- Effect of partial hydrogenation on the phase behavior of poly(isoprene-b-styrene-b-methyl methacrylate) triblock copolymers
-
We studied the effect of selective hydrogenation of the polyisoprene block in poly(isoprene-b-styrene-b-methyl methacrylate) (ISM) triblock copolymers on nanoscale network phase formation. The morphologies of the resulting poly((ethylene-alt-propylene)-b-styrene-b-methyl methacrylate) (EPSM) triblock copolymers and several EPSM copolymer/homopolymer blends were investigated using a combination of small-angle X-ray scattering and transmission electron microscopy, where well-ordered HEX, SA, and Q230 (network) nanostructures were identified. Variations in the nanoscale morphologies and phase boundaries between EPSM copolymers and their corresponding ISM precursors can be attributed to the differences in conformational asymmetry and block interactions. Of particular interest, the growth in the gyroid network region in the EPSM relative to the ISM is highlighted as the expansion of this region could further enable the creation of network-forming nanoporous membranes made from materials that are expected to demonstrate improved resistance against thermal and oxidative degradation.
- Tureau, Maeva S.,Epps, Thomas H.
-
-
Read Online
- Anthracene Heme Cyclophanes. Steric Effects in CO, O2, and RNC Binding
-
Equilibrium constants in benzene solution are reported for binding of imidazoles, CO, O2, and isocyanide to two anthracene heme cyclophanes, Fe(6,6-cyclophane) and Fe(7,7-cyclophane), containing a conformationally mobile anthracene ring strapped symmetrically over the heme.The Fe(6,6-cyclophane) shows an approximately 300-fold reduction in affinity for the diatomic molecules, CO, and O2 compared to unhindered hemes.The Fe(7,7-cyclophane) shows only slight steric effects toward CO and O2 but larger effects with bulky isocyanides.The sizes of the cyclophane cavities are qualitatively probed with isocyanides of varying size.Kinetic data for binding of CO, O2, and tosylmethyl isocyanide to heme cyclophanes when compared to similar data for flat analogues demonstrate that steric effects are manifested primarily in the ligand association rates.This feature of the cyclophane is very similar to observed steric effects in hemoproteins, suggesting that large conformational changes (tilting of the cyclophane cap in the models and movement of distal protein residues in hemoproteins) occur in both prior to the transition state for ligation.Magnitudes of steric effects in hemoproteins and cyclophanes are calculated on the basis of comparison with the unhindered chelated heme model compounds.The nature of the distal steric effect in the Fe(6,6-cyclophane) model compound suggests that the reported bending or tilting of CO in hemoglobins and myoglobin may be of minor chemical significance.
- Traylor, T. G.,Tsuchiya, Shinji,Campbell, Dwane,Mitchell, Michael,Stynes, Dennis,Koga, Noboru
-
-
Read Online
- Photoredox Catalyzed Sulfonylation of Multisubstituted Allenes with Ru(bpy)3Cl2 or Rhodamine B
-
A highly regio- and stereoselective sulfonylation of allenes was developed that provided direct access to α, β-substituted unsaturated sulfone. By means of visible-light photoredox catalysis, the free radicals produced by p-toluenesulfonic acid reacted with multisubstituted allenes to obtain Markovnikov-type vinyl sulfones with Ru(bpy)3Cl2 or Rhodamine B as photocatalyst. The yield of this reaction could reach up to 91%. A series of unsaturated sulfones would be used for further transformation to some valuable compounds.
- Chen, Jingyun,Chen, Shufang,Jiang, Jun,Lu, Qianqian,Shi, Liyang,Xu, Zekun,Yimei, Zhao
-
supporting information
(2021/11/09)
-
- Styrene sulfone NLRP3 inflammasome inhibitor, preparation method and application thereof
-
The invention relates to the field of styrene sulfone compounds and NLRP3 inhibitors, and particularly provides a styrene sulfone NLRP3 inflammasome inhibitor, a preparation method and application thereof, wherein the inhibitor is represented by a formula (1), n is selected from 0 and 1, X is selected from N and O, R1 is selected from different electron withdrawing or electron donating substituents, and R2 is selected from different fat or aromatic substituents. According to the invention, it is verified that the compounds represented by the general formula have NLRP3 inhibitory activity.
- -
-
Paragraph 0053; 0064-0065
(2020/10/30)
-
- Visible-Light-Induced Radical Cascade Cyclizations of 1,7-Enynes with Sulfinic Acids: Direct Access to Sulfonated Chromanes and Sulfonated Tetrahydroquinolines under Metal-Free Conditions
-
Visible-light-induced strategy to access sulfonated chromanes and sulfonated 1,2,3,4-tetrahydroquinolines via a radical cascade cyclization of 1-(arylethynyl)-2-(vinyloxy)benzenes and N-allyl-2-(arylethynyl)anilines with aromatic and aliphatic sulfinic acids has been developed. In the presence of TBHP (7.5 mol%) as an oxidant and Eosin Y (3.0 mol%) as a photocatalyst, the reactions undergo smoothly to afford the corresponding products in good yields at room temperature under metal-free conditions. This transformation features low loading of TBHP, mild reaction conditions, simple operation, broad functional-group tolerance, and good yields of products. (Figure presented.).
- Liu, Qi,Mei, Yousheng,Wang, Lei,Ma, Yongmin,Li, Pinhua
-
supporting information
p. 5669 - 5680
(2020/10/28)
-
- Water-Promoted Dehydrative Tsuji–Trost Reaction of Non-Derivatized Allylic Alcohols with Sulfinic Acids
-
A mild, green and extra activator-free synthesis of allylic sulfones from non-derivatized allylic alcohols and sulfinic acids was developed and only the easily-available Pd(PPh3)4 was used as the catalyst. This new method could be easily scaled up to gram scale, affording the target allylic sulfones in a nearly quantitative yield with water as the sole by-product. Mechanism studies both by various NMR techniques and by theoretical calculations suggested two reaction pathways may be involved in the reaction, which are dependent on the reaction media, that is, an eight-membered ring binding species may be formed in aqueous media between allylic alcohol, sulfinic acid and water, while a six-membered ring binding species may be formed in common aprotic organic solvent between allylic alcohol and sulfinic acid. Both binding species may be accounted for the efficient activation of allylic alcohols via hydrogen bonding.
- Yu, Jing,Chang, Xueping,Ma, Ruitian,Zhou, Qiuju,Wei, Mengmeng,Cao, Xinhua,Ma, Xiantao
-
supporting information
p. 7238 - 7242
(2020/10/30)
-
- Sustainable access to sulfonic acids from halides and thiourea dioxide with air
-
A sustainable and mild one-step strategy is explored for the synthesis of aryl and alkyl sulfonic acids using a facile combination of halides and sulfur dioxide surrogates under air. The cheap industrial material thiourea dioxide was employed as an eco-friendly and easy-handling sulfur dioxide surrogate, while air was used as a green oxidant. Both aryl and alkyl sulfonic acids were obtained under transition metal-catalyzed or transition metal-free conditions. Mechanistic studies demonstrated that sulfinate was involved as an intermediate in this transformation. Notably, this protocol has been applied to the late-stage sulfonation of the drugs naproxen, isoxepac and ibuprofen.
- Zhang, Hui,Wang, Ming,Jiang, Xuefeng
-
supporting information
p. 8238 - 8242
(2020/12/29)
-
- Synergistic combination of visible-light photo-catalytic electron and energy transfer facilitating multicomponent synthesis of β-functionalized α,α-diarylethylamines
-
A synthetic strategy with the visible-light photo-catalytic synergistic combination of electron and energy transfer processes has been developed. The mild reaction conditions allow the radical-radical cross-coupling phenomenon for the multicomponent synthesis of β-arylsulfonyl(diarylphosphinoyl)-α,α-diarylethyl-amines from readily available arylsulfinic acids (diarylphosphine oxides), 1,1-diarylethylenes and arylazides.
- Wu, Yanan,Zhang, Yipin,Jiang, Mingjie,Dong, Xunqing,Jalani, Hitesh B.,Li, Guigen,Lu, Hongjian
-
p. 6405 - 6408
(2019/06/07)
-
- Organocatalytic Transformation of Aldehydes to Thioesters with Visible Light
-
A metal- and oxidant-free catalytic method for accessing structurally diverse thioesters from readily accessible, widespread aldehydes, is described. A strategy of a simple organic 9,10-phenanthrenequinone-promoted hydrogen atom transfer (HAT) with visible light was successfully implemented to selectively generate acyl radicals without inducing crossover reactivity of thioester products. The preparative power of the method was demonstrated by broad substrate scope and wide functional group tolerance, and enabled the late-stage modification of complex structures, which are difficult to achieve with the existing protocols.
- Zhang, Yueteng,Ji, Peng,Hu, Wenbo,Wei, Yongyi,Huang, He,Wang, Wei
-
supporting information
p. 8225 - 8228
(2019/07/16)
-
- Efforts towards an On-Target Version of the Groebke–Blackburn–Bienaymé (GBB) Reaction for Discovery of Druglike Urokinase (uPA) Inhibitors
-
Target-guided synthesis (TGS) has emerged as a promising strategy in drug discovery. Although reported examples of TGS generally involve two-component reactions, there is a strong case for developing target-guided versions of three-component reactions (3CRs) because of their potential to deliver highly diversified druglike molecules. To this end, the Groebke–Blackburn–Bienaymé reaction was selected as a model 3CR. We recently reported a series of druglike urokinase inhibitors, and these serve as reference compounds in the present study. Due to the limited number of literature reports on target-guided 3CRs, multiple experimental parameters were optimized here. Most challenging was the formation of imine intermediates under near-physiological conditions. This aspect was addressed by exploring chemical imine stabilization strategies. Notably, imines are also crucial intermediates of other 3CRs. Such systematic studies are strongly required for further development of the TGS domain but are largely absent in the literature. Hence, this work is intended as a reference for future multicomponent-based TGS studies.
- Gladysz, Rafaela,Vrijdag, Johannes,Van Rompaey, Dries,Lambeir, Anne-Marie,Augustyns, Koen,De Winter, Hans,Van der Veken, Pieter
-
supporting information
p. 12380 - 12393
(2019/09/06)
-
- Novel Compounds Targeting the RNA-Binding Protein HuR. Structure-Based Design, Synthesis, and Interaction Studies
-
The key role of RNA-binding proteins (RBPs) in regulating post-transcriptional processes and their involvement in several pathologies (i.e., cancer and neurodegeneration) have highlighted their potential as therapeutic targets. In this scenario, Embryonic Lethal Abnormal Vision (ELAV) or Hu proteins and their complexes with target mRNAs have been gaining growing attention. Compounds able to modulate the complex stability could constitute an innovative pharmacological strategy for the treatment of numerous diseases. Nevertheless, medicinal-chemistry efforts aimed at developing such compounds are still at an early stage. As part of our ongoing research in this field, we hereby present the rational design and synthesis of structurally novel HuR ligands, potentially acting as HuR-RNA interferers. The following assessment of the structural features of their interaction with HuR, combining saturation-transfer difference NMR and in silico studies, provides a guide for further research on the development of new effective interfering compounds of the HuR-RNA complex.
- Della Volpe, Serena,Nasti, Rita,Queirolo, Michele,Unver, M. Yagiz,Jumde, Varsha K.,D?mling, Alexander,Vasile, Francesca,Potenza, Donatella,Ambrosio, Francesca Alessandra,Costa, Giosué,Alcaro, Stefano,Zucal, Chiara,Provenzani, Alessandro,Di Giacomo, Marcello,Rossi, Daniela,Hirsch, Anna K. H.,Collina, Simona
-
supporting information
p. 615 - 620
(2019/04/25)
-
- The base-free van Leusen reaction of cyclic imines on water: Synthesis of N-fused imidazo 6,11-dihydro β-carboline derivatives
-
Construction of imidazoles has been demonstrated on water under base-free conditions. The reaction of dihydro β-carboline imines and p-toluenesulfonylmethyl isocyanides furnished the corresponding substituted N-fused imidazo 6,11-dihydro β-carboline derivatives in very good yields under ambient conditions. The use of deuterium oxide (D2O) as a solvent enabled the incorporation of deuterium isotopes in the imidazole ring.
- Satyam, Killari,Murugesh,Suresh, Surisetti
-
supporting information
p. 5234 - 5238
(2019/06/07)
-
- 4—(1H— IMIDAZOL— 5— YL) -1H-PYRROLO [2, 3-B] PYRIDINES FOR USE IN THE TREATMENT OF LEUKAEMIAS, LYMPHOMAS AND SOLID TUMORS
-
The present invention relates to novel 4-(1H-imidazol-5-yl)-1H-pyrrolo[2,3-b]pyridine compounds which are useful in the treatment of lymphomas, leukaemias, and solid tumors.
- -
-
Page/Page column 99-100
(2019/10/23)
-
- Catalyst-free sulfenylation of indoles with sulfinic esters in ethanol
-
A novel catalyst-free method for the synthesis of structurally diverse indole thioethers in moderate to excellent yields has been developed. In this reaction, sulfinic esters serve as new sulfur electrophiles.
- Yang, Xiuqin,Bao, Yishu,Dai, Zonghao,Zhou, Qingfa,Yang, Fulai
-
p. 3727 - 3731
(2018/08/21)
-
- NOVEL SUBSTITUTED SULFOXIMINE COMPOUNDS
-
The present invention relates to novel heterocyclic compounds of the general formula (I) their pharmaceutically acceptable salts, pharmaceutically acceptable solvates, enantiomers, diastereomers and polymorphs. The invention also relates to processes for the preparation of the compounds of invention, pharmaceutical compositions containing the compounds and their use as the compounds of the invention belong to the family of NOD-like receptor family (NLR) protein NLRP3 modulators. The present invention thus relates to novel NLRP3 modulators as well as to the use of the novel inhibitor compounds in the treatment of diseases or conditions as well as treatment of disease states mediated by NLRP3 as well as treatment of diseases or conditions in which interleukin 1β activity and interleukin-18 (IL-18) is implicated.
- -
-
Page/Page column 16; 17
(2019/01/06)
-
- Direct Substitution of Secondary and Tertiary Alcohols to Generate Sulfones under Catalyst- and Additive-Free Conditions
-
An environmentally benign protocol that affords propargylic sulfones containing highly congested carbon centers from easily accessible alcohols and sulfinic acids with water as the only byproduct is reported. The reaction proceeded via an in situ dehydrative cross-coupling process by taking advantage of the synergetic actions of multiple hydrogen bonds rather than relying on an external catalyst and/or additives to achieve high product distribution.
- Liu, Yanan,Xie, Peizhong,Sun, Zuolian,Wo, Xiangyang,Gao, Cuiqing,Fu, Weishan,Loh, Teck-Peng
-
p. 5353 - 5356
(2018/09/13)
-
- Catalytic Enantio- and Diastereoselective Mannich Addition of TosMIC to Ketimines
-
Chiral amines bearing a stereocenter in the α position are ubiquitous compounds with many applications in the pharmaceutical and agrochemical sectors, as well as in catalysis. Catalytic asymmetric Mannich additions represent a valuable method to access such compounds in enantioenriched form. This work reports the first enantio- and diastereoselective addition of commercially available p-toluenesulfonylmethyl isocyanide (TosMIC) to ketimines, affording 2-imidazolines bearing two contiguous stereocenters, one of which is fully-substituted, with high yields and excellent stereocontrol. The reaction, catalyzed by silver oxide and a dihydroquinine-derived N,P-ligand, is broad in scope, operationally simple, and scalable. Derivatization of the products provides enantioenriched vicinal diamines, precursors to NHC ligands and sp3-rich heterocyclic scaffolds. Computations are used to understand catalysis and rationalize stereoselectivity.
- Franchino, Allegra,Chapman, Jack,Funes-Ardoiz, Ignacio,Paton, Robert S.,Dixon, Darren J.
-
supporting information
p. 17660 - 17664
(2018/11/10)
-
- COMPOSITIONS FOR THE TREATMENT OF HYPERTENSION AND/OR FIBROSIS
-
The present invention relates to novel compounds and their use in the prophylactic and/or therapeutic treatment of hypertension and/or fibrosis.
- -
-
Paragraph 0099
(2018/04/20)
-
- Molecular Basis for the N-Terminal Bromodomain-and-Extra-Terminal-Family Selectivity of a Dual Kinase-Bromodomain Inhibitor
-
As regulators of transcription, epigenetic proteins that interpret post-translational modifications to N-terminal histone tails are essential for maintaining cellular homeostasis. When dysregulated, "reader" proteins become drivers of disease. In the case of bromodomains, which recognize N-?-acetylated lysine, selective inhibition of individual bromodomain-and-extra-terminal (BET)-family bromodomains has proven challenging. We describe the >55-fold N-terminal-BET bromodomain selectivity of 1,4,5-trisubstituted-imidazole dual kinase-bromodomain inhibitors. Selectivity for the BRD4 N-terminal bromodomain (BRD4(1)) over its second bromodomain (BRD4(2)) arises from the displacement of ordered waters and the conformational flexibility of lysine-141 in BRD4(1). Cellular efficacy was demonstrated via reduction of c-Myc expression, inhibition of NF-κB signaling, and suppression of IL-8 production through potential synergistic inhibition of BRD4(1) and p38α. These dual inhibitors provide a new scaffold for domain-selective inhibition of BRD4, the aberrant function of which plays a key role in cancer and inflammatory signaling.
- Divakaran, Anand,Talluri, Siva K.,Ayoub, Alex M.,Mishra, Neeraj K.,Cui, Huarui,Widen, John C.,Berndt, Norbert,Zhu, Jin-Yi,Carlson, Angela S.,Topczewski, Joseph J.,Schonbrunn, Ernst K.,Harki, Daniel A.,Pomerantz, William C. K.
-
p. 9316 - 9334
(2018/10/24)
-
- Design, synthesis, and biological evaluation of novel combretastatin A-4 thio derivatives as microtubule targeting agents
-
A series of novel combretastatin A-4 (CA-4) thio derivatives containing different molecular cores, namely α-phenylcinnamic acids (core 1), (Z)-stilbenes (core 2), 4,5-disubstituted oxazoles (core 3), and 4,5-disubstituted N-methylimidazoles (core 4), as cis-restricted analogues were designed and synthesized. They were selected with the use of a parallel virtual screening protocol including the generation of a virtual combinatorial library based on an elaborated synthesis protocol of CA-4 analogues. The selected compounds were evaluated for antiproliferative activity against a panel of six human cancer cell lines (A431, HeLa, MCF7, MDA-MB-231, A549 and SKOV) and two human non-cancer cell lines (HaCaT and CCD39Lu). Moreover, the effect of the test compounds on the inhibition of tubulin polymerization in vitro was estimated. In the series studied here, oxazole-bridged analogues exhibited the most potent antiproliferative activity. Compounds 23a, 23e, and 23i efficiently inhibited tubulin polymerization with IC50 values of 0.86, 1.05, and 0.85 μM, respectively. Thio derivative 23i, when compared to its oxygen analogue 23j, showed a 5-fold higher inhibitory impact on tubulin polymerization. Compounds 23e and 23i, which showed both best cytotoxic and antitubulin activity, were further studied in terms of their effect on cell cycle distribution and proapoptotic activity. Compound 23e induced a statistically significant block of the cell cycle at the G2/M phase in A431, HaCaT, HeLa, MCF-7, MDA-MB-231, and SKOV-3 cells to an extent comparable to that observed in CA-4. In HeLa and SKOV-3 cells incubated with 23i, a concentration-dependent block of the G2/M phase was observed. The proapoptotic effect of 23e and 23i in A431, HaCaT, MCF-7, MDA-MB-231, and SKOV-3 was demonstrated with ELISA assay and double staining with Annexin V-FITC/PI. The results indicated that compound 23e and 23i may serve as novel lead compounds in research on more effective anticancer agents.
- Stefański, Tomasz,Mikstacka, Renata,Kurczab, Rafa?,Dutkiewicz, Zbigniew,Kucińska, Ma?gorzata,Murias, Marek,Zielińska-Przyjemska, Ma?gorzata,Cichocki, Micha?,Teubert, Anna,Kaczmarek, Mariusz,Hogendorf, Adam,Sobiak, Stanis?aw
-
supporting information
p. 797 - 816
(2018/01/03)
-
- Method for synthesizing aryl sulfonic acid by utilizing sulfur dioxide
-
The invention relates to a method for synthesizing aryl sulfonic acid by utilizing sulfur dioxide. The method is characterized by comprising the following steps that S1, aromatic hydrocarbon is added into a solvent, stirring is performed to achieve complete dissolution, and then a catalyst is added; S2, under the stirring condition and the conditions of 0-100 DEG C and 0-10 atm, dried excessive sulfur dioxide gas or sulfur dioxide liquid are added, and reaction is performed for 0.5-50 hours; S3, the reaction liquid obtained in the step S2 is cooled to 10 DEG C or below, pressurized filtration is performed, and a catalyst is recovered; S4, filtrate is distilled to recover unreacted sulfur dioxide, then the solvent is recovered through distillation, the residual solid is the product aryl sulfonic acid, and the product yield is higher than 85%. The raw materials for the method for synthesizing the aryl sulfonic acid by utilizing the sulfur dioxide are cheap and easy to obtain, the product yield is high, the production process is safer, ad the severe environmental pollution of a traditional process is greatly reduced.
- -
-
Paragraph 0048-0052; 0071-0082
(2018/01/04)
-
- Visible-Light Photoredox Catalyzed Oxidative/Reductive Cyclization Reaction of N-Cyanamide Alkenes for the Synthesis of Sulfonated Quinazolinones
-
An efficient photocatalytic oxidative/reductive cyclization reaction of N-cyanamide alkenes with arylsulfinic acids or arylsulfonyl chlorides, which proceeds through C-S, C-C, and C-N bond formations, is reported. This photocatalytic reaction was carried out under mild conditions, which provides a new strategy for the synthesis of sulfonated quinazolinones. Furthermore, a one-pot procedure to achieve terminal alkenes has been explored via elimination of the obtained sulfonated quinazolinones under basic conditions.
- Qian, Ping,Deng, Yu,Mei, Haibo,Han, Jianlin,Zhou, Jie,Pan, Yi
-
supporting information
p. 4798 - 4801
(2017/09/23)
-
- Direct Irradiaton of Aryl Sulfides: Homolytic Fragmentation and Sensitized S-Oxidation
-
The direct irradiation of diphenyl sulfide and p-substituted thioanisoles in the presence of oxygen was investigated by means of both steady state and laser flash photolysis experiments. Two competitive pathways took place from the triplet excited state o
- Bonesi, Sergio M.,Crespi, Stefano,Merli, Daniele,Manet, Ilse,Albini, Angelo
-
p. 9054 - 9065
(2017/09/11)
-
- N-Hydroxy sulfonamides as new sulfenylating agents for the functionalization of aromatic compounds
-
An unprecedented use of N-hydroxy sulfonamides as sulfenylating agents has been established. In the presence of catalytic amounts of iodine and N-hydroxysuccinimide, N-hydroxy sulfonamides participated in sulfenylation with indoles, 7-azaindole, N-methyl pyrrole, and 2-naphthol to afford structurally diverse thioethers in moderate to excellent yields with very high regioselectivity.
- Wang, Fu-Xiang,Zhou, Shao-Da,Wang, Chengming,Tian, Shi-Kai
-
supporting information
p. 5284 - 5288
(2017/07/10)
-
- Thiocarbamate-based synthesis of 2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thiones
-
A five-step synthesis of 5,7-diaryl-substituted 2,4,5,6-tetrahydro-3H-1,2,4-triazepine-3-thiones starting from ethyl thiocarbamate was developed. The synthesis included a three-component condensation of ethyl thiocarbamate with aromatic aldehydes and p-toluenesulfinic acid to give O-ethyl[(aryl)(tosyl)methyl]thiocarbamates which were transformed into the corresponding O-ethyl (3-phenyl-3-oxopropyl) thiocarbamates by treatment with the sodium enolate of dibenzoylmethane followed by base-promoted retro-Claisen condensation. Reaction of the prepared thiocarbamates with hydrazine and subsequent acid-catalysed cyclisation of the derived 4-[(3-hydrazono-3-phenyl)prop-1-yl]semicarbazides gave the target triazepines.
- Trafimova, Ludmila A.,Zimin, Maxim O.,Shutalev, Anatoly D.
-
p. 149 - 156
(2017/03/27)
-
- Visible-Light Photocatalytic Bicyclization of 1,7-Enynes toward Functionalized Sulfone-Containing Benzo[a]fluoren-5-ones
-
A new visible-light photocatalytic arylsulfonylation and bicyclization of C(sp3)-tethered 1,7-enynes with sulfinic acids has been developed, delivering functionalized sulfone-containing benzo[a]fluoren-5-ones with generally good yields. This Eosin Y-catalyzed approach makes use of visible light as a safe and eco-friendly energy source to drive cascade cyclization reactions, resulting in continuous multiple bond-forming events including C–S and C–C bonds to efficiently construct polycyclic-linked alkyl aryl sulfones. (Figure presented.).
- Huang, Min-Hua,Zhu, Yi-Long,Hao, Wen-Juan,Wang, Ai-Fang,Wang, De-Cai,Liu, Feng,Wei, Ping,Tu, Shu-Jiang,Jiang, Bo
-
supporting information
p. 2229 - 2234
(2017/07/07)
-
- Nucleophile-Mediated Ring Expansion of 5-Acyl-substituted 4-Mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones in the Synthesis of 7-Membered Analogues of Biginelli Compounds and Related Heterocycles
-
A general six-step approach to alkyl 2-oxo-2,3,6,7-tetrahydro-1H-1,3-diazepine-5-carboxylates and 5-acyl-2,3,6,7-tetrahydro-1H-1,3-diazepin-2-ones based on the nucleophile-mediated ring expansion reaction of 5-functionalized 4-mesyloxymethyl-1,2,3,4-tetrahydropyrimidin-2-ones has been developed. Synthesis of the latter involved nucleophilic substitution of tosyl group in readily available N-[(2-benzoyloxy-1-tosyl)ethyl]urea with sodium enolates of β-oxoesters or 1,3-diketones, followed by dehydration or heterocyclization-dehydration of resulting products, removal of benzoyl protection, and conversion of hydroxymethyl group into mesyloxymethyl group. Conformations of the obtained tetrahydro-1H-1,3-diazepin-2-ones in solid state and solutions were established using X-ray diffraction and NMR spectroscopy. A plausible mechanism of tetrahydropyrimidine ring expansion based on DFT calculation at B3LYP/6-31+G(d,p) level and NMR monitoring experiments was discussed. The ring contraction reaction of methoxy- or phenylthio-diazepinones under acidic conditions resulted in the corresponding 3-functionalized 1-carbamoyl-1H-pyrroles.
- Fesenko, Anastasia A.,Grigoriev, Mikhail S.,Shutalev, Anatoly D.
-
p. 8085 - 8110
(2017/08/14)
-
- Harnessing Redox Cross-Reactivity to Profile Distinct Cysteine Modifications
-
Cysteine S-nitrosation and S-sulfination are naturally occurring post-translational modifications (PTMs) on proteins induced by physiological signals and redox stress. Here we demonstrate that sulfinic acids and nitrosothiols react to form a stable thiosulfonate bond, and leverage this reactivity using sulfinate-linked probes to enrich and annotate hundreds of endogenous S-nitrosated proteins. In physiological buffers, sulfinic acids do not react with iodoacetamide or disulfides, enabling selective alkylation of free thiols and site-specific analysis of S-nitrosation. In parallel, S-nitrosothiol-linked probes enable enrichment and detection of endogenous S-sulfinated proteins, confirming that a single sulfinic acid can react with a nitrosothiol to form a thiosulfonate linkage. Using this approach, we find that hydrogen peroxide addition increases S-sulfination of human DJ-1 (PARK7) at Cys106, whereas Cys46 and Cys53 are fully oxidized to sulfonic acids. Comparative gel-based analysis of different mouse tissues reveals distinct profiles for both S-nitrosation and S-sulfination. Quantitative proteomic analysis demonstrates that both S-nitrosation and S-sulfination are widespread, yet exhibit enhanced occupancy on select proteins, including thioredoxin, peroxiredoxins, and other validated redox active proteins. Overall, we present a direct, bidirectional method to profile select redox cysteine modifications based on the unique nucleophilicity of sulfinic acids.
- Majmudar, Jaimeen D.,Konopko, Aaron M.,Labby, Kristin J.,Tom, Christopher T. M. B.,Crellin, John E.,Prakash, Ashesh,Martin, Brent R.
-
supporting information
p. 1852 - 1859
(2016/03/01)
-
- Palladium(II)-Catalyzed Synthesis of Sulfinates from Boronic Acids and DABSO: A Redox-Neutral, Phosphine-Free Transformation
-
A redox-neutral palladium(II)-catalyzed conversion of aryl, heteroaryl, and alkenyl boronic acids into sulfinate intermediates, and onwards to sulfones and sulfonamides, has been realized. A simple Pd(OAc)2 catalyst, in combination with the sulfur dioxide surrogate 1,4-diazabicyclo[2.2.2]octane bis(sulfur dioxide) (DABSO), is sufficient to achieve rapid and high-yielding conversion of the boronic acids into the corresponding sulfinates. Addition of C- or N-based electrophiles then allows conversion into sulfones and sulfonamides, respectively, in a one-pot, two-step process.
- Deeming, Alex S.,Russell, Claire J.,Willis, Michael C.
-
supporting information
p. 747 - 750
(2016/02/27)
-
- Sulfination of alcohols with sodium sulfinates promoted by BF3·OEt2: An unexpected access
-
A BF3·OEt2-promoted direct substitution of various alcohols with sodium sulfinates affording sulfinates under mild conditions has been developed. Further reaction of the hydroxysteroids achieves the highly complex sulfinates in good yields, which are two potential pharmacophores routinely encountered in drug discovery.
- Huang, Mingming,Hu, Liangzhen,Shen, Hang,Liu, Qing,Hussain, Muhammad Ijaz,Pan, Jing,Xiong, Yan
-
supporting information
p. 1874 - 1879
(2016/04/19)
-
- TGF-Beta Inhibitors
-
Disclosed are imidazole and thiazole compounds, as well as pharmaceutical compositions and methods of use thereof. One embodiment is a compound having the structure and pharmaceutically acceptable salts, prodrugs and N-oxides thereof (and solvates and hydrates thereof), wherein X, A, Z, R1 and R′ are as described herein. In certain embodiments, a compound disclosed herein inhibits TGF-β, and can be used to treat disease by blocking TGF-β signaling.
- -
-
Paragraph 0973-0974
(2016/09/26)
-
- An efficient and stereoselective approach to 14-membered hexaaza macrocycles using novel semicarbazone-based amidoalkylation reagents
-
An efficient synthesis of hydrazones of 4-(3-oxobutyl)semicarbazides and 4-(3-oxobutyl)semicarbazones using novel semicarbazone-based amidoalkylation reagents, 1-arylidene-4-[(aryl)(tosyl)methyl]semicarbazides, has been developed. The synthesis involved reaction of the latter with the Na-enolate of acetylacetone, followed by a base-promoted retro-Claisen reaction and treatment of the obtained 4-(3-oxobutyl)semicarbazones with hydrazine or methylhydrazine. The prepared hydrazones were converted stereoselectively into 14-membered cyclic bis-semicarbazones under acidic conditions. Especially high selectivity (trans/cis ? 97:3) was observed upon the macrocyclization of 4-(3-oxobutyl)semicarbazone hydrazones. A plausible reaction pathway and the stereochemistry of this cyclization were discussed.
- Fesenko, Anastasia A.,Yankov, Alexander N.,Shutalev, Anatoly D.
-
supporting information
p. 5784 - 5787
(2016/12/06)
-
- Palladium-Catalyzed Coupling of Sulfonylhydrazones with Heteroaromatic 2-Amino-Halides (Barluenga Reaction): Exploring the Electronics of the Sulfonylhydrazone
-
This paper describes a new reactivity of the Pd-catalyzed coupling of 2-amino-3-bromo-aromatic and heteroaromatic compounds with sulfonylhydrazones (Barluenga reaction).The new catalyst system and modulation of the electronic nature of hydrazone that were needed for successful reaction are described herein.
- Tan, Hongyu,Houpis, Ioannis,Liu, Renmao,Wang, Youchu,Chen, Zhilong,Fleming, Matthew J.
-
p. 1044 - 1048
(2015/09/01)
-
- Highly selective pd-catalyzed intermolecular fluorosulfonylation of styrenes
-
A novel Pd-catalyzed intermolecular regio- and diastereoselective fluorosulfonylation of styrenes has been developed under mild conditions. This reaction exhibits a wide range of functional-group tolerance in styrenes and arylsulfinic acids to afford various β-fluoro sulfones. Preliminary mechanistic study reveals an unusual mechanism, in which a high-valent L2PdIIIF species side-selectively reacts with a benzylic carbon radical to deliver a C-F bond. This pathway is distinct from a previously reported radical fluorination reaction.
- Yuan, Zheliang,Wang, Hao-Yang,Mu, Xin,Chen, Pinhong,Guo, Yin-Long,Liu, Guosheng
-
supporting information
p. 2468 - 2471
(2015/03/04)
-
- Different modes of acid-catalyzed cyclization of 4-(γ-oxoalkyl)semicarbazide hydrazones: 7-membered versus 14-membered cyclic semicarbazones formation
-
Acid-catalyzed cyclization of 4-(γ-oxoalkyl)semicarbazide hydrazones has been studied. 7-Membered cyclic semicarbazones, 2,4,5,6-tetrahydro-3H-1,2,4-triazepin-3-ones, were obtained from the γ-phenyl-substituted semicarbazides, while the cyclization of the γ-methyl-substituted semicarbazides involved two molecules of the starting material to result in 14-membered cyclic bis-semicarbazones, 1,2,4,8,9,11-hexaazacyclotetradeca-7,14-diene-3,10-diones. The 4-(γ-oxoalkyl)semicarbazide hydrazones were prepared according to a four-step synthesis based on amidoalkylation of the sodium enolates of 1,3-diketones with ethyl N-(1-tosylalk-1-yl)carbamates followed by base-promoted retro-Claisen reaction and treatment of the obtained ethyl N-(γ-oxoalkyl)carbamates with hydrazine.
- Fesenko, Anastasia A.,Shutalev, Anatoly D.
-
p. 9528 - 9543
(2015/12/05)
-
- Amides in one pot from Carboxylic Acids and Amines via Sulfinylamides
-
An efficient method has been developed for the direct amidification of carboxylic acids via sulfinylamides preformed in situ by the reaction of pure amines with prop-2- ene-1-sulfinyl chloride. The method can be applied to aliphatic acids, including pivalic acid, aromatic acids, and primary and secondary amines. It is compatible with acids bearing unprotected alcohol, phenol, and ketone moieties and applicable to the synthesis of peptides. It does not induce their a-epimerization.
- Bai, Jianfei,Zambron, Bartosz K.,Vogel, Pierre
-
p. 604 - 607
(2014/04/03)
-
- Metal-free reductive cleavage of C-N and S-N bonds by photoactivated electron transfer from a neutral organic donor
-
A photoactivated neutral organic super electron donor cleaves challenging arenesulfonamides derived from dialkylamines at room temperature. It also cleaves a)ArC-NR and b)ArN-C bonds. This study also highlights the assistance given to these cleavage reactions by the groups attached to N in (a) and to C in (b), by lowering LUMO energies and by stabilizing the products of fragmentation. Radical fragmentations: Electron transfer from the photoactivated neutral electron donor 1 delivers high yields of S-N and C-N cleavage products for a range of nitrogen-containing species. These reactions proceed at room temperature and under mild reaction conditions in the absence of any metal reagents. DMF=N,N-dimethylformamide, Ts=4-toluenesulfonyl.
- O'Sullivan, Steven,Doni, Eswararao,Tuttle, Tell,Murphy, John A.
-
p. 474 - 478
(2014/01/23)
-
- One-pot α-amidosulfone-mediated variation of the pictet-Spengler tetrahydroisoquinoline synthesis, suitable for amide-type substrates
-
The development of Pictet-Spengler reactions from amide substrates is a challenging problem. We report here that the reaction between amide-type compounds (including carbamates, amides, ureas and diketopiperazines), aldehydes and p-toluenesulfinic acid constitutes an efficient method for the preparation of tetrahydroisoquinolines or pyrazino-[2,1-b]isoquinolines. Unlike previously known methods, this one-pot Pictet-Spengler protocol avoids the need for strong Lewis or Br?nsted acid catalysts.
- Arroyo, Francisco J.,López-Alvarado, Pilar,Ganesan,Menéndez, J. Carlos
-
p. 5720 - 5727
(2014/11/07)
-
- Three-component reactions of ketene dithioacetals, aldehydes, and arenesulfinic acids: Facile synthesis of allylic sulfones
-
A facile and efficient synthesis of allylic sulfones via sulfuric acid-mediated three-component reactions of easily available ketene dithioacetals, aldehydes, and arenesulfinic acids is presented. The reaction features low cost and good yields.
- Liang, Deqiang,Huang, Wenzhong,Yuan, Lin,Ma, Yinhai,Ouyang, Liping,Rao, Yuqin,Yang, Yuxian
-
supporting information
p. 1930 - 1937
(2014/07/07)
-
- Copper-mediated cascade synthesis of diaryl sulfones via the sandmeyer reaction
-
A convenient and efficient method for the copper-mediated cascade synthesis of diaryl sulfones via the Sandmeyer reaction has been developed. The protocol uses readily available aryl amines and arylsulfinic acids as the starting materials, isoamyl nitrite as the diazotizating reagent of the aryl amines, and the method shows mild reaction conditions and high tolerance towards various functional groups in the substrates. Georg Thieme Verlag Stuttgart New York.
- Yang, Xiaobo,Shi, Liangliang,Fu, Hua
-
supporting information
p. 847 - 852
(2014/04/17)
-
- One-step synthesis of racemic α-amino acids from aldehydes, amine components, and gaseous CO2 by the aid of a bismetal reagent
-
α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid can be divided into three basic components: an aldehyde, an amine, and carbon dioxide (CO2). We report herein that a one-step synthesis of α-amino acids has been successfully achieved from these three basic and inexpensive chemicals with a single operation, in which the mixture of an aldehyde, a sulfonamide, and gaseous CO2 was heated at 100 °C in the presence of Bu3Sn-SnBu3 and CsF. In this one-pot sequential protocol, two important intermediates (imine and α-amino stannane) are involved and the stannyl anion generated in situ plays a crucial role, particularly for the efficient stannylation of the imine in the presence of proton sources and for promoting retrostannylation of the undesired α-alkoxy stannane owing to its high stability and tolerance of the presence of proton sources. This methodology enabled the synthesis of a wide range of racemic arylglycine derivatives in high yields. Go retro! α-Amino acids are essential resources for human life and are highly useful as building blocks for organic synthesis. The core framework of an α-amino acid is retrosynthesized to an aldehyde, an amine, and carbon dioxide. A one-step synthesis of α-amin Copyright
- Mita, Tsuyoshi,Higuchi, Yuki,Sato, Yoshihiro
-
p. 1123 - 1128
(2013/02/23)
-
- The importance of hydrogen bonding and aromatic stacking to the affinity and efficacy of cannabinoid receptor CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl)methyl]-N-[(1S,2S,4R)-1,3, 3-trimethylbicyclo[2.2.1]hept-2-yl]-1H-pyrazole-3-carboxamide (SR144528)
-
Despite the therapeutic promise of the subnanomolar affinity cannabinoid CB2 antagonist, 5-(4-chloro-3-methylphenyl)-1-[(4-methylphenyl) methyl]-N-[(1S,2S,4R)-1,3,3-trimethylbicyclo[2.2.1]hept-2-yl] -1H-pyrazole-3-carboxamide (SR144528, 1), little is known about its binding site interactions and no primary interaction site for 1 at CB2 has been identified. We report here the results of Glide docking studies in our cannabinoid CB 2 inactive state model that were then tested via compound synthesis, binding, and functional assays. Our results show that the amide functional group of 1 is critical to its CB2 affinity and efficacy and that aromatic stacking interactions in the TMH5/6 aromatic cluster of CB2 are also important. Molecular modifications that increased the positive electrostatic potential in the region between the fenchyl and aromatic rings led to more efficacious compounds. This result is consistent with the EC-3 loop negatively charged amino acid, D275 (identified via Glide docking studies) acting as the primary interaction site for 1 and its analogues.
- Kotsikorou, Evangelia,Navas III, Frank,Roche, Michael J.,Gilliam, Anne F.,Thomas, Brian F.,Seltzman, Herbert H.,Kumar, Pritesh,Song, Zhao-Hui,Hurst, Dow P.,Lynch, Diane L.,Reggio, Patricia H.
-
p. 6593 - 6612
(2013/10/01)
-
- CARBOXAMIDE OR SULFONAMIDE SUBSTITUTED THIAZOLES AND RELATED DERIVATIVES AS MODULATORS FOR THE ORPHAN NUCLEAR RECEPTOR ROR[GAMMA]
-
The invention provides modulators for the orphan nuclear receptor RORy and methods for treating RORy mediated diseases by administering these novel RORy modulators to a human or a mammal in need thereof. Specifically, the present invention provides carboxamide or sulfonamide containing cyclic compounds of Formula (1), (1'), (100), (100'), (200) and (200') and the enantiomers, diastereomers, tautomers, /V-oxides, solvates and pharmaceutically acceptable salts thereof.
- -
-
Page/Page column 178; 179
(2014/01/07)
-
- A p-toluenesulfinic acid-catalyzed three-component Ugi-type reaction and its application for the synthesis of α-amino amides and amidines
-
A mild, cost-effective, and simple three-component Ugi-type reaction using p-toluenesulfinic acid (pTSIA) as the acid catalyst has been developed to synthesize α-amino amides and α-amino amidines. Employing 1 equiv of amine used in the reaction generated α-amino amides exclusively, while 2 equiv of amines, especially with more nucleophilic aniline such as p-anisidine, yielded the α-amino amidines as the major product. This methodology would be suitable for the synthesis of natural or unnatural amino acids and drug-like amidine analogues.
- Saha, Biswajit,Frett, Brendan,Wang, Yuanxiang,Li, Hong-Yu
-
p. 2340 - 2343
(2013/06/26)
-
- Microwave-accelerated Pd-catalyzed desulfitative direct C2-arylation of free (NH)-indoles with arylsulfinic acids
-
The rapid and efficient direct C2-arylation of free (NH)-indoles with arylsulfinic acids proceeded through a microwave-accelerated palladium-catalyzed desulfitation reaction. By using PdCl2 as a catalyst, silver acetate as an oxidant, and H2SO4 as an additive, arylsulfinic acids with both electron-donating and electron-withdrawing groups underwent desulfitative coupling with an array of free (NH)-indoles, thereby selectively providing C2-arylindoles in good yields. From C2 shining sea: The direct C2-arylation of free (NH)-indoles with arylsulfinic acids proceeded through a Pd-catalyzed desulfitation reaction. In the presence of an oxidant and an additive, 2-arylindoles were selectively afforded in good yields. Copyright
- Miao, Tao,Li, Pinhua,Wang, Guan-Wu,Wang, Lei
-
p. 3185 - 3190
(2014/01/06)
-
- Photopolymerization kinetics of α-disulfone cationic photoinitiator
-
An α-disulfone cationic photoinitiator called 4-tolyl methyl disulfone was synthesized and characterized by UV-vis absorption spectroscopy, LCMS, IR and NMR. Eight vinyl ether monomers were chosen to study the kinetics of photopolymerization by real-time infrared spectroscopy (FT-IR). It showed that 4-tolyl methyl disulfone was an effective cationic photoinitiator. The rate of polymerization and ultimate conversion increased with increase of 4-tolyl methyl disulfone concentration and light intensity.
- Chen, Hua,Yang, Jinliang,Guo, Dongfang,Wang, Liyuan,Nie, Jun
-
-
- Visible light-induced 3-sulfenylation of N-methylindoles with arylsulfonyl chlorides
-
The synthesis of 1-methyl-3-(arylthio)-1H-indoles has been achieved by the photoredox reaction of N-methylindoles with readily available arylsulfonyl chlorides in moderate yields.
- Chen, Min,Huang, Zhi-Tang,Zheng, Qi-Yu
-
supporting information
p. 11686 - 11688,3
(2012/12/12)
-
- Differentiation of diastereotopic bromine atoms in SN2 reactions of gem-dibromides
-
A novel directed SN2 reaction of conformationally biased gem-dibromides and an arenesulfinate anion is described. The reaction results in the diastereoselective formation of α-bromosulfones. The selectivity originates from pre-coordination of the nucleophile to a free hydroxyl group in the γ-position.
- Muenster, Niels,Harms, Klaus,Koert, Ulrich
-
supporting information; experimental part
p. 1866 - 1867
(2012/02/16)
-
- Palladium-catalyzed desulfitative heck-type reaction of aryl sulfinic acids with alkenes
-
An efficient protocol has been developed for the desulfitative Heck-type reaction of aryl sulfinic acids with a variety of alkenes in the presence of a catalytic amount of Pd(OAc)2 and inexpensive Cu(OAc)2 as oxidant. This method does not require a ligand or a base, thereby broadening the scope of Pd-catalyzed coupling reactions. Copyright
- Wang, Guan-Wu,Miao, Tao
-
supporting information; experimental part
p. 5787 - 5790
(2011/06/23)
-
- Synthesis of ketones by palladium-catalysed desulfitative reaction of arylsulfinic acids with nitriles
-
Palladium-catalysed desulfitative addition of arylsulfinic acids to aryl and alkyl nitriles with 2,2′-bipyridine as a ligand afforded a variety of aryl ketones via hydrolysis of ketimine intermediates.
- Miao, Tao,Wang, Guan-Wu
-
supporting information; experimental part
p. 9501 - 9503
(2011/10/01)
-
- Benzo[b]fluorenes via indanone dianion annulation. A short synthesis of prekinamycin
-
Figure presented A rapid construction of benzo[b]fluorenones via reaction of 1-indanone dianions with phthalate diesters is described. Its utility is illustrated with a concise synthesis of prekinamycin.
- Birman, Vladimir B.,Zhao, Zhufeng,Guo, Lei
-
p. 1223 - 1225
(2008/01/05)
-
