RESUMO
Out-of-plane distortions of a cofactor molecule in a protein active site are functionally important, and in photoreceptors, it has been proposed that they are crucial for spectral tuning and energy storage in photocycle intermediates. However, these subtle structural features are often beyond the grasp of structural biology. This issue is strikingly exemplified by photoactive yellow protein: its 14 independently determined crystal structures exhibit considerable differences in the dihedral angles defining the chromophore geometry, even though most of these are at excellent resolution. Here we developed a strategy to verify cofactor distortions in crystal structures by using quantum chemical calculations and chiroptical spectroscopy, particularly Raman optical activity and electronic circular dichroism spectroscopies. Based on this approach, we identify seven crystal structures with the chromophore geometries inconsistent with the experimentally observed data. The strategy implemented here promises to be widely applicable to uncovering cofactor distortions at active sites and to studies of reaction intermediates.
Assuntos
Fotorreceptores Microbianos , Análise Espectral Raman , Domínio Catalítico , Análise Espectral Raman/métodos , Proteínas de Bactérias/química , Cristalografia , Espectrofotometria Ultravioleta , Fotorreceptores Microbianos/químicaRESUMO
Various nitrogen nucleophiles were easily added to in situ-generated 1-(trifluoromethyl)-2-(phenylthio)ethyne to afford the corresponding trifluoromethyl enamines in good-to-high yields and with high regio- and stereocontrol under very mild conditions.
RESUMO
The iodine-promoted cyclization of various N-(2-CF3-2-NHTs)ethylbenzimidazoles and N-(2-CF3-2-NHTs)ethylindoles proceeded smoothly and efficiently under mild basic conditions. This reaction did not require transition metals and afforded the corresponding CF3-dihydroimidazobenzimidazoles and CF3-dihydroimidazoindoles in 85-93% and 42-82% yields, respectively.
RESUMO
The fluorinated building block strategy and the direct fluorination strategy are of great importance for the synthesis of new fluorinated molecules. These strategies complement each other and can be combined to develop a new methodology for the construction of a wide variety of fascinating organofluorine compounds. In our opinion, the versatile building blocks used in this method should satisfy the following conditions: 1) readily prepared from commercially available reagents; 2) easy to handle; 3) storage under ordinary conditions without noticeable decomposition; 4) wide applicability. Based on the aforementioned requirements, we focused on the use of vinyl sulfonium salts. This brief review describes the synthesis of five types of fluorinated vinyl sulfonium salts and their reactions. Especially, we featured typical fluorinated groups containing trifluoromethyl (CF3 ), difluoromethyl (CF2 H), monofluoromethyl (CFH2 ), monofluoro (F) or ß-bromotetrafluoroethyl (BrCF2 CF2 ) moieties in combination with vinyl sulfonium salts.
RESUMO
Trihalo-substituted vinylsilane was readily synthesized in 77% yield and in an excellent regio- and stereoselective manner from in situ-generated fluorosilylacetylene, followed by the addition of I2 and NCS. The silane was committed to sequential Sonogashira coupling with various terminal acetylenes under mild conditions, affording desilylated chlorofluoro-enyne adducts in moderate to good yields.
Assuntos
Alcinos , EstereoisomerismoRESUMO
Photoactive yellow protein (PYP), from the phototrophic bacterium Halorhodospira halophila, is a small water-soluble photoreceptor protein and contains p-coumaric acid (pCA) as a chromophore. PYP has been an attractive model for studying the physical chemistry of protein active sites. Here, we explore how Raman optical activity (ROA) can be used to extract quantitative information on distortions of the pCA chromophore at the active site in PYP. We use 13C8-pCA to assign an intense signal at 826 cm-1 in the ROA spectrum of PYP to a hydrogen out-of-plane vibration of the ethylenic moiety of the chromophore. Quantum-chemical calculations based on density functional theory demonstrate that the sign of this ROA band reports the direction of the distortion in the dihedral angle about the ethylenic C=C bond, while its amplitude is proportional to the dihedral angle. These results document the ability of ROA to quantify structural deformations of a cofactor molecule embedded in a protein moiety.
Assuntos
Proteínas de Bactérias/química , Halorhodospira halophila/química , Hidrogênio/química , Modelos Moleculares , Fotorreceptores Microbianos/química , Análise Espectral Raman/métodos , Teoria QuânticaRESUMO
We report the first [3 + 2] cycloaddition of 2-(trifluoromethyl)-N-tosylaziridine to nitriles using TiF4 as an effective Lewis acid under mild reaction conditions. The reaction proceeded smoothly and afforded the corresponding 4-(trifluoromethyl)-1,3-imidazolines in good yields and with excellent regioselectivity.
RESUMO
The α-fluorovinyl diphenyl sulfonium salt 1 is attractive due to its high potential for the synthesis of mono-fluorinated cyclopropanes and aziridines as useful three-membered rings. The synthetically useful salt 1 is readily prepared from α-fluorovinyl phenyl sulfide and diphenyl iodonium salt in one step.
Assuntos
Aziridinas/química , Ciclopropanos/síntese química , Flúor/química , Sulfetos/química , Compostos de Vinila/química , Aziridinas/síntese química , Cristalografia por Raios X , Ciclopropanos/química , Estrutura Molecular , Sulfetos/síntese química , Compostos de Vinila/síntese químicaRESUMO
2-Aryl-3-fluoro-5-silylthiophenes were readily prepared only in two steps from 2-bromo-3,3,3-trifluoropropene in good yields. These transformations include the first successful S(N)2'-type reaction of 2-bromo-3,3,3-trifluoropropene and benzylthiols and [2,3]sigmatropic rearrangement of 2-bromo-3,3-difluoroallyl benzyl sulfide.
Assuntos
Hidrocarbonetos Bromados/química , Hidrocarbonetos Fluorados/síntese química , Silanos/síntese química , Tiofenos/síntese química , Catálise , Hidrocarbonetos Fluorados/química , Estrutura Molecular , Silanos/química , Estereoisomerismo , Compostos de Sulfidrila/química , Sulfetos/química , Tiofenos/químicaRESUMO
2-Trifluoromethyl-N-tosylaziridine reacted with various aldehydes in the presence of a catalytic amount of AgSbF(6) to provide the corresponding cis-4-trifluoromethyl-2-substituted-N-tosyl-1,3-oxazolidines with excellent regio- and stereoselectivity.
RESUMO
The Mizoroki-Heck reaction of (1-fluorovinyl)methyldiphenylsilane with a variety of aryl iodides was accomplished under the conditions composing Pd(OAc)(2), Ag(2)CO(3) and MS 4 Å in 1,4-dioxane to give the corresponding (E)-ß-aryl-(α-fluorovinyl)methyldiphenylsilanes with excellent stereoselectivity.
RESUMO
Fluoro(silyl)acetylenes and fluoro(stannyl)acetylenes underwent a radical addition reaction of THF to furnish the corresponding fluorinated cyclic ethers in moderate to good yields. These intriguing addition reaction proved to proceed via a radical reaction mechanism.
RESUMO
(Beta-trifluoromethyl)vinyl sulfonium salt as a novel three-carbon fluorinated building block was conveniently prepared from easily available (beta-trifluoromethyl)vinyl sulfide and diphenyl iodonium salt in excellent yield. This easily handled crystalline reagent displayed two types of useful transformation involving aziridination and vinylation to afford the corresponding trifluoromethylated compounds in excellent yields.
RESUMO
The reaction of (trifluoromethyl)dimethylphenylsilylacetylene and (eta(2)-propene)Ti(O(i)Pr)(2) generated in situ smoothly proceeded giving the corresponding (eta(2)-1-dimethylphenylsilyl-2-trifluoromethylalkyne)Ti(O(i)Pr)(2), which reacted with aldehydes and ketones to afford the corresponding addition products in good yields with good to excellent regioselectivity.
Assuntos
Compostos Organometálicos/química , Compostos Organometálicos/síntese química , Compostos de Organossilício/síntese química , Titânio/química , Estrutura Molecular , Compostos de Organossilício/química , EstereoisomerismoRESUMO
N-Methylation by sequential treatment of 5-tributylstannyl-4-fluoro-1H-pyrazole 1 with LDA and iodomethane regioselectively afforded the compound 2a in high yield. The addition reaction of 5-lithiated-4-fluoro-1H-pyrazole generated from 2a with a wide range of electrophiles allowed a facile introduction of different substituents at position 5 in good yields. The adduct 3d was efficiently converted to N-methyl-chromeno[2,3-d]pyrazol-9-one 9 in 3 steps.
Assuntos
Pirazóis/síntese química , Espectroscopia de Ressonância Magnética , Pirazóis/químicaRESUMO
The palladium catalyzed cross-coupling reactions of aryl iodides and 5-tributylstannyl-4-fluoropyrazole prepared from fluoro(tributylstannyl)acetylene proceeded smoothly giving the corresponding 5-aryl-4-fluoropyrazole in good yields.
Assuntos
Paládio/química , Pirazóis/química , Acetona/análogos & derivados , Acetona/química , Catálise , Ligação de Hidrogênio , Estrutura MolecularRESUMO
The cesium fluoride (CsF)-assisted cross-coupling reaction of (1-fluorovinyl)methyldiphenylsilane (1) with aryl halides and aryl triflates was examined. The reaction with aryl iodides smoothly proceeded to afford the corresponding (1-fluorovinyl)arenes in the presence of a catalytic amount of CuI and Pd(PPh(3))(4) in aprotic polar solvents such as DMF, DMI, DMA, and NMP in good yields. A variety of functional groups (nitro, ester, ketone, and ether) on the aromatic rings can be tolerated under these mild conditions. Aryl iodides are superior to aryl bromides as the coupling reaction partner. The cross-coupling reaction of 1 with aryl triflates instead of aryl halides was also accomplished in the presence of tetrabutylammonium iodide (n-Bu(4)NI) as the additive under similar conditions.