55369-69-2Relevant academic research and scientific papers
Chemoselectivity for Alkene Cleavage by Palladium-Catalyzed Intramolecular Diazo Group Transfer from Azide to Alkene
Frost, Grant B.,Mittelstaedt, Michaela N.,Douglas, Christopher J.
supporting information, p. 1727 - 1732 (2019/01/09)
Alkenes can be cleaved by means of the (3+2) cycloaddition and subsequent cycloreversion of 1,3-dipoles, classically ozone (O3), but the azide (R?N3) variant is rare. Chemoselectivity for these azide to alkene diazo group transfers (DGT) is typically disfavored, thus limiting their synthetic utility. Herein, this work discloses a palladium-catalyzed intramolecular azide to alkene DGT, which grants chemoselectivity over competing aziridination. The data support a catalytic cycloreversion mechanism distinct from other known metal-catalyzed azide/alkene reactions: nitrenoid/metalloradical and (3+2) cycloadditions. Kinetics experiments reveal an unusual mechanistic profile in which the catalyst is not operative during the rate-controlling step, rather, it is active during the product-determining step. Catalytic DGT was used to synthesize N-heterocyclic quinazolinones, a medicinally relevant structural core. We also report on the competing aziridination and subsequent ring expansion to another N-heterocyclic core structure of interest, benzodiazepinones.
Design, synthesis and biological activity of selective hCAs inhibitors based on 2-(benzylsulfinyl)benzoic acid scaffold
Rotondi, Giulia,Guglielmi, Paolo,Carradori, Simone,Secci, Daniela,De Monte, Celeste,De Filippis, Barbara,Maccallini, Cristina,Amoroso, Rosa,Cirilli, Roberto,Akdemir, Atilla,Angeli, Andrea,Supuran, Claudiu T.
, p. 1400 - 1413 (2019/08/26)
A large library of derivatives based on the scaffold of 2-(benzylsulfinyl)benzoic acid were synthesised and tested as atypical inhibitors against four different isoforms of human carbonic anhydrase (hCA I, II, IX and XII, EC 4.2.1.1). The exploration of the chemical space around the main functional groups led to the discovery of selective hCA IX inhibitors in the micromolar/nanomolar range, thus establishing robust structure-activity relationships within this versatile scaffold. HPLC separation of some selected chiral compounds and biological evaluation of the corresponding enantiomers was performed along with molecular modelling studies on the most active derivatives.
Para-Selective C-H Olefination of Aniline Derivatives via Pd/S,O-Ligand Catalysis
Naksomboon, Kananat,Poater, Jordi,Bickelhaupt, F. Matthias,Fernández-Ibá?ez, M. ángeles
supporting information, p. 6719 - 6725 (2019/05/06)
Herein we report a highly para-selective C-H olefination of aniline derivatives by a Pd/S,O-ligand-based catalyst. The reaction proceeds under mild reaction conditions with high efficiency and broad substrate scope, including mono-, di-, and trisubstituted tertiary, secondary, and primary anilines. The S,O-ligand is responsible for the dramatic improvements in substrate scope and the high para-selectivity observed. This methodology is operationally simple, scalable, and can be performed under aerobic conditions.
Rapid and reversible hydrazone bioconjugation in cells without the use of extraneous catalysts
Nisal, Rahul,Jose, Gregor,Shanbhag, Chitra,Kalia, Jeet
, p. 4304 - 4310 (2018/06/22)
The amenability of hydrazone linkages to disassemble via either hydrolysis in mildly acidic aqueous solutions or transimination upon treatment with amine nucleophiles renders them extremely attractive for applications in chemical biology, drug delivery and materials science. Unfortunately, however, the use of hydrazones is hampered by the extremely slow intrinsic rates of their formation from their hydrazine and carbonyl precursors. Consequently, hydrazone formation is typically performed in the presence of a large excess of cytotoxic aniline-based nucleophilic catalysts, rendering hydrazones unsuitable for biological applications that entail their formation in cells. Herein, we report a hydrazine scaffold - o-amino benzyl hydrazine - that rapidly forms hydrazones via intramolecular nucleophilic catalysis, thereby obviating the use of extraneous catalysts. We demonstrate the use of this scaffold for rapid and reversible peptide and protein hydrazone bioconjugation and also for reversible fluorescent labeling of sialylated glycoproteins and choline lipids in mammalian cells.
Electrocatalytic C-H/N-H Coupling of 2′-Aminoacetophenones for the Synthesis of Isatins
Qian, Peng,Su, Ji-Hu,Wang, Yukang,Bi, Meixiang,Zha, Zhenggen,Wang, Zhiyong
, p. 6434 - 6440 (2017/06/23)
2′-Aminoacetophenones undergo a C(sp3)-H oxidation followed by intramolecular C-N bond formation by virtue of a simple electrochemical oxidation in the presence of n-Bu4NI, providing various isatins with moderate to good yields. The reaction intermediates were detected, and a radical-based pathway was proposed.
A General and Direct Reductive Amination of Aldehydes and Ketones with Electron-Deficient Anilines
Pletz, Jakob,Berg, Bernhard,Breinbauer, Rolf
supporting information, p. 1301 - 1317 (2016/05/02)
In our ongoing efforts in preparing tool compounds for investigating and controlling the biosynthesis of phenazines, we recognized the limitations of existing protocols for C-N bond formation of electron-deficient anilines when using reductive amination. After extensive optimization, we have established three robust and scalable protocols for the reductive amination of ketones with electron-deficient anilines, by using either BH3·THF/AcOH/CH2Cl2 (method A), with reaction times of several hours, or the more powerful combinations BH3·THF/TMSCl/DMF (method B) and NaBH4/TMSCl/DMF (method C), which give full conversions for most substrates within 10 to 25 minutes. The scope and limitations of these reactions have been defined for 12 anilines and 14 ketones.
Sunlight-Driven Forging of Amide/Ester Bonds from Three Independent Components: An Approach to Carbamates
Zhao, Yating,Huang, Binbin,Yang, Chao,Chen, Qingqing,Xia, Wujiong
supporting information, p. 5572 - 5575 (2016/11/17)
A photoredox catalytic route to carbamates enabled by visible irradiation (or simply sunlight) has been developed. This process leads to a novel approach to the construction of heterocyclic rings wherein the amide or ester motifs of carbamates were assembled from three isolated components. Large-scale experiments were realized by employing continuous flow techniques, and reuse of photocatalyst demonstrated the green and sustainable aspects of this method.
Investigation into the stability and reactivity of the pentacyclic alkaloid dehydroevodiamine and the benz-analog thereof
Wehle, Sarah,Espargaró, Alba,Sabaté, Raimon,Decker, Michael
, p. 2535 - 2543 (2016/04/26)
Limited synthetic approaches to obtain the biologically active alkaloid dehydroevodiamine (DHED) are known to date. Undesired demethylation in the most widely applied route was found to be a hampering side reaction for the benz-DHED derivative leading to a quinazolinone, which represents a benz-rutaecarpine derivative. For rutaecarpine, a related plant alkaloid, many different synthetic approaches have been described. Alternative reaction procedures to obtain DHED such as methylation of rutaecarpine and oxidation of evodiamine were investigated to make DHED more easily accessible and the latter method proved to be the most successful one. Furthermore, the remarkable equilibrium between the ring closed quinazolinium and the ring open form of the compounds was systematically investigated by UV-vis measurements. The ring open form and the quinazolinium salt, form the same species when incubated in buffer solution for 24 h. A better soluble form, i.e., 'hydroxyevodiamine', seems to represent the biologically active form that has not yet been described.
Reinvestigating Raney nickel mediated selective alkylation of amines with alcohols via hydrogen autotransfer methodology
Mehta, Astha,Thaker,Londhe,Nandan, Santosh R.
, p. 241 - 251 (2014/05/20)
An efficient, cost-effective use of Raney nickel (R-Ni) a widely used industrial catalyst for N-alkylation using alcohols is highlighted here. The work describes the scope and capability of R-Ni in hydrogen autotransfer reactions enabling its widespread use in the Chemical and Pharmaceutical industry. R-Ni of W4, T4, and W7 grades were prepared and evaluated for alkylation of amines. The best activity and selectivity for mono alkylation of amines were obtained using W4 R-Ni at 1:4 moles of amine to alcohol in xylene at reflux. T4 R-Ni also showed ability to form stable imines. The prepared R-Ni was also recycled and reused for N-alkylation reaction. The optimized methodology was applied for synthesis of Active Pharmaceutical ingredients Piribedil and Mepyramine. The simplicity and wide substrate scope makes this method a preferred Hydrogen Auto-transfer protocol for the alkylation of amines.
Synthesis and anti-parasitic activity of a novel quinolinone-chalcone series
Roussaki, Marina,Hall, Belinda,Lima, Sofia Costa,Da Silva, Anabela Cordeiro,Wilkinson, Shane,Detsi, Anastasia
supporting information, p. 6436 - 6441 (2013/11/19)
A series of novel quinolinone-chalcone hybrids and analogues were designed, synthesized and their biological activity against the mammalian stages of Trypanosoma brucei and Leishmania infantum evaluated. Promising molecular scaffolds with significant microbicidal activity and low cytotoxicity were identified. Quinolinone-chalcone 10 exhibited anti-parasitic properties against both organisms, being the most potent anti-L. infantum agent of the entire series (IC50 value of 1.3 ± 0.1 μM). Compounds 4 and 11 showed potency toward the intracellular, amastigote stage of L. infantum (IC50 values of 2.1 ± 0.6 and 3.1 ± 1.05 μM, respectively). Promising trypanocidal compounds include 5 and 10 (IC 50 values of 2.6 ± 0.1 and 3.3 ± 0.1 μM, respectively) as well as 6 and 9 (both having IC50 values of 5 μM). Chemical modifications on the quinolinone-chalcone scaffold were performed on selected compounds in order to investigate the influence of these structural features on antiparasitic activity.
