153850-83-0Relevant articles and documents
Electrochemical Decarboxylative Cyclization of α-Amino-Oxy Acids to Access Phenanthridine Derivatives
Zhan, Yanling,Dai, Changhui,Zhu, Zitong,Liu, Ping,Sun, Peipei
supporting information, (2022/02/07)
Phenanthridines are a class of useful heterocycles in the field of drug development. In this work, a method via electrochemical decarboxylative cyclization of α-amino-oxy acids to access phenanthridine derivatives was developed. This reaction proceeded th
Gold Catalysts Can Generate Nitrone Intermediates from a Nitrosoarene/Alkene Mixture, Enabling Two Distinct Catalytic Reactions: A Nitroso-Activated Cycloheptatriene/Benzylidene Rearrangement
Cheng, Mu-Jeng,Kardile, Rahul Dadabhau,Kuo, Tung-Chun,Liu, Rai-Shung,More, Sayaji Arjun
, p. 5506 - 5511 (2021/07/31)
Gold-catalyzed reactions of cycloheptatrienes with nitrosoarenes yield nitrone derivatives efficiently. This reaction sequence enables us to develop gold-catalyzed aerobic oxidations of cycloheptatrienes to afford benzaldehyde derivatives using CuCl and nitrosoarenes as co-catalysts (10-30 mol %). Our density functional theory calculations support a novel nitroso-activated rearrangement, tropylium → benzylidene. With the same nitrosoarenes, we developed their gold-catalyzed [2 + 2 + 1]-annulations between nitrosobenzene and two enol ethers to yield 5-alkoxyisoxazolidines using 1,4-cyclohexadienes as hydrogen donors.
Structure-Guided Development of Potent Benzoylurea Inhibitors of BCL-XLand BCL-2
Roy, Michael J.,Vom, Amelia,Okamoto, Toru,Smith, Brian J.,Birkinshaw, Richard W.,Yang, Hong,Abdo, Houda,White, Christine. A.,Segal, David,Huang, David C. S.,Baell, Jonathan B.,Colman, Peter M.,Czabotar, Peter E.,Lessene, Guillaume
, p. 5447 - 5469 (2021/05/31)
The BCL-2 family of proteins (including the prosurvival proteins BCL-2, BCL-XL, and MCL-1) is an important target for the development of novel anticancer therapeutics. Despite the challenges of targeting protein-protein interaction (PPI) interfaces with small molecules, a number of inhibitors (called BH3 mimetics) have entered the clinic and the BCL-2 inhibitor, ABT-199/venetoclax, is already proving transformative. For BCL-XL, new validated chemical series are desirable. Here, we outline the crystallography-guided development of a structurally distinct series of BCL-XL/BCL-2 inhibitors based on a benzoylurea scaffold, originally proposed as α-helix mimetics. We describe structure-guided exploration of a cryptic "p5"pocket identified in BCL-XL. This work yields novel inhibitors with submicromolar binding, with marked selectivity toward BCL-XL. Extension into the hydrophobic p2 pocket yielded the most potent inhibitor in the series, binding strongly to BCL-XL and BCL-2 (nanomolar-range half-maximal inhibitory concentration (IC50)) and displaying mechanism-based killing in cells engineered to depend on BCL-XL for survival.
Metal-Free Electrochemical Coupling of Vinyl Azides: Synthesis of Phenanthridines and β-Ketosulfones
Chen, Qianjin,Kong, Xianqiang,Li, Guodong,Liang, Qi,Lin, Long,Xu, Bo,Yu, Ke
supporting information, p. 6135 - 6145 (2020/10/06)
We reported an efficient and environmentally benign electrochemical synthesis of phenanthridines by oxidative coupling of vinyl azides with sodium azide or benzenesulfonyl hydrazides, for the first time. The reaction conditions are mild, and no additional metal-catalyst or exogenous oxidants are needed. The protocol has broad substrate scope and high functional group tolerance. Furthermore, this green electrochemical procedure can be readily extended to the synthesis of β-ketosulfones. Gram scale reactions further demonstrate the practicability.
Interplay between n→π? Interactions and Dynamic Covalent Bonds: Quantification and Modulation by Solvent Effects
Zheng, Hao,Ye, Hebo,Yu, Xiaoxia,You, Lei
supporting information, p. 8825 - 8833 (2019/06/13)
Orbital donor-acceptor interactions play critical roles throughout chemistry, and hence, their regulation and functionalization are of great significance. Herein we demonstrate for the first time the investigation of n→π? interactions through the strategy of dynamic covalent chemistry (DCC), and we further showcase its use in the stabilization of imine. The n→π? interaction between donor X and acceptor aldehyde/imine within 2-X-2′-formylbiphenyl derivatives was found to significantly influence the thermodynamics of imine exchange. The orbital interaction was then quantified through imine exchange, the equilibrium of which was successfully correlated with the difference in natural bond orbital stabilization energy of n→π? interactions of aldehyde and its imine. Moreover, the examination of solvent effects provided insights into the distinct feature of the modulation of n→π? interaction with aprotic and protic solvents. The n→π? interaction involving imine was enhanced in protic solvents due to hydrogen bonding with the solvent. This finding further enabled the stabilization of imine in purely aqueous solution. The strategies and results reported should find application in many fields, including molecular recognition, biological labeling, and asymmetric catalysis.
Chromium-Catalyzed, Regioselective Cross-Coupling of C-O Bonds by Using Organic Bromides as Reactants
Tang, Jinghua,Luo, Meiming,Zeng, Xiaoming
, p. 2577 - 2580 (2017/09/28)
We report a chromium-catalyzed cross-coupling of C-O bonds with widely accessible organic bromides as reactants for the preparation of ortho -arylated or -alkylated aromatic aldehydes at room temperature. The use of metallic magnesium is essential for the reaction to occur, giving it an advantage over previous reactions involving Grignard reagents that have to be prepared separately from organic halides before the coupling.
Low-Valent, High-Spin Chromium-Catalyzed Cleavage of Aromatic Carbon-Nitrogen Bonds at Room Temperature: A Combined Experimental and Theoretical Study
Cong, Xuefeng,Fan, Fei,Ma, Pengchen,Luo, Meiming,Chen, Hui,Zeng, Xiaoming
, p. 15182 - 15190 (2017/10/31)
The cleavage of aromatic carbon-nitrogen bonds catalyzed by transition metals is of high synthetic interest because such bonds are common in organic chemistry. However, few metal catalysts can be used to selectively break C(aryl)-N bonds in electronically neutral molecules. We report here the first low-valent, high-spin chromium-catalyzed cleavage of C(aryl)-N bonds in electronically neutral aniline derivatives at room temperature. By using simple and inexpensive chromium(II) chloride as precatalyst, accompanied by an imino auxiliary, the selective arylative and alkylative C-C coupling of C(aryl)-N bonds can be achieved. Crossover experiments indicate that a low-valent chromium species, formed in situ by reduction of CrCl2 with Grignard reagent, is responsible for the catalytic cleavage of C(aryl)-N bonds. DFT calculations show that facile insertion of the C(aryl)-N bond by chromium(0) can take place in a high-spin quintet (S = 2) ground state, whereas the lower-spin singlet (S = 0) and triplet (S = 1) states are inaccessible in energy. It was found that both donation of the sole paired d electrons in the d6 shell of high-spin chromium(0) to the antibonding orbital of the C(aryl)-N bond and the nitrogen ligating interaction to the metal center with its lone pair play important roles in the cleavage of the C(aryl)-N bond by the zerovalent chromium species.
ACYLSULFONAMIDE DERIVATIVES FOR TREATING SENESCENCE-ASSOCIATED DISEASES AND DISORDERS
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Paragraph 0284; 0286, (2017/07/14)
Compounds represented by Formula (I) and (II) and salts thereof are described herein. The compounds or salts of Formula (I) and (II) may be used to treat senescence-associated diseases and disorders.
Synthesis of dibenzopyranones and pyrazolobenzopyranones through copper(0)/Selectfluor system-catalyzed double C[sbnd]H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes
Zhang, Jian,Shi, Dongdong,Zhang, Haifeng,Xu, Zheng,Bao, Hanyang,Jin, Hongwei,Liu, Yunkui
, p. 154 - 163 (2016/12/23)
A mild and efficient protocol for the synthesis of dibenzopyranones and pyrazolobenzopyranones was developed involving a copper(0)/Selectfluor system-catalyzed double C[sbnd]H activation/oxygen insertion of 2-arylbenzaldehydes and 5-arylpyrazole-4-carbaldehydes. Preliminary mechanistic studies suggest that both water and dioxygen act as the oxygen source in the formation of pyranone scaffolds.
Gold-Catalyzed Oxidation Terminal Alkyne: An Approach to Synthesize Substituted Dihydronaphthalen-2(1H)-ones and Phenanthrenols
Ling, Hui-Bo,Chen, Zi-Sheng,Yang, Fang,Xu, Bin,Gao, Jin-Ming,Ji, Kegong
, p. 7070 - 7076 (2017/07/15)
A facile gold-catalyzed oxidation terminal alkynes to synthesize substituted dihydronaphthalen-2(1H)-ones 3 and phenanthrenols 5 was realized. Various useful structures and drug precursors were generated in up to 99% yield under mild condition and low catalyst loading.
