23786-14-3Relevant articles and documents
SUBSTITUTED PIPERAZINE DERIVATIVES USEFUL AS T CELL ACTIVATORS
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Page/Page column 103, (2021/07/02)
Disclosed are compounds of Formula (I): or a salt thereof, wherein: R1, R2, R4, R5, R6, and m are defined herein. Also disclosed are methods of using such compounds to inhibit the activity of one or both of diacylglycerol kinase alpha (DGKα) and diacylglycerol kinase zeta (DGKζ), and pharmaceutical compositions comprising such compounds. These compounds are useful in the treatment of viral infections and proliferative disorders, such as cancer.
syn-Selective Michael Reaction of α-Branched Aryl Acetaldehydes with Nitroolefins Promoted by Squaric Amino Acid Derived Bifunctional Br?nsted Bases
Campano, Teresa E.,García-Urricelqui, Ane,Mielgo, Antonia,Palomo, Claudio,de Cózar, Abel
supporting information, p. 3604 - 3612 (2021/07/26)
Here we describe a direct access to 2,2,3-trisubstituted syn γ-nitroaldehydes by addition of α-branched aryl acetaldehydes to nitroolefins promoted by a cinchona based squaric acid-derived amino acid peptide. Different α-methyl arylacetaldehydes react with β-aromatic and β-alkyl nitroolefins to afford the Michael adducts in high enantioselectivity and syn-selectivity. NMR experiments and DFT calculations predict the reaction to occur through the intermediacy of E-enolate. The interaction between the substrates and the catalyst follows Pápai's model, wherein an intramolecular H-bond interaction in the catalyst between the NH group of one of the tert-leucines and the squaramide oxygen seems to be key for discrimination of the corresponding reaction transition states.
B(C6F5)3-catalyzed O-H insertion reactions of diazoalkanes with phosphinic acids
Jiang, Jun,Zhang, Xinzhi,Zhang, Yangyang,Zhao, Jincheng
supporting information, p. 5772 - 5776 (2021/07/12)
A highly efficient base-, metal-, and oxidant-free catalytic O-H insertion reaction of diazoalkanes and phosphinic acids in the presence of B(C6F5)3has been developed. This powerful methodology provides a green approach towards the synthesis of a broad spectrum of α-phosphoryloxy carbonyl compounds with good to excellent yields (up to 99% yield). The protocol features the advantages of operational simplicity, high atom economy, practicality, easy scalability and environmental friendliness.
B(C6F5)3-Catalyzed site-selective N1-alkylation of benzotriazoles with diazoalkanes
Guo, Jing,Mandal, Dipendu,Stephan, Douglas W.,Wu, Yile,Zhao, Yunbo
supporting information, p. 7758 - 7761 (2021/08/13)
Alkylation of benzotriazoles is synthetically challenging, often leading to mixtures of N1 and N2 alkylation. Herein, metal-free catalytic site-selective N1-alkylation of benzotriazoles with diazoalkanes is described in the presence of 10 mol% of B(C6F5)3. These reactions provide N1-alkylated benzotriazoles in good to excellent yields and this protocol is successfully adapted to gram-scale syntheses as well as a derivative with antimicrobial activity.
Electrochemical oxidative: Z -selective C(sp2)-H chlorination of acrylamides
Coles, Simon J.,Hareram, Mishra Deepak,Harnedy, James,Morrill, Louis C.,Tizzard, Graham J.
supporting information, p. 12643 - 12646 (2021/12/07)
An electrochemical method for the oxidative Z-selective C(sp2)-H chlorination of acrylamides has been developed. This catalyst and organic oxidant free method is applicable across various substituted tertiary acrylamides, and provides access to a broad range of synthetically useful Z-β-chloroacrylamides in good yields (22 examples, 73% average yield). The orthogonal derivatization of the products was demonstrated through chemoselective transformations and the electrochemical process was performed on gram scale in flow.
Pd-Catalyzed Decarboxylative Olefination: Stereoselective Synthesis of Polysubstituted Butadienes and Macrocyclic P-glycoprotein Inhibitors
Chen, Xiangyang,Hao, Jiping,Houk, K. N.,Li, Yingzi,Lou, Liguang,Quan, Haitian,Song, Bichao,Wang, Lu,Xia, Yuanzhi,Xie, Peipei,Xu, Zhongliang,Yang, Weibo
supporting information, p. 9982 - 9992 (2020/06/27)
The efficient and stereoselective synthesis of polysubstituted butadienes, especially the multifunctional butadienes, represents a great challenge in organic synthesis. Herein, we wish to report a distinctive Pd(0) carbene-initiated decarboxylative olefination approach that enables the direct coupling of diazo esters with vinylethylene carbonates (VECs), vinyl oxazolidinones, or vinyl benzoxazinones to afford alcohol-, amine-, or aniline-containing 1,3-dienes in moderate to high yields and with excellent stereoselectivity. This protocol features operational simplicity, mild reaction conditions, a broad substrate scope, and gram-scalability. Notably, a structurally unique allylic Pd(II) intermediate was isolated and characterized. DFT calculation and control experiments demonstrated that a rare Pd(0) carbene intermediate could be involved in this reaction. Moreover, the polysubstituted butadienes as novel building blocks were unprecedentedly assembled into macrocycles, which efficiently inhibited the P-glycoprotein and dramatically reversed multidrug resistance in cancer cells by 190-fold.
Palladium-catalyzed intermolecular C-H silylation initiated by aminopalladation
Ji, Xiaoming,Wei, Feng,Wan, Bin,Cheng, Cang,Zhang, Yanghui
supporting information, p. 7801 - 7804 (2020/07/27)
A Pd(ii)-catalyzed intermolecular C-H silylation reaction initiated by aminopalladation has been developed. The C-H bonds were activated by an alkyl Pd(ii) species generated through aminopalladation and then disilylated with hexamethyldisilane to form disilylated indolines as the final products. The reaction provides a new method for the introduction of silyl groups into complex organic molecules.
Discovery of 2-oxy-2-phenylacetic acid substituted naphthalene sulfonamide derivatives as potent KEAP1-NRF2 protein-protein interaction inhibitors for inflammatory conditions
Lu, Meng-Chen,Shao, Hong-Li,Liu, Tian,You, Qi-Dong,Jiang, Zheng-Yu
supporting information, (2020/09/01)
Nuclear factor erythroid 2-related factor 2 (NRF2) is a pleiotropic transcription factor which regulates the constitutive and inducible transcription of a wide array of genes and confers protection against a variety of pathologies. Directly disrupting Kelch-like ECH-associated protein 1 (KEAP1)-NRF2 protein-protein interaction (PPI) has been explored as a promising strategy to activate NRF2. We reported here the first identification of a series of 2-oxy-2-phenylacetic acid substituted naphthalene sulfonamide derivatives as potent KEAP1-NRF2 inhibitors. Our efforts led to the potent small molecule KEAP1-NRF2 inhibitor, 20c, which exhibited a Kd of 24 nM to KEAP1 and an IC50 of 75 nM in disrupting KEAP1-NRF2 interaction. Subsequent biological studies provided consistent evidence across mouse macrophage cell-based and in vivo models that 20c induced NRF2 target gene expression and enhanced downstream antioxidant and anti-inflammatory activities. Our study not only demonstrated that small molecule KEAP1-NRF2 PPI inhibitors can be potential preventive and therapeutic agents for diseases and conditions involving oxidative stress and inflammation but also enriched the chemical diversity of the KEAP1-NRF2 inhibitors.
Photocatalytic Hydromethylation and Hydroalkylation of Olefins Enabled by Titanium Dioxide Mediated Decarboxylation
Zhu, Qilei,Nocera, Daniel G.
supporting information, p. 17913 - 17918 (2020/12/04)
A versatile method for the hydromethylation and hydroalkylation of alkenes at room temperature is achieved by using the photooxidative redox capacity of the valence band of anatase titanium dioxide (TiO2). Mechanistic studies support a radical-based mechanism involving the photoexcitation of TiO2 with 390 nm light in the presence of acetic acid and other carboxylic acids to generate methyl and alkyl radicals, respectively, without the need for stoichiometric base. This protocol is accepting of a broad scope of alkene and carboxylic acids, including challenging ones that produce highly reactive primary alkyl radicals and those containing functional groups that are susceptible to nucleophilic substitution such as alkyl halides. This methodology highlights the utility of using heterogeneous semiconductor photocatalysts such as TiO2 for promoting challenging organic syntheses that rely on highly reactive intermediates.
Blue Light-Promoted N?H Insertion of Carbazoles, Pyrazoles and 1,2,3-Triazoles into Aryldiazoacetates
Stivanin, Mateus L.,Fernandes, Alessandra A. G.,da Silva, Amanda F.,Okada, Celso Y.,Jurberg, Igor D.
supporting information, p. 1106 - 1111 (2020/01/25)
Blue light irradiation of aryldiazoacetates leads to the formation of free carbenes, which can react with carbazoles, pyrazoles and 1,2,3-triazoles to afford the corresponding N?H inserted products. These reactions are performed under air and at room temperature, allowing the mild preparation of a variety of motifs found in biologically relevant targets. (Figure presented.).
