908072-33-3Relevant academic research and scientific papers
Alternating Cascade Metathesis Polymerization of Enynes and Cyclic Enol Ethers with Active Ruthenium Fischer Carbenes
Sui, Xuelin,Zhang, Tianqi,Pabarue, Alec B.,Fu, Liangbing,Gutekunst, Will R.
supporting information, p. 12942 - 12947 (2020/09/01)
Ruthenium alkoxymethylidene complexes have rarely been demonstrated as active species in metathesis reactions and are frequently regarded as inert. Herein, we highlight the ability of these Fischer-type carbenes to participate in cascade alternating ring-
Construction of a Shape-Diverse Fragment Set: Design, Synthesis and Screen against Aurora-A Kinase
Zhang, Rong,McIntyre, Patrick J.,Collins, Patrick M.,Foley, Daniel J.,Arter, Christopher,von Delft, Frank,Bayliss, Richard,Warriner, Stuart,Nelson, Adam
, p. 6831 - 6839 (2019/05/10)
Historically, chemists have explored chemical space in a highly uneven and unsystematic manner. As an example, the shape diversity of existing fragment sets does not generally reflect that of all theoretically possible fragments. To assess experimentally the added value of increased three dimensionality, a shape-diverse fragment set was designed and collated. The set was assembled by both using commercially available fragments and harnessing unified synthetic approaches to sp3-rich molecular scaffolds. The resulting set of 80 fragments was highly three-dimensional, and its shape diversity was significantly enriched by twenty synthesised fragments. The fragment set was screened by high-throughput protein crystallography against Aurora-A kinase, revealing four hits that targeted the binding site of allosteric regulators. In the longer term, it is envisaged that the fragment set could be screened against a range of functionally diverse proteins, allowing the added value of more shape-diverse screening collections to be more fully assessed.
A strategic approach to [6,6]-bicyclic lactones: Application towards the CD fragment of DHβE
Jepsen, Tue Heesgaard,Glibstrup, Emil,Crestey, Fran?ois,Jensen, Anders A.,Kristensen, Jesper Langgaard
supporting information, p. 988 - 994 (2017/06/20)
We report an effective synthetic protocol to access [6,6]-bicyclic lactone moieties through a regio- and stereoselective intramolecular Mizoroki–Heck cross-coupling reaction followed by a 6π-electrocyclization. This method enabled the first synthesis of t
Design, synthesis, biological evaluation and molecular docking of amide and sulfamide derivatives as Escherichia coli pyruvate dehydrogenase complex E1 inhibitors
He, Haifeng,Feng, Jiangtao,He, Junbo,Xia, Qin,Ren, Yanliang,Wang, Fang,Peng, Hao,He, Hongwu,Feng, Lingling
, p. 4310 - 4320 (2016/01/29)
In this study, a series of novel amide derivatives and sulfamide derivatives as potential E. coli PDHc E1 inhibitors were designed and synthesized by optimizing the linker between triazole and benzene ring moieties based on the structure of lead compound
Enantioselective Rhodium(I) Donor Carbenoid-Mediated Cascade Triggered by a Base-Free Decomposition of Arylsulfonyl Hydrazones
Torres, òscar,Parella, Teodor,Solà, Miquel,Roglans, Anna,Pla-Quintana, Anna
supporting information, p. 16240 - 16245 (2015/11/03)
The reaction of diyne arylsulfonyl hydrazone substrates under rhodium(I)/BINAP catalysis gives access to sulfonated azacyclic frameworks in a highly enantioselective manner. This new cascade process considerably increases the molecular complexity by generating two C-C bonds, one C-S bond, and one C-H bond. Theoretical calculations, competitive experiments, and deuterium labeling have jointly been used to propose a mechanism that accounts for the reaction. The mechanism involves the formation of vinyl rhodium carbenoids, hydride migratory insertion, and intermolecular stereoselective nucleophilic attack. The last two steps are the key to the stereoselectivity of the process.
Dual gold catalysis: A novel synthesis of bicyclic and tricyclic pyrroles from n -propargyl ynamides
Tokimizu, Yusuke,Wieteck, Marcel,Rudolph, Matthias,Oishi, Shinya,Fujii, Nobutaka,Hashmi, A. Stephen K.,Ohno, Hiroaki
supporting information, p. 604 - 607 (2015/03/05)
Various N-propargyl ynamides were converted to bicylic and tricyclic pyrroles by the use of a cationic dual-activation gold catalyst. This reaction starts with the nucleophilic addition of a gold acetylide onto an ynamide triple bond at the ?2-position of the nitrogen atom. Thus, gold vinylidene is formed, and then a second cyclization takes place. The formation of the gold vinylidene is indicated by the evidence that not only aryl ynamides but also alkyl ynamides undergo C-H activation in these reactions.
Mapping the protein interaction landscape for fully functionalized small-molecule probes in human cells
Kambe, Tohru,Correia, Bruno E.,Niphakis, Micah J.,Cravatt, Benjamin F.
supporting information, p. 10777 - 10782 (2014/08/18)
Phenotypic screening provides a means to discover small molecules that perturb cell biological processes. Discerning the proteins and biochemical pathways targeted by screening hits, however, remains technically challenging. We recently described the use of small molecules bearing photoreactive groups and latent affinity handles as fully functionalized probes for integrated phenotypic screening and target identification. The general utility of such probes, or, for that matter, any small-molecule screening library, depends on the scope of their protein interactions in cells, a parameter that remains largely unexplored. Here, we describe the synthesis of an ～60-member fully functionalized probe library, prepared from Ugi-azide condensation reactions to impart structural diversity and introduce diazirine and alkyne functionalities for target capture and enrichment, respectively. In-depth mass spectrometry-based analysis revealed a diverse array of probe targets in human cells, including enzymes, channels, adaptor and scaffolding proteins, and proteins of uncharacterized function. For many of these proteins, ligands have not yet been described. Most of the probe-protein interactions showed well-defined structure-activity relationships across the probe library and were blocked by small-molecule competitors in cells. These findings indicate that fully functionalized small molecules canvas diverse segments of the human proteome and hold promise as pharmacological probes of cell biology.
Alkynyl-coumarinyl ethers as MAO-B inhibitors
Mertens, Matthias D.,Hinz, Sonja,Müller, Christa E.,Gütschow, Michael
, p. 1916 - 1928 (2014/03/21)
In this study, alkynyl-coumarinyl ethers were developed as inhibitors of human monoamine oxidase B (MAO-B). A series of 31 new, ether-connected coumarin derivatives was synthesized via hydroxycoumarins, whose phenolic group at position 6, 7 or 8 was converted by means of the Mitsunobu reaction. The majority of the final products were produced from primary alcohols with a terminal alkyne group. The inhibitors were optimized with respect to the structure of the alkynyloxy chain and its position at the fused benzene ring as well as the residue at position 3 of the pyran-2H-one part. A hex-5-ynyloxy chain at position 7 was found to be particular advantageous. Among the 7-hex-5-ynyloxy-coumarins, the 3-methoxycarbonyl derivative 36 was characterized as a dual-acting inhibitor with IC50 values of less than 10 nM towards MAO-A and MAO-B, and the 3-(4-methoxy)phenyl derivative 44 was shown to combine strong anti-MAO-B potency (IC50 = 3.0 nM) and selectivity for MAO-B over MAO-A (selectivity >3400-fold).
Modular, gold-catalyzed approach to the synthesis of lead-like piperazine scaffolds
James, Thomas,Simpson, Iain,Grant, J. Andrew,Sridharan, Visuvanathar,Nelson, Adam
supporting information, p. 6094 - 6097 (2014/01/06)
Ring-opening of cyclic sulfamidates with propargylic sulfonamides yielded substrates for a gold-catalyzed cyclization to yield tetrahydropyrazines. Manipulation of the tetrahydropyrazines, by reduction or using multicomponent reactions, yielded piperazine scaffolds in which substitution of the carbon atoms was varied. Such scaffolds may have value in the synthesis of novel screening compounds with lead-like molecular properties.
Chemoselective hydrogenation reaction of unsaturated bonds in the presence of an o-nitrobenzenesulfonyl group
Kawanishi, Akinori,Miyamoto, Chiyako,Yabe, Yuki,Inai, Makoto,Asakawa, Tomohiro,Hamashima, Yoshitaka,Sajiki, Hironao,Kan, Toshiyuki
supporting information, p. 1306 - 1309 (2013/05/09)
Chemoselective hydrogenation of unsaturated compounds bearing an o-nitrobenzenesulfonyl (Ns)-amide moiety, affording the corresponding saturated compounds, was accomplished efficiently without loss of the nitro group by using the Pd/MS3A catalyst and a H2 balloon. Partial hydrogenation of alkynes bearing an Ns group to corresponding cis alkenes was achieved with the combination of the Pd/BN catalyst and an additive (diethylenetriamine or acetic acid).
