40630-84-0Relevant articles and documents
Computational chemical analysis of Ru(II)-Pheox–catalyzed highly enantioselective intramolecular cyclopropanation reactions
Nakagawa, Yoko,Nakayama, Naofumi,Goto, Hitoshi,Fujisawa, Ikuhide,Chanthamath, Soda,Shibatomi, Kazutaka,Iwasa, Seiji
, p. 52 - 61 (2019)
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.
Calix[4]arene-Modified Oligosiloxane as a Quasi-Immobilized Neutral Carrier for Silicone-Rubber-Membrane Sodium Ion-Selective Electrodes
Kimura, Keiichi,Tsujimura, Yutaka,Yokohama, Masaaki,Maeda, Takumi
, p. 657 - 660 (1998)
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.
Macrocyclic FKBP51 Ligands Define a Transient Binding Mode with 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
supporting information, p. 13257 - 13263 (2021/05/07)
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.
Synthesis and cytotoxicity evaluation of DOTA-conjugates of ursolic acid
Kahnt, Michael,Hoenke, Sophie,Fischer, Lucie,Al-Harrasi, Ahmed,Csuk, René
, (2019/06/20)
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.
CYANOTRIAZOLE COMPOUNDS AND USES THEREOF
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Paragraph 00177, (2020/01/11)
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.
PEPTIDE NUCLEIC ACID (PNA) MONOMERS WITH AN ORTHOGONALLY PROTECTED ESTER MOIETY
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Paragraph 00360, (2018/10/19)
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.
In situ generation of nitrile oxides from copper carbene and tert -butyl nitrite: Synthesis of fully substituted isoxazoles
Chen, Rongxiang,Ogunlana, Abosede Adejoke,Fang, Shangwen,Long, Wenhao,Sun, Hongmei,Bao, Xiaoguang,Wan, Xiaobing
supporting information, p. 4683 - 4687 (2018/07/06)
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.
Regio- and Stereoselective Copper(II)-Catalyzed Hydrosilylation of Activated Allenes in Water: Access to Vinylsilanes
Pashikanti, Srinath,Calderone, Joseph A.,Nguyen, Matthew K.,Sibley, Christopher D.,Santos, Webster L.
supporting information, p. 2443 - 2446 (2016/06/09)
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.
Synthesis of 1,4-enamino ketones by [3,3]-rearrangements of dialkenylhydroxylamines
Pecak, Wiktoria H.,Son, Jongwoo,Burnstine, Amy J.,Anderson, Laura L.
supporting information, p. 3440 - 3443 (2014/07/21)
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.
Intramolecular cyclopropanation of bromodiazoacetates
Bolsones, Marianne,Bonge-Hansen, Hanne Therese,Bonge-Hansen, Tore
supporting information, p. 221 - 224 (2014/02/14)
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.
