicky, Vojtech,Budesinsky, Milos,Cisarova, Ivana,Vyklicky, Ladislav,Chodounska, Hana,Jahn, Ullrich
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supporting information
p. 946 - 949
(2018/02/23)
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- Lipase-catalyzed domino Michael-aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone for the synthesis of bicyclic compounds
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Synthesis of bicyclic compounds was achieved via a lipase-catalyzed, stereoselective, domino Michael-aldol reaction of 2-methyl-1,3-cycloalkanedione and methyl vinyl ketone. Appropriate reaction conditions, including the type of enzyme, solvent, and temperature, were determined. In addition, the effects of solvent polarity and addtives were investigated. The reaction proceeded in the presence of lipase AS in a solution of 20% acetone in dimethylsulfoxide (DMSO) at 10 °C for 8 days, followed by the addition of p-toluenesulfonic acid (TsOH) to afford bicyclic compounds in 51-83% yields with moderate stereoselectivity. Although this domino Michael-aldol reaction showed only moderate stereoselectivity, even with the acid-supported enhancement of the reaction, these results represent potential new applications for lipase.
- Sano, Kaoru,Kohari, Yoshihito,Nakano, Hiroto,Seki, Chigusa,Takeshita, Mitsuhiro,Tokiwa, Micho,Hirose, Yoshihiko,Uwai, Koji
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supporting information
p. 46 - 54
(2016/01/09)
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- Synthesis of the ABC skeleton of the aglycon of Echinoside A
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Echinoside A is a triterpene saponin isolated from the sea cucumber Actinopyga echinites (JAEGER), which displays potent antitumor activities in vitro and in vivo. Here, we report the synthesis of the ABC-fused ring skeleton of the aglycon of Echinoside A, with the enantiomerically pure (+)-Wieland-Miescher ketone being used as starting material and a Robinson annulation as the key reaction.
- Yu, Jun,Yu, Biao
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p. 1331 - 1335
(2015/10/28)
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- Novel supported and unsupported prolinamides as organocatalysts for enantioselective cyclization of triketones
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A novel prolylsulfonamide derived from ethylene diamine and its supported counterpart has been prepared and tested as enantioselective intramolecular aldol reaction of cyclic and acyclic triketones. Good to excellent yields and enantioselectivities have been obtained in water and under solvent free conditions.
- Pedrosa, Rafael,Andrés, José María,Manzano, Rubén,Pérez-López, César
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supporting information
p. 3101 - 3104
(2013/06/27)
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- Recyclable L-proline organocatalyst for Wieland-Miescher ketone synthesis
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Wieland-Miescher ketone 4 was synthesised using L-proline catalyst in the ionic liquid medium via non-selective conjugated addition reaction followed by an enantioselective intermolecular Aldol condensation reaction of triketone 3 intermediate. Short reaction time, recycling of the catalyst, good yield and selectivity are major outcomes of this proposed protocol. Indian Academy of Sciences.
- Srivastava, Vivek
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p. 1523 - 1527
(2014/04/03)
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- Recoverable silica-gel supported binam-prolinamides as organocatalysts for the enantioselective solvent-free intra- and intermolecular aldol reaction
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Silica-gel supported binam-derived prolinamides are efficient organocatalysts for the direct intramolecular and intermolecular aldol reaction under solvent-free conditions using conventional magnetic stirring. These organocatalysts in combination with benzoic acid showed similar results to those obtained under similar homogeneous reaction conditions using an organocatalyst of related structure. For the intermolecular process, the aldol products were obtained at room temperature and using only 2 equiv of the ketone with high yields, regio-, diastereo- and enantioselectivities. Under these reaction conditions, also the cross aldol reaction between aldehydes is possible. The recovered catalyst can be reused up to nine times providing similar results. More interestingly, these heterogeneous organocatalysts can be used in the intramolecular aldol reaction allowing the synthesis of the Wieland-Miescher and ketone analogues with up to 92% ee, with its reused being possible up to five times without detrimental on the obtained results.
- Ba?ón-Caballero, Abraham,Guillena, Gabriela,Nájera, Carmen,Faggi, Enrico,Sebastián, Rosa María,Vallribera, Adelina
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p. 1307 - 1315
(2013/02/23)
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- A practical protocol for asymmetric synthesis of wieland-miescher and hajos-parrish ketones catalyzed by a simple chiral primary amine
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This article describes a simple chiral primary amine catalyzed efficient and practical protocol for the large-scale synthesis of Wieland-Miescher and Hajos-Parrish ketones as well as their analogues. Georg Thieme Verlag Stuttgart. New York.
- Xu, Changming,Zhang, Long,Zhou, Pengxin,Luo, Sanzhong,Cheng, Jin-Pei
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p. 1939 - 1945
(2013/07/26)
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- Asymmetric synthesis of Wieland-Miescher and Hajos-Parrish ketones catalyzed by an amino-acid-derived chiral primary amine
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This paper describes a simple chiral primary amine-catalyzed highly efficient and practical protocol for the synthesis of both Wieland-Miescher ketone and Hajos-Parrish ketone as well as their analogues. The reaction can be conducted in gram scale with 1%
- Zhou, Pengxin,Zhang, Long,Luo, Sanzhong,Cheng, Jin-Pei
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experimental part
p. 2526 - 2530
(2012/05/05)
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- Enantioselective synthesis of a taxol C ring
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An enantioselective synthesis of a C ring of taxol has been accomplished. The key step is an oxidative cleavage of a derivative of the Wieland-Miescher ketone. A first attempt of a Shapiro reaction modelling the coupling of the C ring with the A fragment of taxol was also successful.
- Ma, Cong,Schiltz, Stephanie,Prunet, Joelle
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experimental part
p. 1579 - 1594
(2012/05/19)
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- Efficient solvent-free robinson annulation protocols for the highly enantioselective synthesis of the wieland-miescher ketone and analogues
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A highly efficient (93% overall yield) and enantioselective (94% ee) synthesis of the WielandMiescher ketone (10-g scale) through a solvent-free Robinson annulation procedure is reported. The process involves only 1 mol% triethylamine as the base in the initial Michael process and the organocatalyst N-tosyl-(Sa)-binam-L-prolinamide (2mol%) and benzoic acid (0.5 mol% ) for the intramolecular aldol process. This green protocol is applied to a wide range of valuable building block analogues of the Wieland-Miescher ketone (10 examples). Among these, a noteworthy compound for terpene synthesis is the 8a-allyl derivative, which is prepared in 93% yield and 97% ee in a process allowing the recovery and reutilization of the organocatalyst. Furthermore, a one-pot, two-step process has also been developed.
- Bradshaw, Ben,Etxebarria-Jardi, Gorka,Bonjoch, Josep,Viozquez, Santiago F.,Guillena, Gabriela,Najera, Carmen
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experimental part
p. 2482 - 2490
(2009/12/29)
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- Base Stable Ionic Liquids
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The present invention relates to novel base stable ionic liquids and uses thereof as solvents in chemical reactions, especially base catalysed chemical reactions and reactions comprising the use of strong basis.
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Page/Page column 10
(2009/09/07)
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- Synthesis of a dysidiolide-inspired compound library and discovery of acetylcholinesterase inhibitors based on protein structure similarity clustering (PSSC)
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Biologically relevant compound collections are a major prerequisite for efficient protein ligand development and ultimately for drug discovery. We herein describe the development of a compound collection inspired by the decalin core motif of two natural products, dysidiolide 1 and sulfiricin 2, both inhibitors of the Cdc25A phosphatase. Several keto-functionalized decalinols were synthesized in solution, immobilized on Merrifield resin equipped with a dihydropyranyl linker, and then subjected to aldol condensation reactions with different aldehydes leading to exocyclic E-configured olefins. Further diversity-increasing transformations on the solid support included Sonogashira, Suzuki, and Heck reactions, Cu-catalyzed conjugate addition and Grignard reactions, alkylation reactions in the α-position to a ketone, Wittig reactions, and reductive animations. In total, 483 compounds were synthesized. Cdc25A and AChE exhibit structural similarity in their ligand-sensing cores and were thus grouped into a protein structure similarity cluster (PSSC). A screen for AChE inhibition of a subset of 162 compounds yielded three micromolar inhibitors of AChE with IC50 values 20 μM.
- Scheck, Michael,Koch, Marcus A.,Waldmann, Herbert
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p. 4792 - 4802
(2008/09/21)
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- Combining multi-catalysis and multi-component systems for the development of one-pot asymmetric reactions: Stereoselective synthesis of highly functionalized bicyclo[4.4.0]decane-1,6-diones
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We have developed a direct amine/acid-catalyzed stereoselective hydrogenation of a variety of Wieland-Miescher (W-M) ketones, Hajos-Parrish (H-P) ketones and their analogs with organic hydrides (Hantzsch esters) as the hydrogen source. This astonishingly simple and biomimetic approach was used to construct highly functionalized chiral bicyclo[4.4.0]decane-1,6-diones 6 in a diastereoselective fashion. This is an example of the development of a new technology by the combination of multiple catalysts and components in one pot to deliver highly functionalized chiral molecules. The Royal Society of Chemistry 2008.
- Ramachary, Dhevalapally B.,Sakthidevi, Rajasekar
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supporting information; experimental part
p. 2488 - 2492
(2009/02/02)
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- INTERLEUKIN-1 AND TUMOR NECROSIS FACTOR-A MODULATORS; SYNTHESES OF SUCH MODULATORS AND METHODS OF USING SUCH MODULATORS
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Compounds are disclosed that have the chemical structure of Formula (II), (IIA) and (IIB) and their prodrug esters and acid-addition salts, and that are useful as Interleukin-1 and Tumor Necrosis Factor-a modulators, and thus are useful in the treatment of various diseases, wherein the R groups are defined in the claims.
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Page/Page column 120; Sheet 4/69; 10/69
(2010/11/25)
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- Evaluating β-amino acids as enantioselective organocatalysts of the Hajos-Parrish-Eder-Sauer-Wiechert reaction
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A systematic study of the effect of substitution within the β-amino acid framework indicates that both β2- and β3- amino acids catalyse the Hajos-Parrish-Eder-Sauer-Wiechert reaction with poor to reasonable levels of enantioselectivity. These results led to the evaluation of the conformationally constrained β-amino acid (1R,2S)-cispentacin, which catalyses the Hajos-Parrish-Eder-Sauer-Wiechert reaction with comparable or higher levels of enantioselectivity to l-proline. The Royal Society of Chemistry.
- Davies, Stephen G.,Russell, Angela J.,Sheppard, Ruth L.,Smith, Andrew D.,Thomson, James E.
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p. 3190 - 3200
(2008/03/14)
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- Benzimidazole-pyrrolidine/H+ (BIP/H+), a highly reactive organocatalyst for asymmetric processes
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A new chiral benzimidazole-pyrrolidine has been devised, which exhibits excellent activities in aminocatalyzed aldol reactions, leading to aldol products in high yields and enantioselectivities in the presence of an equimolar amount of a Broensted acid. This organocatalyst has demonstrated remarkable reactivities in aldol processes even with equimolar amounts of aldehyde and ketone in THF. A discussion of the role of the Broensted acid as a co-catalyst is provided along with some applications of this new class of organocatalyst in Robinson annelation and α-amination processes. Wiley-VCH Verlag GmbH & Co. KGaA, 2007.
- Lacoste, Eric,Vaique, Emilie,Berlande, Muriel,Pianet, Isabelle,Vincent, Jean-Marc,Landais, Yannick
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p. 167 - 177
(2007/10/03)
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- DECALINE-DERIVED COMPOUNDS AS PHARMACEUTICALLY ACTIVE AGENTS
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The present invention relates to compounds having a decaline scaffold, pharmaceutically acceptable salts of these compounds and pharmaceutical compositions containing at least one of these compounds togehter with pharmaceutically acceptable carrier, excipient and/or diluents. Said decaline-derived compounds can be used for prophylaxsis and/or treatment of diabetes mellitus type I, diabetes mellitus type II, tuberculosis and other infectious diseases, proliferative diseases, cancer, neurodegenerative diseases, obesity, cognitive dysfunctions and metabolic syndromes.
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Page/Page column 63-64
(2008/06/13)
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- New magnesium oxide fluorides with hydroxy groups as catalysts for Michael additions
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Amorphous materials - magnesium oxide fluoride with hydroxy groups - of high surface area were prepared for the first time by a soft sol-gel method involving initial fluorination and subsequent hydrolysis of the fluorinated gel. Their structural propertie
- Prescott, Hillary A.,Li, Zhi-Jian,Kemnitz, Erhard,Deutsch, Jens,Lieske, Heiner
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p. 4616 - 4628
(2007/10/03)
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- Application of calcined Mg-Al hydrotalcites for Michael additions: An investigation of catalytic activity and acid-base properties
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Mg-Al hydrotalcite catalysts with different Mg/Al molar ratios (0.6, 1.4, 2.2, 3.0) were calcined and tested in liquid-phase Michael additions at room temperature. The catalysts and pure oxides (MgO and Al2O 3) were characterized by
- Prescott, Hillary A.,Li, Zhi-Jian,Kemnitz, Erhard,Trunschke, Annette,Deutsch, Jens,Lieske, Heiner,Auroux, Aline
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p. 119 - 130
(2007/10/03)
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- Promotion of one-pot Robinson annelation achieved by gradual pressure and temperature manipulation under supercritical conditions
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The one-pot Robinson annelation from 2-methyl-cyclohexane-1,3-dione with 3-buten-2-one can be achieved in high yield (95%) and high selectivity (95%) by pressure and temperature manipulation using supercritical carbon dioxide in the presence of MgO catalyst, whose method could be applied for various ketones to synthesize fused polycyclic compounds.
- Kawanami, Hajime,Ikushima, Yutaka
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p. 5147 - 5150
(2007/10/03)
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- Interleukin-1 and tumor necrosis factors-α modulators, syntheses of said modulators and methods of using modulators
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Novel compounds are disclosed that have the chemical structure of Formula (IIB), and its prodrug esters and acid-addition salts, and that are useful as Interleukin-1 and Tumor Necrosis Factor-α modulators, and thus are useful in the treatment of various d
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Page column 27
(2008/06/13)
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- A proline-catalyzed asymmetric Robinson annulation reaction
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A single-step enantioselective synthesis of the Wieland-Miescher ketone (5) is presented. We show that L-proline as well as a number of other chiral amines can act as catalysts of both steps of the Robinson annulation reaction. Other chiral amines are identified as catalysts of Michael and aldol addition reactions. (C) 2000 Elsevier Science Ltd.
- Bui,Barbas III
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p. 6951 - 6954
(2007/10/03)
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- Efficient Preparation of Optically Pure Wieland-Miescher Ketone and Confirmation of Its Absolute Stereochemistry by the CD Exciton Chirality Method
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An efficient preparation procedure of optically pure Wieland-Miescher ketone, (8aR)-(-)-3.4.8.8a-tetrahydro-8a-methyl-1.6(2H.7H)-naphthalenedione (1), is described, and its absolute stereochemistry is confirmed by the application of the CD exciton chirali
- Harada, Nobuyuki,Sugioka, Tatsuo,Uda, Hisashi,Kuriki, Takeo
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- Ring Cleavage of Cyclohexane-1,3-diones in the Aldol Cyclization Step of Robinson Annelations: A Novel Mechanism via Oxa-Twistanes and δ-Lactones
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The pyrrolidine-induced aldol cyclization of methyl 2-methyl-2-(3-oxobutyl)-1,3-dioxocyclohexane-4-acetate (1) afforded methyl 1,2,3,4,6,7,8,8a-octahydro-8a-methyl-1,6-dioxonaphthalene-2-acetate (13) rather than undergoing lactonization-directed closure in the opposite sense.Mild base-induced cyclization of 1 with sodium methoxide in methanol or 1,8-diazabicycloundec-7-ene (DBU) in tetrahydrofuran (THF) effected cleavage of the cyclohexane-1,3-dione ring, giving mainly cyclohexenone acid 14a (2-(1,4-dimethyl-3-oxo-1-cyclohexen-2-ylmethyl)butanedioic acid monomethyl ester) and δ-lactone 15 (methyl (4aβ,8aβ)-octahydro-6,8a-dimethyl-2,5-dioxo-2H-1-benzopyran-4a-acetate).Prolonged exposure of 15 to sodium methoxide in methanol yielded mixtures of acyclic diester 17 and the isomeric γ-lactone 18 presumably via lactone methanolysis to ketol diester 16 followed by retroaldol ring opening or relactonization onto the acetate ester.The structure and stereochemistry of 18 were established by X-ray crystallography (Figure 1).Similar aldol cyclizations of 2-methyl-2-(3-oxobutyl)-1,3-cyclohexanedione (19) and its 4-methyl analogue (11) with sodium methoxide in methanol or DBU in THF afforded cyclohexenone acids 20a and 22a, respectively, the latter accompanied by δ-lactone 23.Bridged ketols 21 (from 19) and 24 and 25 (from 11) were also isolated from the reactions with DBU.A novel mechanism (Scheme I) involving bridging aldol cyclization to endo ketols (27 and 30), intramolecular hemiketal formation to oxatwistanones (28 and 31), ring cleavage to δ-lactones (29 and 32), and β-elimination of the δ-lactones having an available α-hydrogen to cyclohexenone acids is proposed to explain the formal retro-Claisen transformations in the absence of an external nucleophile (DBU/THF) and the apparent hydrolyses under anhydrous conditions.
- Muskopf, Jack W.,Coates, Robert M.
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- Organic Reactions at High Pressure. A Robinson Annulation Sequence Initiated by Michael Addition of Activated Cycloalkanones with Hindered Enones
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Activated cycloalkanones (ring size = five, six, seven) undergo Michael addition to β,β-disubstituted enones and subsequent aldol cyclization at 15 kbar (1.5 GPa) pressure in acetonitrile containing triethylamine or 1,5-diazabicyclonon-5-ene to aff
- Dauben, William G.,Bunce, Richard A.
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p. 4642 - 4648
(2007/10/02)
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