- Selective Benzylic CH-Borylations by Tandem Cobalt Catalysis
-
Metal-catalyzed C?H activations are environmentally and economically attractive synthetic strategies for the construction of functional molecules as they obviate the need for pre-functionalized substrates and minimize waste generation. Great challenges reside in the control of selectivities, the utilization of unbiased hydrocarbons, and the operation of atom-economical dehydrocoupling mechanisms. An especially mild borylation of benzylic CH bonds was developed with the ligand-free pre-catalyst Co[N(SiMe3)2]2 and the bench-stable and inexpensive borylation reagent B2pin2 that produces H2 as the only by-product. A full set of kinetic, spectroscopic, and preparative mechanistic studies are indicative of a tandem catalysis mechanism of CH-borylation and dehydrocoupling via molecular CoI catalysts.
- Bauer, Matthias,Ghosh, Pradip,Jacobi von Wangelin, Axel,Schoch, Roland
-
supporting information
(2021/11/27)
-
- Tau-Centric Multitarget Approach for Alzheimer's Disease: Development of First-in-Class Dual Glycogen Synthase Kinase 3β and Tau-Aggregation Inhibitors
-
Several findings propose the altered tau protein network as an important target for Alzheimer's disease (AD). Particularly, two points of pharmacological intervention can be envisaged: inhibition of phosphorylating tau kinase GSK-3β and tau aggregation process. On the basis of this consideration and on our interest in multitarget paradigms in AD, we report on the discovery of 2,4-thiazolidinedione derivatives endowed with such a profile. 28 and 30 displayed micromolar IC50 values toward GSK-3β, together with the capacity of inhibiting AcPHF6 aggregation of 60% and 80% at 10 μM, respectively. In addition, they showed PAMPA-BBB permeability, together with a suitable cellular safety profile. 30 also displayed inhibition of both K18 and full-length tau aggregations. Finally, both compounds were able to improve cell viability in an okadaic acid-induced neurodegeneration cell model. To the best of our knowledge, 28 and 30 are the first balanced, nontoxic, dual-acting compounds hitting tau cascade at two different hubs.
- Gandini, Annachiara,Bartolini, Manuela,Tedesco, Daniele,Martinez-Gonzalez, Loreto,Roca, Carlos,Campillo, Nuria E.,Zaldivar-Diez, Josefa,Perez, Concepción,Zuccheri, Giampaolo,Miti, Andrea,Feoli, Alessandra,Castellano, Sabrina,Petralla, Sabrina,Monti, Barbara,Rossi, Martina,Moda, Fabio,Legname, Giuseppe,Martinez, Ana,Bolognesi, Maria Laura
-
supporting information
p. 7640 - 7656
(2018/09/06)
-
- Reduction of N,N-Dimethylcarboxamides to Aldehydes by Sodium Hydride–Iodide Composite
-
A new and concise protocol for selective reduction of N,N-dimethylamides into aldehydes was established using sodium hydride (NaH) in the presence of sodium iodide (NaI) under mild reaction conditions. The present protocol with the NaH-NaI composite allows for reduction of not only aromatic and heteroaromatic but also aliphatic N,N-dimethylamides with wide substituent compatibility. Retention of α-chirality in the reduction of α-enantioriched amides was accomplished. Use of sodium deuteride (NaD) offers a new step-economical alternative to prepare deuterated aldehydes with high deuterium incorporation rate. The NaH-NaI composite exhibits unique chemoselectivity for reduction of N,N-dimethylamides over ketones.
- Chan, Guo Hao,Ong, Derek Yiren,Yen, Zhihao,Chiba, Shunsuke
-
-
- Laying the way to meta-functionalization of naphthalene proton sponge via the use of Schlosser's superbase
-
Lithiation of 1,8-bis(dimethylamino)naphthalene (DMAN) with Schlosser's superbase (n-BuLi–t-BuOK) in the presence of TMEDA in hexane was examined. It has been shown that, compared with previously studied n-BuLi–TMEDA or t-BuLi–TMEDA mixtures, this reagent provides much more selective meta-lithiation. A variety of 3-substituted and 3,6-disubstituted derivatives of DMAN has been prepared in a good to reasonable yield after quenching the reaction mass with different electrophiles. A possibility of further functionalization of thus introduced meta-substituents to synthesize more complex 3-substituted derivatives of DMAN is also demonstrated.
- Antonov, Alexander S.,Bardakov, Victor G.,Pozharskii, Alexander F.,Vovk, Mikhail A.,Misharev, Alexander D.
-
-
- Copper-Catalyzed Aerobic Oxidative Amidation of Benzyl Alcohols
-
A Cu-catalyzed synthesis of amides from alcohols and secondary amines using the oxygen in air as the terminal oxidant has been developed. The methodology is operationally simple requiring no high pressure equipment or handling of pure oxygen. The commercially available, nonprecious metal catalyst, Cu(phen)Cl2, in conjunction with di-tert-butyl hydrazine dicarboxylate and an inorganic base provides a variety of benzamides in moderate to excellent yields. The pKa of amine conjugate acid and electronics of alcohol were shown to impact the selection of base for optimal reactivity. A mechanism consistent with the observed reactivity trends, KIE, and Hammett study is proposed.
- Krabbe, Scott W.,Chan, Vincent S.,Franczyk, Thaddeus S.,Shekhar, Shashank,Napolitano, José G.,Presto, Carmina A.,Simanis, Justin A.
-
p. 10688 - 10697
(2016/11/29)
-
- Cobalt-Catalyzed Benzylic Borylation: Enabling Polyborylation and Functionalization of Remote, Unactivated C(sp3)-H Bonds
-
Cobalt dialkyl and bis(carboxylate) complexes bearing α-diimine ligands have been synthesized and demonstrated as active for the C(sp3)-H borylation of a range of substituted alkyl arenes using B2Pin2 (Pin = pinacolate) as the boron source. At longer reaction times, rare examples of polyborylation were observed, and in the case of toluene, all three benzylic C-H positions were functionalized. Coupling benzylic C-H activation with alkyl isomerization enabled a base-metal-catalyzed method for the borylation of remote, unactivated C(sp3)-H bonds.
- Palmer, W. Neil,Obligacion, Jennifer V.,Pappas, Iraklis,Chirik, Paul J.
-
supporting information
p. 766 - 769
(2016/02/05)
-
- Structurally Simple Benzylidene-Type Photolabile Diol Protecting Groups
-
Two structurally simple photolabile protecting groups for releasing 1,2- and 1,3-diols have been developed. The diols can be protected in high yields and released from their corresponding acetals with high chemical efficiency.
- Ding, Xiong,Devalankar, Dattatray A.,Wang, Pengfei
-
p. 5396 - 5399
(2016/11/06)
-
- A practical in situ generation of the schwartz reagent. reduction of tertiary amides to aldehydes and hydrozirconation
-
A new, highly efficient in situ protocol (Cp2ZrCl2/LiAlH(OBu-t)3) is described for the generation of the Schwartz reagent which provides a convenient method for the amide to aldehyde reduction and the regioselective hydrozirconation-iodination of alkynes and alkenes. Highlighted are chemoselective reductions of benzamides derived by directed ortho metalation (DoM) chemistry, allowing the synthesis of valuable 1,2,3-substituted benzaldehydes. The single-step, three-component process proceeds in a very short reaction time, shows excellent functional group compatibility, and uses inexpensive and long-storage stable reducing reagents.
- Zhao, Yigang,Snieckus, Victor
-
supporting information
p. 390 - 393
(2014/04/03)
-
- Aggregation-induced emission of GFP-like chromophores via exclusion of solvent-solute hydrogen bonding
-
The fluorescence of GFP-like chromophores in aqueous solutions is turned on upon forming aggregates or embedment in cell membranes as a result of exclusion of solvent-solute H-bonding. The Royal Society of Chemistry 2014.
- Tou, Sio-Lon,Huang, Guan-Jhih,Chen, Po-Cheng,Chang, Huan-Tsung,Tsai, Jun-Yun,Yang, Jye-Shane
-
p. 620 - 622
(2014/01/06)
-
- IMIDAZOTRIAZINONE COMPOUNDS
-
The present invention provides imidazotriazinone compounds which are inhibitors of phosphodiesterase 9 and pharmaceutically acceptable salt thereof. The present invention further provides processes, pharmaceutical compositions, pharmaceutical preparations and pharmaceutical use of the compounds in the treatment of PDE9 associated diseases or disorders in mammals, including humans.
- -
-
Paragraph 0571; 0572; 0733; 0734
(2013/10/08)
-
- Site-selective hydrogen-bonding-induced fluorescence quenching of highly solvatofluorochromic GFP-like chromophores
-
The unconstrained green fluorescence protein (GFP)-like chromophore m-DMABDI displays a high solvatofluorochromicity in aprotic solvents, but the fluorescence is quenched in protic solvents. According to the site-specific intramolecularly hydrogen-bonded analogs 1OH and 2OH, the hydrogen bonding to the carbonyl oxygen is more important than that to the imino nitrogen of the imidazolinone group in the fluorescence quenching.
- Huang, Guan-Jhih,Ho, Jinn-Hsuan,Prabhakar, Ch.,Liu, Yi-Hung,Peng, Shie-Ming,Yang, Jye-Shane
-
supporting information
p. 5034 - 5037
(2013/01/15)
-
- Ferritin-supported palladium nanoclusters: Selective catalysts for aerobic oxidations in water
-
Confinement of nanometallic Pd within the core of a hyperthermophilic ferritin cage (from Pyrococcus furiosus) is reported. The resulting nanostructured hybrid catalysts can be used for highly specific aerobic oxidation of alcohols in water. This journal is
- Kanbak-Aksu,Nahid Hasan,Hagen,Hollmann,Sordi,Sheldon,Arends
-
supporting information; experimental part
p. 5745 - 5747
(2012/08/29)
-
- Emission wavelength prediction of a full-color-tunable fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one
-
In this paper we report on a novel fluorescent core skeleton, 9-aryl-1,2-dihydropyrrolo[3,4-b]indolizin-3-one, which we named Seoul-Fluor, having tunable and predictable photophysical properties. Using a concise and practical one-pot synthetic procedure, a 68-member library of new fluorescent compounds was synthesized with diverse substituents. In Seoul-Fluor, the electronic characteristics of the substituents, as well as their positional changes, have a close correlation with their photophysical properties. The systematic perturbation of electronic densities on the specific positions of Seoul-Fluor, guided with the Hammett constant, allows emission wavelength tunability covering the full color range. On the basis of these observations and a computational analysis, we extracted a simple first-order correlation of photophysical properties with the theoretical calculation and accurately predicted the emission wavelength of Seoul-Fluors through the rational design. In this study, we clearly demonstrate that Seoul-Fluor can provide a powerful gateway for the generation of desired fluorescent probes without the need for a tiresome synthesis and trial-and-error process.
- Kim, Eunha,Koh, Minseob,Lim, Byung Joon,Park, Seung Bum
-
supporting information; experimental part
p. 6642 - 6649
(2011/06/19)
-
- Biooxidation of Primary Alcohols to Aldehydes through Hydrogen Transfer Employing Janibacter terrae
-
Chemoselective oxidations still represent a challenge for chemists. Lyophilized cells of Janibacter terrae were employed for the chemoselective oxidation of primary alcohols to the corresponding aldehydes by hydrogen transfer with the use of acetaldehyde as the hydrogen acceptor. Secondary alcohol moieties were transformed at a much slower rate. The substrate spectrum encompasses substituted benzyl alcohols, whereby substrates with a substituent in the meta position were well tolerated, whereas only very small substituants were tolerated in the ortho position. Furthermore, nalkanols and allylic alcohols were transformed with good conversions. The biocatalyst was compatible with DMSO as a water miscible organic solvent up to 30 % v/v.
- Orbegozo, Thomas,De Vries, Johannes G.,Kroutil, Wolfgang
-
experimental part
p. 3445 - 3448
(2010/09/05)
-
- Schwartz Reagents: Methods of In Situ Generation and Use
-
Embodiments of the invention provide a method of using Schwartz Reagent, Cp2Zr(H)Cl, without accumulating or isolating it. Methods provide mixtures of Cp2ZrCl2, reductants that selectively reduce Cp2ZrCl2, and substrates. After reaction of Cp2ZrCl2 and the reductant, an intermediate reduction product is formed, apparently Schwartz Reagent. The in situ Schwartz Reagent then selectively reduces certain functional groups on the substrate. Substrates include tertiary amides, tertiary benzamides, aryl O-carbamates, and heteroaryl N-carbamates, which are reduced to aldehydes, benzaldehydes, aromatic alcohols, and heteroaromatics, respectively. Compared to prior methods, reagents are inexpensive and stable, reaction times are short, and reaction temperature in certain cases is conveniently room temperature. It has been estimated that using the in situ method described herein instead of synthesized or commercially obtained Schwartz Reagent provides a 50% reduction in cost.
- -
-
Page/Page column 7; 12
(2010/06/19)
-
- BETA-SECRETASE INHIBITING COMPOUNDS HAVING OXO-DIHYDRO-PYRAZOLE MOIETY
-
Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amo
- -
-
Page/Page column 36-37
(2009/04/25)
-
- BETA-SECRETASE INHIBITING COMPOUNDS
-
Disclosed are compounds represented by Formula (I) as defined in the specification, or pharmaceutically acceptable salts or isomers thereof, and a pharmaceutical composition for inhibiting beta-secretase activity comprising a therapeutically effective amount of the same.
- -
-
Page/Page column 58
(2009/04/25)
-
- Synthesis of photosynthesis-inhibiting nostoclide analogues
-
A series of 34 3-benzyl-5-(arylmethylene)furan-2(5H)-ones, designed using the naturally occurring toxins nostoclides as a lead structure, was synthesized as potential inhibitors of the photosynthetic electron transport. All compounds were fully characterized by IR, NMR (1H and 13C), and MS spectrometry. HMBC and HSQC bidimensional experiments allowed 13C and 1H assignments. Their biological activities were evaluated in vitro as the ability to interfere with light-driven reduction of ferricyanide by isolated spinach chloroplasts. About two-thirds of the compounds exhibited inhibitory properties in the micromolar range against the basal electron flow from water to K3[Fe(CN)6]. The inhibitory potential of these 3-benzyl-5-(arylmethylene)furan-2(5H)-one lactones is higher than that of other nostoclide analogues previously synthesized in the same laboratories.
- Teixeira, Robson R.,Barbosa, Luiz C. A.,Forlani, Giuseppe,Pilo-Veloso, Dorila,Carneiro, Jose Walkimar De Mesquita
-
experimental part
p. 2321 - 2329
(2009/12/29)
-
- Synthesis and study of novel benzothiazole derivatives with potential nonlinear optical properties
-
The synthesis of new benzothiazole push-pull systems as candidates for NLO-phores is described. Spectral (UV/VIS and solvatochromic) and theoretical studies (electronic properties based on semiempirical AM1 and PM3 methods) of the prepared compounds were carried out. The structure and physico-chemical parameters affecting the push-pull character and intramolecular charge transfer (ICT) of the studied compounds have been investigated and compounds with enhanced hyperpolarizability β have been predicted. The benzothiazolium salts were found to be much more effective NLO-phores in comparison with the corresponding neutral benzothiazoles. The 4-NPh2 group is the most effective donor. The extension of conjugated bridge improves the studied NLO characteristics. An additional acceptor group bonded to the heterocycle causes a red shift of λmax but does not increase hyperpolarizability.
- Sigmundova, Ivica,Zahradnik, Pavol,Loos, Dusan
-
p. 1069 - 1093
(2008/12/22)
-
- Quinoline synthesis: Scope and regiochemistry of photocyclisation of substituted benzylidenecyclopentanone O-alkyl and O-acetyloximes
-
Irradiation of substituted 2-benzylidenecyclopentanone O-alkyl and O-acetyloximes in methanol provides a convenient synthesis of alkyl, alkoxy, hydroxy, acetoxy, amino, dimethylamino and benzo substituted annulated quinolines. para-Substituents yield 6-substituted-2,3-dihydro-1H-cyclopenta[b] quinolines with 8-substituted products being obtained from ortho-substituted starting materials. Reactions of meta-substituted precursors are highly regioselective, with alkyl substituents leading to 5-substituted 2,3-dihydro-1H-cyclopenta[b]quinolines and more strongly electron-donating substituents generally resulting in 7-substituted products. 2-Furylmethylene and 2-thienylmethylene analogues yield annulated furo- and thieno-[2,3e]pyridines respectively. Sequential E- to Z-benzylidene group isomerisation and six π-electron cyclisation steps result in formation of a short-lived dihydroquinoline intermediate which spontaneously aromatises by elimination of an alcohol or acetic acid. For 2-benzylidenecyclopentanone O-allyloxime, singlet excited states are involved in both steps. The Royal Society of Chemistry 2007.
- Austin, Mark,Egan, Oliver J.,Tully, Raymond,Pratt, Albert C.
-
p. 3778 - 3786
(2008/10/09)
-
- Inhibitors of semicarbazide-sensitive amine oxidase (SSAO) and VAP-1 mediated adhesion useful for treatment and prevention of diseases
-
Compositions and methods of using compositions for treatment of inflammatory diseases and immune disorders are provided. Allylamino compounds are disclosed which are inhibitors of semicarbazide-sensitive amine oxidase (SSAO) and/or vascular adhesion protein 1 (VAP-1). The compounds have therapeutic utility in suppressing inflammation and inflammatory responses, and in treatment of several disorders, including multiple sclerosis and stroke.
- -
-
Page/Page column 69
(2008/06/13)
-
- NOVEL SULFONE AMIDE DERIVATIVES CAPABLE OF INHIBITING BACE
-
The present invention relates to novel derivatives of sulfone amide of Formula 1 as defined in this disclosure which inhibit the activity of BACE (or beta-secretase). These sulfone amide derivatives are useful for the treatment and prevention of Alzheimer's disease and related diseases caused by production of beta-amyloid, by inhibiting the activity of BACE.
- -
-
Page/Page column 192
(2010/02/11)
-
- Fluorescence sensing based on cation-induced conformational switching: Copper-selective modulation of the photoinduced intramolecular charge transfer of a donor-acceptor biphenyl fluorophore
-
The fluorescence emission energy of donor-acceptor substituted biphenyls is highly sensitive towards conformational changes of the interannular twist angle. By integrating 4-dimethylamino-4′-cyano-biphenyl into the ligand backbone of a thioether-rich metal receptor we designed a fluorescence sensor that exhibits high selectivity towards copper. Upon metal binding the ligand undergoes a significant conformational change, which induces a strong hypsochromic shift of the photoinduced charge-transfer emission. Steady-state absorption and fluorescence spectroscopy revealed a high affinity towards Cu(I) with a well-defined 1:1 metal-ligand complex stoichiometry. The nature of the conformational changes upon Cu(I) coordination were analyzed in detail by 1H NMR and 2D NOESY experiments. The spectroscopic data provide a coherent picture, which is consistent with a Boltzmann ground-state distribution of several rotamers that are locked into a more flattened geometry upon coordination of Cu(I).
- Cody, John,Fahrni, Christoph J.
-
p. 11099 - 11107
(2007/10/03)
-
- Controlled photochemical release of nitric oxide from O2-benzyl-substituted diazeniumdiolates
-
An investigation of potential photosensitive protecting groups for diazeniumdiolates (R2N-N(O)=NO-) has been initiated, and here the effect of meta electron-donating groups on the photochemistry of O2-benzyl-substituted diazeniumdiolates (R2N-N(O)=NOCH2Ar) is reported. Photolysis of the parent benzyl derivative (Ar = Ph) results almost exclusively in undesired photochemistry-the formation of nitrosamine and an oxynitrene intermediate with very little, if any, photorelease of the diazeniumdiolate. We have been able to use meta substitution to tune the photochemistry of these benzylic systems. The desired diazeniumdiolate photorelease has been shown to become more substantial with stronger π-donating meta substituents. This effect has been verified by direct observation of the photoreleased diazeniumdiolate with 1H NMR spectroscopy and by NO quantification measurements conducted in high- and low-ph solutions. In addition, the observed rates of NO release are consistent with that expected for normal thermal decomposition of the diazeniumdiolate in aqueous solutions and also show the same pH dependence.
- Ruane, Patrick H.,Bushan, K. Mani,Pavlos, Christopher M.,D'Sa, Raechelle A.,Toscano, John P.
-
p. 9806 - 9811
(2007/10/03)
-
- Synthesis and structural analysis of 1,4-bis[n-(N,N-di-methylamino)phenyl]buta-1,3-diynes and charge-transfer complexes with TCNE
-
n-(N,N-Dimethylamino)phenylethynes were satisfactorily prepared by a Wittig reaction between chloromethylene(triphenyl)phosphine ylide and the appropriate n-(N,N-dimethylamino)benzaldehyde, followed by dehydrochlorination with a strong base. The conjugate
- Rodriguez, J. Gonzalo,Lafuente, Antonio,Martin-Villamil, Rosa,Martinez-Alcazar, M. Paz
-
p. 859 - 868
(2007/10/03)
-
- Design, preparation, and electronic structure of high-spin cation diradicals derived from amine-based spin-polarized donors
-
Amine-based donor radicals, such as dimethylamino-, diethylamino-and morpholinonitronyl nitroxides, were synthesized, and their donor abilities were examined by cyclic voltammetry. ESR spectra of the singly oxidized donor radicals showed ground state triplet signals derived from the cation radicals of these donor radicals. The result was interpreted by the presence of the ferromagnetic coupling between the generated π-spin and the localized unpaired electron on the radical unit. According to the molecular orbital calculations, the ferromagnetic coupling between these two spins is originated from the space-sharing nature between SOMO which is localized on the radical unit and SOMO' which is derived from HOMO of the donor radical upon one-electron oxidation. Therefore, the cation-radicals of these donor radicals can be regarded as a heteroanalogue of trimethylenemethane. p-and m-dimethylaminophenyl nitronyl nitroxides were synthesized in order to expand the π-electronic structure of the donor unit, and the singly oxidized species were also found to afford triplet ESR signals. The origin of the ferromagnetic coupling of these aminophenyl nitronyl nitroxides was discussed on the same basis. Charge transfer complexes of some of the donor radicals with chloranil or 2,3-dichloro5,6-dicyano-1,4-benzoquinone were prepared, and the conducting and magnetic properties were examined.
- Sakurai, Hiromi,Izuoka, Akira,Sugawara, Tadashi
-
p. 9723 - 9734
(2007/10/03)
-
- PHARMACOLOGICALLY ACTIVE TRIAZINONES
-
The compounds are substituted 1,2,4-triazin-5-ones which are histamine H 2-antagonists. Two specific compounds of the present invention are 3-2-(5-methyl-4-imidazolylmethylthio)ethylamino!-6-(3-methoxybenzyl)-1,2, 4-tr iazin-5-one and 3-2-(5-methyl-4-imidazolylmethylthio)ethylamino!-6-(3-pyridylmethyl)-1,2,4-tr iazin-5-one.
- -
-
-