- Computational chemical analysis of Ru(II)-Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions
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Computational chemical analysis of Ru(II)-Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions was performed using density functional theory (DFT). In this study, cyclopropane ring–fused γ-lactones, which are 5.8?kcal/mol more stable than the corresponding minor enantiomer, are obtained as the major product. The results of the calculations suggest that the enantioselectivity of the Ru(II)-Pheox–catalyzed intramolecular cyclopropanation reaction is affected by the energy differences between the starting structures 5l and 5i. The reaction pathway was found to be a stepwise mechanism that proceeds through the formation of a metallacyclobutane intermediate. This is the first example of a computational chemical analysis of enantioselective control in an intramolecular carbene-transfer reaction using C1-symmetric catalysts.
- Nakagawa, Yoko,Nakayama, Naofumi,Goto, Hitoshi,Fujisawa, Ikuhide,Chanthamath, Soda,Shibatomi, Kazutaka,Iwasa, Seiji
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Read Online
- Calix[4]arene-Modified Oligosiloxane as a Quasi-Immobilized Neutral Carrier for Silicone-Rubber-Membrane Sodium Ion-Selective Electrodes
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An oligo(dimethylsiloxane) carrying ionophorous calix[4]arene moieties at the side chain was synthesized as a Na+ neutral carrier for highly durable silicone-ruhher membranes of ion-selective electrodes by reacting calix[4]arene tetraallyl ester with an oligo(methylsiloxane). This medium-molecular-weight calix[4]arene ionophore alleviated the drawback of chemically-modified calixarene-based silicone-rubber membranes, such as a high membrane impedance and a slow electrode response.
- Kimura, Keiichi,Tsujimura, Yutaka,Yokohama, Masaaki,Maeda, Takumi
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Read Online
- Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with Enhanced Selectivity
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Subtype selectivity represents a challenge in many drug discovery campaigns. A typical example is the FK506 binding protein 51 (FKBP51), which has emerged as an attractive drug target. The most advanced FKBP51 ligands of the SAFit class are highly selective vs. FKBP52 but poorly discriminate against the homologs and off-targets FKBP12 and FKBP12.6. During a macrocyclization pilot study, we observed that many of these macrocyclic analogs have unanticipated and unprecedented preference for FKBP51 over FKBP12 and FKBP12.6. Structural studies revealed that these macrocycles bind with a new binding mode featuring a transient conformation, which is disfavored for the small FKBPs. Using a conformation-sensitive assay we show that this binding mode occurs in solution and is characteristic for this new class of compounds. The discovered macrocycles are non-immunosuppressive, engage FKBP51 in cells, and block the cellular effect of FKBP51 on IKKα. Our findings provide a new chemical scaffold for improved FKBP51 ligands and the structural basis for enhanced selectivity.
- Bajaj, Thomas,Bracher, Andreas,Charalampidou, Anna,Gassen, Nils C.,Geiger, Thomas M.,Hausch, Felix,Heymann, Tim,Kolos, Jürgen,Merz, Stephanie,Meyners, Christian,Purder, Patrick L.,Taubert, Martha C.,Voll, Andreas M.,Wessig, Pablo
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supporting information
p. 13257 - 13263
(2021/05/07)
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- Synthesis and cytotoxicity evaluation of DOTA-conjugates of ursolic acid
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In this study, we report the synthesis of several amine-spacered conjugates of ursolic acid (UA) and 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA). Thus, a total of 11 UA-DOTA conjugates were prepared holding various oligo-methylene diamine spacers as well as different substituents at the acetate units of DOTA including tert-butyl, benzyl, and allyl esters. Furthermore, three synthetic approaches were compared for the ethylenediamine-spacered conjugate 29 regarding reaction steps, yields, and precursor availability. The prepared conjugates were investigated regarding cytotoxicity using SRB assays and a set of human tumor cell lines. The highest cytotoxicity was observed for piperazinyl spacered compound 22. Thereby, EC50 values of 1.5 μM (for A375 melanoma) and 1.7 μM (for A2780 ovarian carcinoma) were determined. Conjugates 22 and 24 were selected for further cytotoxicity investigations including fluorescence microscopy, annexin V assays and cell cycle analysis.
- Kahnt, Michael,Hoenke, Sophie,Fischer, Lucie,Al-Harrasi, Ahmed,Csuk, René
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- CYANOTRIAZOLE COMPOUNDS AND USES THEREOF
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The present invention provides a compound of Formula (I), or a pharmaceutically acceptable salt thereof: (I) wherein R1, R2, R3, and R4 are as defined herein. The present invention further provides therapeutic uses of these compounds, for example against human African typanosomiasis; pharmaceutical compositions comprising these compounds, and compositions comprising these compounds with a therapeutic co-agent.
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Paragraph 00177
(2020/01/11)
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- PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY
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This application pertains to orthogonally protected esters of peptide nucleic acid (PNA) monomers, which ester groups can be removed under conditions that permit typical backbone and side chain acid- and base-labile protecting groups to remain substantially intact thereby permitting the high yield of PNA monomer carboxylic acids that are suitable for use in PNA oligomer synthesis. Exemplary ester groups include, but are not limited to, 2,2,2-trichloroethyl (TCE), 2,2,2-tribromoethyl (TBE), 2-bromoethyl (2-BE) and 2-iodoethyl groups (2-IE). This invention also pertains to novel methods for the synthesis of Backbone Ester compounds and related Backbone Ester Acid Salts.
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Paragraph 00360
(2018/10/19)
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- In situ generation of nitrile oxides from copper carbene and tert -butyl nitrite: Synthesis of fully substituted isoxazoles
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Herein, we present a novel [3 + 2] cycloaddition reaction of β-keto esters with nitrile oxides, which were generated in situ from copper carbene and tert-butyl nitrite. This three-component reaction provides new methodology for the direct synthesis of fully substituted isoxazole derivatives, featuring mild reaction conditions, readily accessible starting materials and simple operation. The experimental studies and DFT calculations suggest that the reaction starts with the generation of the key intermediate nitrile oxides, followed by a [3 + 2] cycloaddition reaction of β-keto esters to give the final isoxazole products.
- Chen, Rongxiang,Ogunlana, Abosede Adejoke,Fang, Shangwen,Long, Wenhao,Sun, Hongmei,Bao, Xiaoguang,Wan, Xiaobing
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supporting information
p. 4683 - 4687
(2018/07/06)
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- Regio- and Stereoselective Copper(II)-Catalyzed Hydrosilylation of Activated Allenes in Water: Access to Vinylsilanes
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By using catalytic amounts of copper(II), 4-picoline, and dimethylphenylsilylpinacol borane, a series of allenoates were silylated on the β carbon in good to excellent yields and high (E)-selectivity. The mild and efficient silylation method is conducted in water under atmospheric conditions to afford vinylsilanes.
- Pashikanti, Srinath,Calderone, Joseph A.,Nguyen, Matthew K.,Sibley, Christopher D.,Santos, Webster L.
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supporting information
p. 2443 - 2446
(2016/06/09)
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- Synthesis of 1,4-enamino ketones by [3,3]-rearrangements of dialkenylhydroxylamines
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The synthesis of 1,4-enamino ketones has been achieved through the [3,3]-rearrangement of dialkenylhydroxylamines generated from the addition of N-alkenylnitrones to electron-deficient allenes. The mild conditions required for this reaction, and the simultaneous installation of a fluorenyl imine N-protecting group as a consequence of the rearrangement, avoid spontaneous cyclization of the 1,4-enamino ketones to form the corresponding pyrroles and allow for the isolation and controlled divergent functionalization of these reactive intermediates. The optimization, scope, and tolerance of the new method are discussed with demonstrations of the utility of the products for the synthesis of pyrroles, 1,4-diones, and furans.
- Pecak, Wiktoria H.,Son, Jongwoo,Burnstine, Amy J.,Anderson, Laura L.
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supporting information
p. 3440 - 3443
(2014/07/21)
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- Intramolecular cyclopropanation of bromodiazoacetates
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A series of allylic diazoacetates were prepared from the corresponding allylic alcohols and bromoacetyl bromide. When the allylic diazoacetates were treated with 1,8-diazabicyclo[5.4.0]undec-7-ene and N-bromosuccinimide, a rapid full conversion to the corresponding allylic bromodiazoacetates occurred. Exposure of the allylic bromodiazoacetates to rhodium(II) catalysts induced an intramolecular cyclopropanation and gave cyclopropyl bromolactones in yields that were low to good, depending on the substitution pattern. Georg Thieme Verlag Stuttgart New York.
- Bolsones, Marianne,Bonge-Hansen, Hanne Therese,Bonge-Hansen, Tore
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supporting information
p. 221 - 224
(2014/02/14)
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- Solvent-Controlled Bifurcated Cascade Process for the Selective Preparation of Dihydrocarbazoles or Dihydropyridoindoles
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A solvent-controlled cascade process has been identified for the dual purpose of the preparation of either dihydrocarbazoles or dihydropyridoindoles from identical N-aryl-α,β-unsaturated nitrones and electron-deficient allene starting materials. These reactions proceed smoothly under mild metal-free conditions affording a range of two types of skeletally distinct indole-based heterocycles in high yield and diastereoselectivity. These transformations demonstrate the use of a bifurcated cascade process that hinges on the ring-opening event of a benzazepine intermediate for the synthesis of skeletally diverse heterocyclic products and rapid access to biologically-significant, indole-based structures.
- Mo, Dong-Liang,Wink, Donald J.,Anderson, Laura L.
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supporting information
p. 13217 - 13225
(2016/02/19)
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- NOVEL CONJUGATES, PREPARATION THEREOF, AND THERAPEUTIC USE THEREOF
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Provided herein are cryptophycin conjugates and compositions containing them. Methods of making and using such compounds also are provided
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- A near-infrared fluorescent calcium probe: A new tool for intracellular multicolour Ca2+ imaging
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We report a novel near-infrared fluorescent calcium probe (KFCA), which has good optical properties such as intense NIR fluorescence emission (670 nm, QY: 0.24), excellent ON/OFF ratio (120-fold), and good wavelength-compatibility with visible-light-emissive fluorophores (Fluo-4, DsRed2), and which is applicable for real-time dual-colour intracellular Ca2+ imaging.
- Matsui, Akihiro,Umezawa, Keitaro,Shindo, Yutaka,Fujii, Tomohiko,Citterio, Daniel,Oka, Kotaro,Suzuki, Koji
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supporting information; scheme or table
p. 10407 - 10409
(2011/11/06)
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- Total synthesis of peloruside a through kinetic lactonization and relay ring-closing metathesis cyclization reactions
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The other side: A convergent total synthesis of peloruside A (1) is described. The key strategic features are a diastereoselective lactonization to generate a C5-C9 valerolactone from the C2-symmetric ketone 3, and a relay ring-closing metathesis reaction to produce a dehydrovalerolactone 2. A new isomer of 1, the valerolactone isopeloruside A (iso-1), was identified. MOM=methoxymethyl.
- Hoye, Thomas R.,Jeon, Junha,Kopel, Lucas C.,Ryba, Troy D.,Tennakoon, Manomi A.,Wang, Yini
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supporting information; experimental part
p. 6151 - 6155
(2010/11/18)
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- Cross-dehydrogenative coupling reactions by transition-metal and aminocatalysis for the synthesis of amino acid derivatives
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The direct approach: The title coupling reactions of N-aryl glycine esters with unmodified ketones occurred smoothly in the presence of tert-butyl hydroperoxide (TBHP) or 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) under mild conditions (see scheme). The oxidant used for C-H activation determined the selectivity of the reactions for a particular type of ketone substrate. Copyright
- Xie, Jin,Huang, Zhi-Zhen
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supporting information; experimental part
p. 10181 - 10185
(2011/02/27)
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- Synthesis of 1,4,5,6-tetrachloro-7,7-dimethoxybicyclo[2.2.1]hept-5- enylmethyl haloacetates
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The possibility of preparing 1,4,5,6-tetrachloro-7,7-dimethoxybicyclo[2.2. 1]hept-5-enylmethyl haloacetates by the reaction of tetrachlorodimethoxycyclopentadiene with allyl haloacetates was examined. The effect of various factors on the product yield was studied, and the optimal synthesis conditions were found.
- Kyazymova,Mamedbeili,Abdiev,Nagiev,Alieva,Nagiev
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experimental part
p. 102 - 106
(2009/09/06)
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- Synthesis of bicyclo[2.2.1]hept-5-enyl methyl esters of haloacetic acids
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Synthesis of norbornenyl methyl esters of a number of haloacetic acids via [4+2] cycloaddition of cyclopentadiene to allyl esters of these acids was examined. The yield and isomer composition of the synthesized compounds were examined in relation to the reaction conditions, and the best conditions for their preparation were found.
- Kyazimova,Mamedbeili,Nagiev,Suleimanova,Khalilov
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experimental part
p. 1803 - 1807
(2009/09/08)
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- Hydrazone- and hydrazide-containing N-substituted glycines as peptoid surrogates for expedited library synthesis: Application to the preparation of Tsg101-directed HIV-1 budding antagonists
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(Chemical Equation Presented) Replacing the Pro6 in the p6 Gag-derived 9-mer "P-E-P-T-A-P-P-E-E" with N-substituted glycine (NSG) residues is problematic. However, incorporation of hydrazone amides ("peptoid hydrazones") can be readily achieved in library fashion. Furthermore, reduction of these hydrazones to N-substituted "peptoid hydrazides" affords a facile route to library diversification. This approach is demonstrated by application to Tsg101-binding compounds designed as potential HIV budding antagonists.
- Liu, Fa,Stephen, Andrew G.,Adamson, Catherine S.,Gousset, Karine,Aman, M. Javad,Freed, Eric O.,Fisher, Robert J.,Burke Jr., Terrence R.
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p. 5165 - 5168
(2007/10/03)
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- The effect of receptor clustering on vesicle-vesicle adhesion
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As part of our studies into how the localization of cell adhesion molecules into lipid rafts may affect cell adhesion, we developed Cu(1), a synthetic copper(iminodiacetate)-capped receptor able to phase separate from fluid phospholipid bilayers. The extent to which Cu(1) clustered into adhesive patches on the surface of vesicles could be controlled by changing vesicle composition. Extensive receptor phase separation significantly enhanced vesicle-vesicle adhesion; only vesicles with adhesive patches (blue fluorescence) adhered to their conjugate histidine-coated vesicles (red fluorescence) to form large vesicle aggregates (shown). Copyright
- Mart, Robert J.,Liem, Kwan Ping,Wang, Xi,Webb, Simon J.
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p. 14462 - 14463
(2008/02/02)
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- 2,3-Dihydro-4H-1,3-oxazin-4-ones, novel auxiliaries for the stereoselective synthesis of 1β-methylcarbapenems
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Dihydrooxazinones 9, prepared from benzylcyanide in two steps serve as efficient auxiliaries for the stereoselective synthesis of β-methylcarbapenem intermediate 2. Reformatsky-type reactions of 4-acetoxyazetidinone with α-bromopropionyl dihydrooxazinone 10 provided β-methylazetidinones 4 in high diastereoselectivities. The auxiliaries 9 were also easily removed in the Dieckmann cyclization leading to β-methylcarbapenem skeletons. Practical synthesis of β-methylenolphosphates 2 from 4-acetoxyazetidinone 3 was achieved in three steps (61-77% overall yield).
- Pyun,Jeong,Jung,Kim,Lee,Lee,Kim
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p. 1950 - 1952
(2007/10/03)
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- Transition-metal-catalyzed carbenoid reactions of sulfonium ylides
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Olefins undergo cyclopropanation with diphenylsulfonium (ethoxycarbonyl)methylide (=diphenyl-sulfonium 2-ethoxy-2-oxoethylide; 3a) in the presence of chiral Cu(I) or Rh(II) catalysis, trans/cis Ratios and ee's of the cyclopropanes 6 obtained with this ylide in the presence of a chiral Cu(I) catalyst 7 are identical with those obtained with ethyl diazoacetate (4). In the case of catalysis with Rh(II), the trans/cis ratios of the cyclopropanes as well as the enantioselectivity change slightly upon going from the ylide 3a to diazoacetate 4.
- Mueller, Paul,Fernandez, Daniel,Nury, Patrice,Rossier, Jean-Claude
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p. 935 - 945
(2007/10/03)
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- Cyclization of allyl α-halocarboxylates in the presence of metallocomplex initiators
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Allyl trichloroacetate and allyl 2,2-dichloropropionate, unlike allyl bromoacetate and allyl 2-bromopropionate, undergo cyclization into γ-lactones in the presence of a Fe(CO)5-amide system. All these esters undergo reductive dehalogenation under the action of the Bun3SnH-AlBN system.
- Terent'ev,Vasil'eva,Kuz'mina,Mysov,Belokon
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p. 764 - 766
(2007/10/03)
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- A versatile building block for the synthesis of substituted cyclopropanephosphonic acid esters
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By the effect of iodine, solid K2CO3 and a lipophilic quaternary ammonium salt phosphonoacetic acid allylic esters 4 were converted to cyclopropanephosphonic acid derivatives anellated to a five membered lactone ring 6 serving as good starting material for biologically active products. The reaction of cyclopropanation has been assumed to proceed by SET induced radical type elemental steps. Direct evidences were given by ESR for the 6-endo regioselectivity in the closure of electrophilic radical 11. An interesting and new exchange reaction of phosphonic ester moiety by iodine is also observed.
- Toeke, Laszlo,Jaszay, Zsuzsa M.,Petnehazy, Imre,Clementis, Gyoergy,Vereczkey, Gyoergyi D.,Koevesdi, Istvan,Rockenbauer, Antal,Kovats, Katalin
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p. 9167 - 9178
(2007/10/02)
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- Phenoxyphenyl phosphinates
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Novel phenoxy-, phenylthio, anilino-, benzyl-, pyridyloxy-, pyridylthio-, pyridylamino-, or pyridylmethyl-phenyl substituted phosphinates and phosphinothioates, synthesis thereof, intermediates therefore, and the use of said novel compounds for the control of weeds.
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- HOMOLYTIC DISPLACEMENT AT CARBON. XI. INTRAMOLECULAR HOMOLYTIC DISPLACEMENT AS A ROUTE TO CYCLOPENTANE AND TETRAHYDROFURAN DERIVATIVES FROM HEX-5-ENYL- AND HEX-3-OXO-5-ENYLCOBALOXIMES
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5-Methylhex-5-enylcobaloxime reacts with carbon tetrachloride and with fluorotrichloromethane at 80-100 deg C to give substantially pure 1-methyl-1-(Β,Β,Β-trichloroethyl)- and 1-methyl-1-(β-fluoro-β,β-dichloroethyl)-cyclopentane.Hex-5-enylcobaloxime also gives trichloroethylcyclopentane from carbon tetrachloride, but the yield is dependent on the concentration of carbon tetrachloride.Similar cyclisation to give trichloroethyl- or fluorodichloroethyltetrahydrofuran is observed in the reactions of hex-3-oxo-5-enylcobaloxime with carbon tetrachloride and fluorotrichloromethane.However, no cyclisation was observed in the reactions of the ester, hex-2-one-3-oxo-5-enylcobaloxime, with carbon tetrachloride.These reactions are believed to take place by attack of a polyhalogenomethyl radical at the terminal unsaturated carbon of the organic ligand, followed either by an intramolecular homolytic displacement in which the carbon radical at position-5 attacks carbon-1 with displacement of cobaloxime(II), or by a halogen atom abstraction.
- Bongars, Christophe,Bougeard, Peter,Bury, Adrian,Cooksey, Christopher J.,Johnson, Michael D.,et al.
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p. 163 - 172
(2007/10/02)
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