394-35-4Relevant academic research and scientific papers
Oxidative esterification of alcohols by a single-side organically decorated Anderson-type chrome-based catalyst
Wang, Jingjing,Jiang, Feng,Tao, Chaofu,Yu, Han,Ruhlmann, Laurent,Wei, Yongge
supporting information, p. 2652 - 2657 (2021/04/21)
The direct esterification of alcohols with non-noble metal-based catalytic systems faces great challenges. Here, we report a new chrome-based catalyst stabilized by a single pentaerythritol decorated Anderson-type polyoxometalate, [N(C4H9)4]3[CrMo6O18(OH)3C{(OCH2)3CH2OH}], which can realize the efficient transformation from alcohols to esters by H2O2oxidation in good yields and high selectivity without extra organic ligands. A variety of alcohols with different functionalities including some natural products and pharmaceutical intermediates are tolerated in this system. The chrome-based catalyst can be recycled several times and still keep the original configuration and catalytic activity. We also propose a reasonable catalytic mechanism and prove the potential for industrial applications.
GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes
Wang, Congcong,Zhang, Yu-Fang,Guo, Shimeng,Zhao, Quan,Zeng, Yanping,Xie, Zhicheng,Xie, Xin,Lu, Boxun,Hu, Youhong
, p. 941 - 957 (2020/11/30)
GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as an HD target. In addition, we discovered a highly potent and specific GPR52 antagonist Comp-43 with an IC50 value of 0.63 μM by a structure-activity relationship (SAR) study. Further studies showed that Comp-43 reduces mHTT levels by targeting GPR52 and promotes survival of mouse primary striatal neurons. Moreover, in vivo study showed that Comp-43 not only reduces mHTT levels but also rescues HD-related phenotypes in HdhQ140 mice. Taken together, our study confirms that inhibition of GPR52 is a promising strategy for HD therapy, and the GPR52 antagonist Comp-43 might serve as a lead compound for further investigation.
Development of phenyltriazole thiol-based derivatives as highly potent inhibitors of DCN1-UBC12 interaction
Zhou, Wenjuan,Xu, Chenhao,Dong, Guanjun,Qiao, Hui,Yang, Jing,Liu, Hongmin,Ding, Lina,Sun, Kai,Zhao, Wen
, (2021/03/24)
Defective in cullin neddylation 1(DCN1) is a co-E3 ligase that is important for cullin neddylation. Dysregulation of DCN1 highly correlates with the development of various cancers. Herein, from the initial high-throughput screening, a novel hit compound 5a containing a phenyltriazole thiol core (IC50 value of 0.95 μM for DCN1-UBC12 interaction) was discovered. Further structure-based optimization leads to the development of SK-464 (IC50 value of 26 nM). We found that SK-464 not only directly bound to DCN1 in vitro, but also engaged cellular DCN1, suppressed the neddylation of cullin3, and hindered the migration and invasion of two DCN1-overexpressed squamous carcinoma cell lines (KYSE70 and H2170). These findings indicate that SK-464 may be a novel lead compound targeting DCN1-UBC12 interaction.
Design, synthesis, modelling studies and biological evaluation of 1,3,4-oxadiazole derivatives as potent anticancer agents targeting thymidine phosphorylase enzyme
Bajaj, Shalini,Kumar, Maushmi S.,Tinwala, Hussain,YC, Mayur
, (2021/04/12)
A series of novel 1,3,4-oxadiazole derivatives with substituted phenyl ring were designed and synthesized with an objective of discovering newer anti-cancer agents targeting thymidine phosphorylase enzyme (TP). The 1,3,4-oxadiazole derivatives were synthesized by simple and convenient methods in the lab. Chemical structure of the all the synthesized compounds were characterized by IR, 1H NMR and mass spectral methods and evaluated for cytotoxicity by MTT method against two breast cancer cell lines (MCF-7 and MDA-MB-231). Further, results of TP assay identified that 1,3,4-oxadiazole molecules displayed anti-cancer activity partially by inhibition of phosphorylation of thymidine. The TP assay identified SB8 and SB9 as potential inhibitors with anti-cancer activity against both the cell lines. The molecular docking studies recognized the orientation and binding interaction of molecule at the active site amino acid residues of TP (PDB: 1UOU). Acute toxicity studies of compound SB8 at the dose of 5000 mg/kg has identified no signs of clinical toxicity was observed. The SARs study of synthesized derivatives revealed that the substitution of phenyl ring with electron withdrawing group at ortho position showed significant TP inhibitory activity compared to para substitution. The experimental data suggests that 1,3,4-oxadiazole with substituted phenyl can be taken as a lead for the design of efficient TP inhibitors and active compounds which can be taken up for further studies.
Fluorinations of unsymmetrical diaryliodonium salts containing: Ortho -sidearms; Influence of sidearm on selectivity
Abudken, Ahmed M. H.,Hope, Eric G.,Singh, Kuldip,Stuart, Alison M.
supporting information, p. 6140 - 6146 (2020/10/30)
Activated aromatics were reacted with two different fluoroidoane reagents 1 and 2 in the presence of triflic acid to prepare only the para-substituted diaryliodonium salts. With fluoroiodane 1 the unsymmetrical diaryliodonium salts contained an ortho-propan-2-ol sidearm, whereas the alcohol sidearm was eliminated to form an ortho-styrene sidearm in the reaction with fluoroiodane 2. Only the diaryliodonium salts containing a styrene sidearm were fluorinated successfully to deliver para-fluorinated aromatics in good yields.
Cobalt Nanoparticles-Catalyzed Widely Applicable Successive C?C Bond Cleavage in Alcohols to Access Esters
Dai, Wen,Gao, Shuang,Li, Guosong,Luo, Huihui,Lv, Ying,Shang, Sensen,Wang, Lianyue
supporting information, p. 19268 - 19274 (2020/08/26)
Selective cleavage and functionalization of C?C bonds have important applications in organic synthesis and biomass utilization. However, functionalization of C?C bonds by controlled cleavage remains difficult and challenging because they are inert. Herein, we describe an unprecedented efficient protocol for the breaking of successive C?C bonds in alcohols to form esters with one or multiple carbon atoms less using heterogeneous cobalt nanoparticles as catalyst with dioxygen as the oxidant. A wide range of alcohols including inactive long-chain alkyl aryl alcohols undergo smoothly successive cleavage of adjacent ?(C?C)n? bonds to afford the corresponding esters. The catalyst was used for seven times without any decrease in activity. Characterization and control experiments disclose that cobalt nanoparticles are responsible for the successive cleavage of C?C bonds to achieve excellent catalytic activity, while the presence of Co-Nx has just the opposite effect. Preliminary mechanistic studies reveal that a tandem sequence reaction is involved in this process.
Ruthenium-catalyzed hydrogenation of CO2as a route to methyl esters for use as biofuels or fine chemicals
Li, Yong,Liu, Qingbin,Ma, Yanping,Solan, Gregory A.,Sun, Wen-Hua,Wang, Zheng,Zhang, Qiuyue,Zhao, Ziwei,Zhong, Yanxia
, p. 6766 - 6774 (2020/08/25)
A novel robust diphosphine-ruthenium(ii) complex has been developed that can efficiently catalyze both the hydrogenation of CO2 to methanol and its in situ condensation with carboxylic acids to form methyl esters; a TON of up to 3260 is achievable for the CO2 to methanol step. Both aromatic and aliphatic carboxylic acids can be transformed to their corresponding methyl esters with high conversion and selectivity (17 aliphatic and 18 aromatic examples). On the basis of a series of experiments, a mechanism has been proposed to account for the various steps involved in the catalytic pathway. More importantly, this approach provides a promising route for using CO2 as a C1 source for the production of biofuels, fine chemicals and methanol.
Facile synthesis of a highly efficient Co/Cu@NC catalyst for base-free oxidation of alcohols to esters
Jiang, Jiusheng,Li, Xiang,Du, Shengyu,Shi, Langchen,Jiang, Pingping,Zhang, Pingbo,Dong, Yuming,Leng, Yan
, p. 7780 - 7785 (2020/06/09)
The direct oxidation of alcohols to esters is an environmentally benign and cost-effective organic synthetic strategy, but it is still a great challenge to discover an economic, highly active, and long-term stable catalyst for efficient transformation of alcohols to esters under milder conditions. Herein, we developed cobalt and copper nanoparticle -co-decorated nitrogen-doped carbon catalysts (CoCu@NCn) through two steps of ball milling and calcination. It was found that CoCu@NCn could catalyze the oxidation of alcohols to esters effectively in the absence of basic additives. The catalytic activity was much higher than those of monometallic Co@NC2 and Cu@NC2 samples, and the catalyst can be conveniently recovered and quite steadily reused. Through a series of control experiments and characterizations, it is concluded that the remarkable catalytic performance of CoCu@NC2 was associated with the synergistic effect between the two metal components, the enhanced basic active sites and the active surface area.
Palladium-Catalyzed, Copper(I)-Promoted Methoxycarbonylation of Arylboronic Acids with O-Methyl S-Aryl Thiocarbonates
Cao, Ya-Fang,Li, Ling-Jun,Liu, Min,Xu, Hui,Dai, Hui-Xiong
, p. 4475 - 4481 (2020/04/10)
Here, we report O-methyl S-aryl thiocarbonates as a versatile esterification reagent for palladium-catalyzed methoxycarbonylation of arylboronic acid in the presence of copper(I) thiophene-2-carboxylate (CuTC). The reaction condition is mild, and a variety of substituents including sensitive-Cl,-Br, and free-NH2 could be tolerated. Further applications in the late-stage esterification of some pharmaceutical drugs demonstrate the broad utility of this method.
1,3-Dibromo-5,5-dimethylhydantoin as a Precatalyst for Activation of Carbonyl Functionality
?ebular, Klara,Bo?i?, Bojan ?.,Stavber, Stojan
supporting information, (2019/08/01)
Activation of carbonyl moiety is one of the most rudimentary approaches in organic synthesis and is crucial for a plethora of industrial-scale condensation reactions. In esterification and aldol condensation, which represent two of the most important reactions, the susceptibility of the carbonyl group to nucleophile attack allows the construction of a variety of useful organic compounds. In this context, there is a constant need for development of and improvement in the methods for addition-elimination reactions via activation of carbonyl functionality. In this paper, an advanced methodology for the direct esterification of carboxylic acids and alcohols, and for aldol condensation of aldehydes using widely available, inexpensive, and metal-free 1,3-dibromo-5,5-dimethylhydantoin under neat reaction conditions is reported. The method is air- and moisture-tolerant, allowing simple synthetic and isolation procedures for both reactions presented in this paper. The reaction pathway for esterification is proposed and a scale-up of certain industrially important derivatives is performed.
