136415-67-3Relevant academic research and scientific papers
N-Acylated and N-Alkylated 2-Aminobenzothiazoles Are Novel Agents That Suppress the Generation of Prostaglandin E2
Theodoropoulou, Maria A.,Psarra, Anastasia,Erhardt, Martin,Nikolaou, Aikaterini,Gerogiannopoulou, Anna-Dimitra D.,Hadjipavlou-Litina, Dimitra,Hayashi, Daiki,Dennis, Edward A.,Huwiler, Andrea,Kokotos, George
, (2022/02/09)
The quest for novel agents to regulate the generation of prostaglandin E2 (PGE2) is of high importance because this eicosanoid is a key player in inflammatory diseases. We synthesized a series of N-acylated and N-alkylated 2-aminobenzothiazoles and related heterocycles (benzoxazoles and benzimidazoles) and evaluated their ability to suppress the cytokine-stimulated generation of PGE2 in rat mesangial cells. 2-Aminobenzothiazoles, either acylated by the 3-(naphthalen-2-yl)propanoyl moiety (GK510) or N-alkylated by a chain carrying a naphthalene (GK543) or a phenyl moiety (GK562) at a distance of three carbon atoms, stand out in inhibiting PGE2 generation, with EC50 values ranging from 118 nM to 177 nM. Both GK510 and GK543 exhibit in vivo anti-inflammatory activity greater than that of indomethacin. Thus, N-acylated or N-alkylated 2-aminobenzothiazoles are novel leads for the regulation of PGE2 formation.
Synthesis of rac-ɑ-aryl propionaldehydes via branched-selective hydroformylation of terminal arylalkenes using water-soluble Rh-PNP catalyst
Gao, Peng,Ke, Miaolin,Ru, Tong,Liang, Guanfeng,Chen, Fen-Er
, p. 830 - 834 (2021/08/26)
This work detailed the preparation of a class of water-soluble PNP ligands that differed by the nature of the substitute on phenyl ring of ligands. These ligands were incorporated into water-soluble rhodium-PNP complex catalysts that were used to regioselective hydroformylation of a series of terminal arylalkenes, providing efficient access to rac-α-aryl propionaldehydes in good to excellent yield (up to 97%) and branched-regioselectivity (up to 40:1 b/l ratio). Furthermore, gram-scale and diverse synthetic transformation demonstrated synthetic application of this methodology for non-steroidal antiinflammatory drugs.
Strain-Release-Driven Friedel–Crafts Spirocyclization of Azabicyclo[1.1.0]butanes
Aggarwal, Varinder K.,Noble, Adam,Tyler, Jasper L.
supporting information, (2021/12/08)
The identification of spiro N-heterocycles as scaffolds that display structural novelty, three-dimensionality, beneficial physicochemical properties, and enable the controlled spatial disposition of substituents has led to a surge of interest in utilizing these compounds in drug discovery programs. Herein, we report the strain-release-driven Friedel–Crafts spirocyclization of azabicyclo[1.1.0]butane-tethered (hetero)aryls for the synthesis of a unique library of azetidine spiro-tetralins. The reaction was discovered to proceed through an unexpected interrupted Friedel–Crafts mechanism, generating a highly complex azabicyclo[2.1.1]hexane scaffold. This dearomatized intermediate, formed exclusively as a single diastereomer, can be subsequently converted to the Friedel–Crafts product upon electrophilic activation of the tertiary amine, or trapped as a Diels–Alder adduct in one-pot. The rapid assembly of molecular complexity demonstrated in these reactions highlights the potential of the strain-release-driven spirocyclization strategy to be utilized in the synthesis of medicinally relevant scaffolds.
Tetronics/cyclodextrin-based hydrogels as catalyst-containing media for the hydroformylation of higher olefins
Chevry,Vanbésien,Menuel,Monflier,Hapiot
, p. 114 - 123 (2017/08/14)
The rhodium-catalyzed hydroformylation of alkenes has been investigated under biphasic conditions using combinations of α-cyclodextrin (α-CD) and poloxamines (Tetronics). Thermo-responsive hydrogels containing the Rh-catalyst are formed under well-defined conditions of concentration. Hydrogels consisting of the reverse-sequential Tetronic 90R4 prove to be more effective than those containing the conventional sequential Tetronic 701. The presence of α-CD is crucial to provoke the decantation of the multiphasic system once the reaction is complete. Optimized conditions (CO/H2 pressure, Rh-precursors, phosphanes, etc.) show that the catalytic system is especially applicable to the hydroformylation of terminal alkenes. The catalytic performance remains unchanged upon recycling as the hydrogel matrix prevents the oxidation of the phosphane.
Hydroformylation of Alkenes in a Planetary Ball Mill: From Additive-Controlled Reactivity to Supramolecular Control of Regioselectivity
Cousin, Kévin,Menuel, Stéphane,Monflier, Eric,Hapiot, Frédéric
supporting information, p. 10564 - 10568 (2017/08/22)
The Rh-catalyzed hydroformylation of aromatic-substituted alkenes is performed in a planetary ball mill under CO/H2 pressure. The dispersion of the substrate molecules and the Rh-catalyst into the grinding jar is ensured by saccharides: methyl-α-d-glucopyranoside, acyclic dextrins, or cyclodextrins (CDs, cyclic oligosaccharides). The reaction affords the exclusive formation of aldehydes whatever the saccharide. Acyclic saccharides disperse the components within the solid mixture leading to high conversions of alkenes. However, they showed typical selectivity for α-aldehyde products. If CDs are the dispersing additive, the steric hindrance exerted by the CDs on the primary coordination sphere of the metal modifies the selectivity so that the β-aldehydes were also formed in non-negligible proportions. Such through-space control via hydrophobic effects over reactivity and regioselectivity reveals the potential of such solventless process for catalysis in solid state.
Chemo- and Regioselective Organo-Photoredox Catalyzed Hydroformylation of Styrenes via a Radical Pathway
Huang, He,Yu, Chenguang,Zhang, Yueteng,Zhang, Yongqiang,Mariano, Patrick S.,Wang, Wei
supporting information, p. 9799 - 9802 (2017/08/02)
An unprecedented, chemo- and regioselective, organo-photoredox catalyzed hydroformylation reaction of aryl olefins with diethoxyacetic acid as the formylation reagent is described. In contrast to traditional transition metal promoted ionic hydroformylation reactions, the new process follows a unique photoredox promoted, free radical pathway. In this process, a formyl radical equivalent, produced from diethoxacetic acid through a dye (4CzIPN) photocatalyzed, sequential oxidation-decarboxylation route, regio- and chemoselectively adds to a styrene substrate. Importantly, under the optimized reaction conditions the benzylic radical formed in this manner is reduced by SET from the anion radical of 4CzIPN to generate a benzylic anion. Finally, protonation produces the hydroformylation product. By using the new protocol, aldehydes can be generated regioselectively in up to 90% yield. A broad array of functional groups is tolerated in the process, which takes place under mild, metal-free conditions.
GLUCOSYLCERAMIDE SYNTHASE INHIBITORS FOR THE TREATMENT OF DISEASES
-
, (2015/04/15)
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and methods of using such compounds to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
Hydroformylation of olefins and reductive carbonylation of aryl halides with syngas formed ex situ from dehydrogenative decarbonylation of hexane-1,6-diol
Christensen, Stig Holden,Olsen, Esben P. K.,Rosenbaum, Jascha,Madsen, Robert
, p. 938 - 945 (2015/02/19)
A variety of primary alcohols have been investigated as convenient substrates for the ex situ delivery of carbon monoxide and molecular hydrogen in a two-chamber reactor. The gaseous mixture is liberated in one chamber by an iridium-catalysed dehydrogenative decarbonylation of the alcohol and then consumed in the other chamber in either a rhodium-catalysed hydroformylation of olefins or a palladium-catalysed reductive carbonylation of aryl halides. Hexane-1,6-diol was found to be the optimum alcohol for both reactions where moderate to excellent yields were obtained of the product aldehydes. A relatively low pressure of 1.5-2.4 bar was measured in the closed system during the two transformations.
Ligand-metal cooperating PC(sp3)P pincer complexes as catalysts in olefin hydroformylation
Musa, Sanaa,Filippov, Oleg A.,Belkova, Natalia V.,Shubina, Elena S.,Silantyev, Gleb A.,Ackermann, Lutz,Gelman, Dmitri
supporting information, p. 16906 - 16909 (2014/01/06)
Ligand-metal cooperation: A new ligand-metal cooperating catalyst for the hydroformylation of olefins is described (see scheme). The mechanism of the H2 activation and C-H bond formation of the catalyst involves an intramolecular cooperation between the structurally remote functionality and the metal center and proceeds without change of the oxidation state of the metal.
Regioselective hydroformylation of vinylarenes in aqueous media by a sol-gel entrapped rhodium catalyst
Nairoukh, Zackaria,Blum, Jochanan
scheme or table, p. 129 - 133 (2012/06/18)
Two methods for selective hydroformylation of vinylarenes in aqueous media are described. One method relies on the application of [Rh(cod)Cl]2 and a tertiary phosphane entrapped within an ionic liquid-confined silica sol-gel support. The second method utilizes the same rhodium compound, encaged within ionic-liquid-free hydrophobicized sol-gel. Both methods are best carried out at 50 °C in aqueous emulsions or microemulsions that consist of the substrate, a surfactant, a co-surfactant and >89% water. The optimal H 2/CO ratio is between 1 and 1.1. Both methods allow the reuse of the heterogenized catalyst for several runs. While the regioselectivity and the yield are hardly affected by the electronic nature of the substrates, they are significantly dependent on the reaction temperature, on the surfactant employed, and on the hydrophobicity of the support of the catalyst. Despite the use of H2 in the reactions, no transformation of the organometallic catalyst into metallic nanoparticles could be detected.
