17336-78-6Relevant articles and documents
Prevention of mitochondrial membrane permeabilization and pancreatic β-cell death by an enantioenriched, macrocyclic small molecule
Jimmidi, Ravikumar,Shroff, Govardhan K.,Satyanarayana,Reddy, B. Ramesh,Kapireddy, Jahnavi,Sawant, Mithila A.,Sitaswad, Sandhya L.,Arya, Prabhat,Mitra, Prasenjit
supporting information, p. 1151 - 1156 (2014/03/21)
Mitochondria produce the majority of cellular energy through the process of oxidative phosphorylation and play a central role in regulating the functionality and survival of eukaryotic cells. Under physiological stress, mitochondrial membrane permeabilization results in the release of apoptogenic material such as cytochrome c in the cytoplasm, which thereby initiates caspase activation and the consequent cell death. In our present study, we screened a series of compounds for their ability to inhibit mitochondrial membrane permeabilization and to prevent cytochrome c release during the endoplasmic reticulum stress in cultured pancreatic β-cells. Three benzofuran-based macrocyclic small molecules, that is, 2.4c, c104, and c108, were found to restore the depolarization of mitochondrial membrane potential and to prevent the release of cytochrome c from mitochondria. Interestingly, the acyclic precursor of 2.4c (i.e., 2.3c) did not show any effect, whereas the macrocyclic derivative obtained by utilizing ring-closing metathesis as the "stitching technology" led to this function. The macrocyclic architecture seems to play a crucial role in presenting various functional moieties in the right orientation to observe this effect. A series of compounds for their ability to inhibit mitochondrial membrane permeabilization and to prevent cytochrome c release during endoplasmic reticulum stress in cultured pancreatic β-cells is screened. Three benzofuran-based macrocyclic small molecules were found to restore the depolarization of the mitochondrial membrane potential and to prevent the release of cytochrome c from mitochondria. MPTP = Mitochondrial Permeability Transition Pore. Copyright
Synthesis of a structural analogues of the cinchona alkaloids
Furukawa, Kadzushi,Katsukawa, Masahiro,Nuruzzaman, Mohammad,Kobayashi, Yuichi
, p. 159 - 166 (2008/09/17)
Five olefins, each possessing an aryl (Ar) group, an aliphatic moiety, and a protected amino group as N-Teoc (-CO2(CH2)TMS) or N3 at the aliphatic end, were converted to the corresponding epoxides with high ee. The amino g
Oxidative fragmentations of 2-(trimethylsilyl)ethyl sulfoxides - Routes to alkane-, arene-, and highly substituted 1-alkenesulfinyl chlorides
Schwan, Adrian L.,Strickler, Rick R.,Dunn-Dufault, Robert,Brillon, Denis
, p. 1643 - 1654 (2007/10/03)
The preparation of a collection of alkyl, aryl, and 1-alkenyl 2-(trimethylsilyl)ethyl sulfoxides is outlined, using mostly vinyltrimethylsilane or 2-(trimethylsilyl)ethanesulfenyl chloride (5) as key starting materials. The 2-(trimethylsilyl)ethyl group can be cleaved from many of the sulfoxides under oxidative fragmentation conditions using sulfuryl chloride and the reaction represents a new protocol for sulfinyl chloride synthesis. The method is suitable for most alkane- and arenesulfinyl chlorides (3), but is limited to highly substituted vinylic sulfinyl chlorides. 1-Alkenyl 2-(trimethylsilyl)ethyl sulfoxides with reduced double bond substitution (6, 7, 11) succumb to reactions involving chlorination of the double bond. The β-effect of silicon is invoked to explain the ability of the 2-(trimethylsilyl)ethyl group to induce C-S bond scission under the oxidative cleavage reaction conditions. A mechanism is offered to account for the role played by the β-silicon atom of the 2-(trimethylsilyl)ethyl group. Indeed, the silicon atom is self-sacrificial in that it diverts the course of the reaction from the usual α-carbon chlorination mode to one of oxidative cleavage, whereby the 2-(trimethylsilyl)ethyl group is lost. The overall reaction calls upon the ability of silicon atoms to donate electron density by hyperconjugation.
Exploratory studies of H-atom abstraction and silyl-transfer photoreactions of silylalkyl ketones and (silylalkyl)phthalimides
Lee, Yean Jang,Ling, Rong,Mariano, Patrick S.,Yoon, Ung Chan,Kim, Dong Uk,Oh, Sun Wha
, p. 3304 - 3314 (2007/10/03)
Exploratory studies have been conducted to probe competitive H-atom abstraction and SET-promoted, silyl-transfer reactions of excited states of silylalkyl ketones and (silylalkyl)phthalimides. Photochemical investigations with the (silylalkyl)phthalimides have demonstrated that typical γ-H atom abstraction reactions occur upon irradiation in less polar and less silophilic solvents. In contrast, irradiation of these substances in polar-protic-silophilic solvents results in product formation via pathways involving SET-induced desilylation. Photoreactions of silylamido-aryl ketones in either nonsilophilic or silophilic solvents take place almost exclusively by sequential SET silyl-transfer routes to produce azetidine products. Finally, the chemical selectivities of photochemical reactions of silylpropyl-aryl ketones appear to depend on medium polarity and silophilicity. Irradiation of these substrates in less polar-nonsilophilic solvents leads to almost exclusive formation of acetophenone and vinyltrimethylsilane in essentially equal yields by a reaction pathway initiated by γ-H atom abstraction and 1,4-biradical fragmentation. However, irradiation of these substances in polar-silophilic solvents produces acetophenone and vinyltrimethylsilane in an ca. 1.7:1 ratio reflecting the fact that a silyl-transfer pathway competes with H-atom abstraction under these conditions.
The reaction of 2-trimethylsilylethyl sulfoxides with sulfuryl chloride. A fragmentation route to sulfinyl chlorides
Schwan,Dufault
, p. 3973 - 3974 (2007/10/02)
Sulfinyl chlorides were prepared in good to excellent yields by reacting aryl or alkyl 2-trimethylsilylethyl sulfoxides with SO2Cl2.
Reduction of Halosilanes by Organotin Hydrides
Wilt, James W.,Belmonte, Frank G.,Zieske, Paul A.
, p. 5665 - 5675 (2007/10/02)
A study of the reduction of halosilanes with organotin hydrides is described.The free radical chain mechanism indicated by the results obtained parallels that known for the comparable reduction of haloalkanes, but the reactivity of α-haloalkanes is considerable enhanced.Mechanistic studies suggest that the polar nature of the halogen abstraction step in the radical chain sequence, which places incremental negative charge adjacent to silicon, is the principal reason for this enhanced reactivity.Structure-reactivity studies indicat the gem-dimethylsilyl function to be an electronic transmitter.The ρ values for reduction of aryldimethyl(chloromethyl)silanes and substituted benzyl chlorides by tri-n-butyltin hydride are essentially identical (+0.45).Reduction of (chloromethyl)trimethylsiulane with aryldimethyltin hydrides, conversely, yielded a ρ value of -1.61.The reduction produced racemic product from an optically active α-chlorosilane, the synthesis of which appears to the first reported.Other syntheses of variuos halosilanes of interest are also described.The title reduction is specific for carbon-halogen bonds.Silicon-halogen bonds are not affected, a distinction that should make the reduction synthetically useful.Because the increased reactivity of α-halosilanes in the reduction has thus been ascribed to a kinetic polar effect in a critical step of the mechanism, no compelling argument for special thermodynamic stability in α-silyl radicals themselves can be made.
