- Highly Selective Radical Monoreduction of Dihalides Confined to a Dynamic Supramolecular Host
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Reduction of alkyl dihalide guests (2–5 and 7) with trialkylsilanes (R3SiH) was performed in water-soluble host 1 to investigate the effects of confinement on fast radical reactions (k≥103 m?1 s?1). High selectivity (>95 %) for mono-reduced products was observed for primary and secondary dihalide guests under mild conditions. The results highlight the importance of host–guest complexation rates to modulate the product selectivity in radical reactions.
- Petroselli, Manuel,Rebek, Julius,Yu, Yang
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- Inhibition of protein kinase Cα by dequalinium analogues: Dependence on linker length and geometry
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Analogues of a bipartite compound, dequalinium (DECA) (quinolinium, 1,1'-(1,10-decanediyl)bis(4-amino-2-methyl diiodide)), were tested for inhibition of protein kinase Cα (PKCα). In vitro assays of monomeric and dimeric analogues support a model in which DECA inhibits PKCα by an obligatory two-point contact, a unique mechanism among PKC inhibitors. The presence of unsaturation in the center of the C10-alkyl linker produced geometric isomers with different inhibitory potencies: cis IC50 = 52 ± 12 μM and trans IC50 = 12 ± 3 μM, where the trans isomer was equipotent to that of the saturated C10-DECA. DECA analogues with longer, saturated linkers (C12, C14, or C16) exhibited enhanced inhibitory potencies which reached a plateau with the C14-linker (IC50 = 2.6 ± 0.2 μM). Metastatic melanoma cells treated with 250 nM C12-, C14-, or C16-DECA and irradiated with long-wave UV light (which causes irreversible inhibition of PKCα by DECA) confirmed the linker-dependent inhibition of intracellular PKCα activity.
- Qin, Donghui,Sullivan, Regina,Berkowitz, William F.,Bittman, Robert,Rotenberg, Susan A.
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- A Simple Convenient Procedure for Iodination of Alcohols and Reductive Iodination of Carbonyl Compounds using N,N-Diethylaniline-Borane-I2 system.
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Alcohols, carboxylic acids and carbonyl compounds give the corresponding alkyl iodides in moderate to good yields on reaction with N,N-diethylaniline-borane complex and iodine.
- Reddy, Ch. Kishan,Periasamy, M.
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- Low-Frequency Raman Spectra of Even α,ο-Disubstituted n-Alkanes
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Low-frequency Raman spectra of even α,ο-disubstituted n-alkanes have been recorded.The major features in the spectra arise from whole-chain longitudinal and bending vibrations.The effects of end group, chain lenght, and temperature on the frequencies of these vibrations are described, and the frequencies of the longitudinal vibrations are interpreted in terms of the chain model of Minoni and Zerbi.
- Viras, Kyriakos,Viras, Fontini,Campbell, Carl,King, Terence A.,Booth, Colin
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- Probing the Existence of a Metastable Binding Site at the β2-Adrenergic Receptor with Homobivalent Bitopic Ligands
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Herein, we report the development of bitopic ligands aimed at targeting the orthosteric binding site (OBS) and a metastable binding site (MBS) within the same receptor unit. Previous molecular dynamics studies on ligand binding to the β2-adrenergic receptor (β2AR) suggested that ligands pause at transient, less-conserved MBSs. We envisioned that MBSs can be regarded as allosteric binding sites and targeted by homobivalent bitopic ligands linking two identical pharmacophores. Such ligands were designed based on docking of the antagonist (S)-alprenolol into the OBS and an MBS and synthesized. Pharmacological characterization revealed ligands with similar potency and affinity, slightly increased β2/β1AR-selectivity, and/or substantially slower β2AR off-rates compared to (S)-alprenolol. Truncated bitopic ligands suggested the major contribution of the metastable pharmacophore to be a hydrophobic interaction with the β2AR, while the linkers alone decreased the potency of the orthosteric fragment. Altogether, the study underlines the potential of targeting MBSs for improving the pharmacological profiles of ligands.
- Gaiser, Birgit I.,Danielsen, Mia,Marcher-R?rsted, Emil,R?pke J?rgensen, Kira,Wróbel, Tomasz M.,Frykman, Mikael,Johansson, Henrik,Br?uner-Osborne, Hans,Gloriam, David E.,Mathiesen, Jesper Mosolff,Sejer Pedersen, Daniel
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p. 7806 - 7839
(2019/09/07)
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- BIVALENT BROMODOMAIN LIGANDS, AND METHODS OF USING SAME
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Described herein are compounds capable of modulating one or more biomolecules substantially simultaneously, e.g., modulating two or more binding domains (e.g., bromodomains) on a protein or on different proteins. For example, in one aspect, a bivalent compound or a pharmaceutically acceptable salt, stereoisomer, metabolite, or hydrate thereof is provided. In another aspect, a method of treating a disease associated with a protein having tandem bromodomains in a patient in need thereof is provided. The method comprises administering to the patient the bivalent compound as described.
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Paragraph 00382; 00383
(2015/06/11)
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- New synthesis of (11Z,13Z)-11,13-Hexadecadienal, the female sex pheromone of the navel orangeworm
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(11Z,13Z)-11,13-Hexadecadienal, the female sex pheromone of the navel orangeworm (Amyelois transitella), was synthesized from commercially available 10-bromo-1-decanol in a 27% overall yield (8 steps). The synthesis was achieved by using 10-iododecanal, trimethylsilylacetylene and (Z)-1-bromo-12-butene as the key building blocks, employing Sonogashira-Hagihara coupling and Brown's hydroboration-protonolysis as the key reactions. The terminal formyl group was installed in the earlier stage of the synthesis rather than in the final step. This procedure enabled the multi-gram-scale preparation of this economically important pheromone.
- Mori, Kenji
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experimental part
p. 2727 - 2730
(2010/09/11)
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- The synthesis of phosphates of long-chain ω-hydroxyalkyl esters of 11-deoxyprostaglandin E1
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Di(p-methylbenzyl) phosphates of ω-hydroxyalkyl esters of 11-deoxyprostaglandin E1 were synthesized from disubstituted 1,10-decane and 1,22-docosane derivatives for studying the permeability of bilayer membranes.
- Sokolov,Turovskii,Lukevits
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- Sharpless AD strategy towards the γ-methyl butenolide unit of acetogenins: Enantioselective synthesis of butenolide I and II with mosquito larvicidal activity
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A novel synthetic strategy toward the γ-methyl butenolides has been established based on Sharpless asymmetric dihydroxylation in high yields and good enantiopurity. The route could be expanded to the synthesis of α,γ-disubstituted butenolide units of naturally occurring annonaceous acetogenins. Utilizing this strategy, three simple natural products with butenolide segments were synthesized enantioselectively.
- He, Yan-Tao,Yang, Hui-Na,Yao, Zhu-Jun
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p. 8805 - 8810
(2007/10/03)
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- Quantum interference effects in self-assembled asymmetric disulfide monolayers: Comparisons between experiment and ab initio/Monte Carlo theories
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Electron transfer measurements between solution redox probes and a Au electrode coated with self-assembled monolayers of symmetric and asymmetric ??-hydroxyalkane disulfides are used to probe the quantum interference between hydrocarbon chains of different lengths. While ab initio theory predicts a measurable destructive interference effect between hydrocarbon chains differing in length by a single methylene unit, electron transfer rates for the ferricyanide and horse heart cytochrome c are more consistent with rates estimated in the absence of the interference effect. The discrepancy between theory and experiment is discussed in light of possible interchain electronic coupling and phase segregation within the monolayers and limitations of the theoretical models.
- Cheng, Jun,Miller, Cary J.
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p. 1058 - 1062
(2007/10/03)
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- Ligh Induced Electron Transfer and Charge Separation of Porphyrin Compounds for Photoelectric Conversion
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A series of artificial photosynthesis prophyrin compounds consisting of electron donor and electron acceptor (compounds 1-6) were synthesized.Their spectroscopic behaviors in solution were investigated and the synthetic molecular devices were prepared with these molecules by using LB technique.It was indicated that multistep electron transfer and charge separation for these compounds actually occur, which is of great advantage to their photoelectric conversion.An efficient energy transfer process takes place for compound 6.A mechanism involving photoinduced electron transfer and multistep charge separation for these compounds was suggested.With only one monolayer of tetrad 1 LB film on the surface of SnO2 conductive glass, high photo-driven voltage and current were obtained. Key words: Intramolecular electron transfer; Photoelectric conversion.
- Cao, Yi,Zhang, Bao-Wen,Qian, Wen-Yuan,Bai, Jian-Wei,Xiao, Xu-Rui,Jia, Jian-Guang
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p. 641 - 650
(2007/10/02)
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- Hydroborations, reductions and reductive iodinations using BHI2:N(C2H5)2Ph complex
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The BHI2:N(C2H5)2Ph complex, prepared by the reaction of BH3:N(C2H5)2Ph with I2, is useful for hydroboration of alkenes, reduction of amides, iodination of alcohols, reductive iodination of carboxylic acids, aldehydes and ketones. Selective hydroboration of monosubstituted olefin over disubstituted olefinic moiety and terminal olefin over internal alkyne moiety have been achieved using this reagent. Carboxylic esters and nitriles are not affected by this reagent. Selective hydroboration of 1-alkenes and selective reductive iodination of cyclohexanone are achieved in the presence of ester and nitrile functional groups.
- Kishan Reddy,Periasamy
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p. 8329 - 8336
(2007/10/02)
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- Synthesis of a new family of water-soluble tertiary phosphine ligands and of their rhodium(I) complexes; olefin hydrogenation in aqueous and biphasic media
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The series of phosphonium phosphines (Ph2P(CH2)nPMe3>X (n = 2, 3, 6, 10; N = NO3-, Cl-, PF6-), henceforth II-, III-, VI- and X-phosphos respectively, have been prepared and characterized.The ligands react with 2 (NBD = norbornadiene) to form the complexes X, one of which, PF6, has been characterized crystallographically.The 1:1 complexes X react with a second equivalent of ligand to form the complexes X, which form very active olefin hydrogenation catalysts in aqueous and aqueous-organic biphasic systems.The effect of chain length on activity is very significant, the complex of VI-phosphos forming the most active catalyst.
- Renaud, Eric,Russell, Robert B.,Fortier, Suzanne,Brown, Stephen J.,Baird, Michael C.
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p. 403 - 415
(2007/10/02)
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- Synthesis and Hypolipidemic and Antidiabetogenic Activities of β,β,β',β'-Tetrasubstituted, Long-Chain Dioic Acids
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β,β,β',β'-Tetrasubstituted, long-chain dioic acids of the general formula HOOC-C(XY)-C(R2)-Q-C(XY)-COOH have been synthesized and evaluated as hypotriglyceridemic-hypocholesterolemic agents in rats and as antidiabetogenic agents in ob/ob diabetic mice.The free carboxyl function of analogues of the series was mandatory for their hypolipidemic-antidiabetogenic effect while nonhydrolyzable diesters were inactive.Other structure-activity relationships were determined as a function of the overall chain length (C12-C22), α,α'-substitutions (X,Y=H,F,Cl,Br,OH,CN), β,β'-substitutions (R=CH3,C6H5), and core substitutions 2, 1,4-C6H42, 1,4-C6H4(CH=CHCH2)2, CH2(OCH2CH2)3OCH2)>.The most effective hypolipidemic-antidiabetogenic members of the series were α,α'-nonsubstituted, β,β'-methyl-substituted analogues of 14-18-carbon chains having either a saturated aliphatic core or a 1,4-bis(propenyl)benzene core in the cis/trans configuration.The hypotriglyceridemic rather than the hypocholesterolemic capacity of members of the series was found to correlate with their respective capacities as liver peroxisomal proliferation in rats.
- Bar-Tana, Jacob,Ben-Shoshan, Shoshana,Blum, Jochanan,Migron, Yoelit,Hertz, Rachel,et al.
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p. 2072 - 2084
(2007/10/02)
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