946-39-4Relevant articles and documents
New tranylcypromine derivatives containing sulfonamide motif as potent LSD1 inhibitors to target acute myeloid leukemia: Design, synthesis and biological evaluation
Cen, Meifeng,Du, Yongliang,Ganesan, A.,Huang, Peng,Liang, Liyun,Luo, Bingling,Meng, Ning,Wang, Haiwen,Wen, Shijun
, (2020)
Lysine-specific demethylase 1 (LSD1) is frequently elevated in acute myeloid leukemia (AML) and often leads to tumorigenesis. In recent years, numerous LSD1 inhibitors based on tranylcypromine (TCP) scaffolding have reached clinical trials. Most TCP derivatives were modified at the amino site of cyclopropane motif. Herein, we for the first time introduced a sulfonamide group in TCP benzene ring of series a compounds and performed a systematical study on structure and activity relationships by varying sulfonamide groups. The introduction of sulfonamide significantly increased the targeting capacity of TCP against LSD1. Moreover, we discovered that the Boc attached LSD1 inhibitors (labelled as series b compounds) substantially improved their anti-proliferation capacity towards AML cells. The intracellular thermal shift and LC-MS/MS results implied that Boc enhanced the drug lipophilicity and might be removed under the cancerous acidic environment to release the real pharmacophore, evidenced by the fact that a structurally similar but acidic inert pivaloyl to replace Boc dramatically dropped the cellular anti-proliferation effect. Finally, a benzyl group installed at the amino site to appropriately increase lipophilicity led to trans-4-(2-(benzylamino)-cyclopropyl)-N,N-diethylbenzenesulfonamide a10 that showed better anti-proliferation activity in AML cells and enzymatic inhibition against LSD1. Taken together, our work offers a novel TCP-based structure and provides a prodrug strategy for the discovery of potent LSD1 inhibitors by having appropriate lipophilicity.
Electrochemical Ring-Opening Dicarboxylation of Strained Carbon-Carbon Single Bonds with CO2: Facile Synthesis of Diacids and Derivatization into Polyesters
Liao, Li-Li,Wang, Zhe-Hao,Cao, Ke-Gong,Sun, Guo-Quan,Zhang, Wei,Ran, Chuan-Kun,Li, Yiwen,Chen, Li,Cao, Guang-Mei,Yu, Da-Gang
supporting information, p. 2062 - 2068 (2022/02/10)
Diacids are important monomers in the polymer industry to construct valuable materials. Dicarboxylation of unsaturated bonds, such as alkenes and alkynes, with CO2 has been demonstrated as a promising synthetic method. However, dicarboxylation of C-C single bonds with CO2 has rarely been investigated. Herein we report a novel electrochemical ring-opening dicarboxylation of C-C single bonds in strained rings with CO2. Structurally diverse glutaric acid and adipic acid derivatives were synthesized from substituted cyclopropanes and cyclobutanes in moderate to high yields. In contrast to oxidative ring openings, this is also the first realization of an electroreductive ring-opening reaction of strained rings, including commercialized ones. Control experiments suggested that radical anions and carbanions might be the key intermediates in this reaction. Moreover, this process features high step and atom economy, mild reaction conditions (1 atm, room temperature), good chemoselectivity and functional group tolerance, low electrolyte concentration, and easy derivatization of the products. Furthermore, we conducted polymerization of the corresponding diesters with diols to obtain a potential UV-shielding material with a self-healing function and a fluorine-containing polyester, whose performance tests showed promising applications.
Synthesis, structure and reactivity of iridium complexes containing a bis-cyclometalated tridentate C^N^C ligand
Cheng, Shun-Cheung,Cheung, Wai-Man,Chong, Man-Chun,Ko, Chi-Chiu,Leung, Wa-Hung,Sung, Herman H.-Y.,Williams, Ian D.
, p. 8512 - 8523 (2021/06/28)
In an effort to synthesize cyclometalated iridium complexes containing a tridentate C^N^C ligand, transmetallation of [Hg(HC^N^C)Cl] (1) (H2C^N^C = 2,6-bis(4-tert-butylphenyl)pyridine) with various organoiridium starting materials has been studied. The treatment of1with [Ir(cod)Cl]2(cod = 1,5-cyclooctadiene) in acetonitrile at room temperature afforded a hexanuclear Ir4Hg2complex, [Cl(κ2C,N-HC^N^C)(cod)IrHgIr(cod)Cl2]2(2), which features Ir-Hg-Ir and Ir-Cl-Ir bridges. Refluxing2with sodium acetate in tetrahydrofuran (thf) resulted in cyclometalation of the bidentate HC^N^C ligand and formation of trinuclear [(C^N^C)(cod)IrHgIr(cod)Cl2] (3). On the other hand, refluxing [Ir(cod)Cl]2with1and sodium acetate in thf yielded [Ir(C^N^C)(cod)(HgCl)] (4). Chlorination of4with PhICl2gave [Ir(C^N^C)(cod)Cl]·HgCl2(5·HgCl2) that reacted with tricyclohexylphosphine to yield Hg-free [Ir(C^N^C)(cod)Cl] (5). Chloride abstraction of5with silver(i) triflate (AgOTf) gave [Ir(C^N^C)(cod)(H2O)](OTf) (6) that can catalyze the cyclopropanation of styrene with ethyl diazoacetate. Reaction of1and [Ir(CO)2Cl(py)] (py = pyridine) with sodium acetate in refluxing thf afforded [Ir(C^N^C)(HgCl)(py)(CO)] (7), in which the carbonyl ligand is coplanar with the C^N^C ligand. On the other hand, refluxing1with (PPh4)[Ir(CO)2Cl2] and sodium acetate in acetonitrile gave [Ir(C^N^C)(κ2C,N-HC^N^C)(CO)] (8), the carbonyl ligand of which istransto the pyridyl ring of the bidentate HC^N^C ligand. Upon irradiation with UV light8in thf was isomerized to8′, in which the carbonyl istransto a phenyl group of the bidentate HC^N^C ligand. The isomer pair8and8′exhibited emission at 548 and 514 nm in EtOH/MeOH at 77 K with lifetime of 84.0 and 64.6 μs, respectively. Protonation of8withp-toluenesulfonic acid (TsOH) afforded the bis(bidentate) tosylate complex [Ir(κ2C,N-HC^N^C)2(CO)(OTs)] (9) that could be reconverted to8upon treatment with sodium acetate. The electrochemistry of the Ir(C^N^C) complexes has been studied using cyclic voltammetry. Reaction of [Ir(PPh3)3Cl] with1and sodium acetate in refluxing thf led to isolation of the previously reported compound [Ir(κ2P,C-C6H4PPh2)2(PPh3)Cl] (10). The crystal structures of2-5,8,8′,9and10have been determined.
Catalytic cyclopropanation, antimicrobial, and DFT properties of some chelated transition metal(II) complexes
Ababneh, Taher S.,Al-Dawood, Lina A.,Al-Momani, Waleed M.,Hijazi, Ahmed K.,Taha, Ziyad A.
, (2020/12/25)
Transition Metal (II) complexes of general formula [MII(NH2C2H4NH2)3][B(C6F5)4]2 (1-6), where (M= Mn, Fe, Co, Ni, Cu, Zn) have been synthesized and characterized in the solid state and in solution using elemental, thermogravimetric analysis, EPR, 11B-NMR and IR spectroscopy. All complexes were used as catalysts for the cyclopropanation reaction with a variety of olefins. Excellent yields up to 93% were obtained using complex 5. All prepared complexes were used as anti-bacterial agents against different types of bacteria (Gram-negative and Gram-positive), and as anti-fungal agents. Complex 6 showed the highest activity with MIC value of 8 μg/mL against Staphylococcus aureus (Gram-positive bacteria), and of 16 μg/mL against candida albicans. To get more insights into their structural features, molecular geometries of all prepared complexes were fully optimized using density functional theory calculations at the M06-2X/6-311+G** level of theory.
