22731-72-2Relevant academic research and scientific papers
Mild Darzens Annulations for the Assembly of Trifluoromethylthiolated (SCF3) Aziridine and Cyclopropane Structures
Delost, Michael D.,Njardarson, Jon T.
, p. 6121 - 6125 (2021/08/16)
We report mild new annulation approaches to trisubstituted trifluoromethylthiolated (SCF3) aziridines and cyclopropanes via Darzens inspired protocols. The products of these anionic annulations, rarely studied previously, possess attractive features rendering them valuable building blocks for synthesis platforms. In this study, trisubstituted acetophenone nucleophiles bearing SCF3 and bromine substituents in their α position were shown to undergo [2 + 1] annulations with vinyl ketones and tosyl-protected imines under mild reaction conditions.
Design and synthesis of Mannich base-type derivatives containing imidazole and benzimidazole as lead compounds for drug discovery in Chagas Disease
Atherton, Richard L.,Kelly, John M.,Olmo, Francisco,Sanz-Serrano, Julen,Alcolea, Verónica,Beltran-Hortelano, Iván,Pérez-Silanes, Silvia,Rubio-Hernández, Mercedes
, (2021/07/14)
The protozoan parasite Trypanosoma cruzi is the causative agent of Chagas disease, the most important parasitic infection in Latin America. The only treatments currently available are nitro-derivative drugs that are characterised by high toxicity and limited efficacy. Therefore, there is an urgent need for more effective, less toxic therapeutic agents. We have previously identified the potential for Mannich base derivatives as novel inhibitors of this parasite. To further explore this family of compounds, we synthesised a panel of 69 new analogues, based on multi-parametric structure-activity relationships, which allowed optimization of both anti-parasitic activity, physicochemical parameters and ADME properties. Additionally, we optimized our in vitro screening approaches against all three developmental forms of the parasite, allowing us to discard the least effective and trypanostatic derivatives at an early stage. We ultimately identified derivative 3c, which demonstrated excellent trypanocidal properties, and a synergistic mode of action against trypomastigotes in combination with the reference drug benznidazole. Both its druggability and low-cost production make this derivative a promising candidate for the preclinical, in vivo assays of the Chagas disease drug-discovery pipeline.
Manganese-Catalyzed Ring-Opening Coupling Reactions of Cyclopropanols with Enones
Zhang, Yong-Hui,Zhang, Wen-Wei,Zhang, Ze-Yu,Zhao, Kai,Loh, Teck-Peng
, p. 5101 - 5105 (2019/07/03)
A manganese-catalyzed ring-opening coupling reaction of cyclopropanols with enones for the facile and efficient preparation of 1,6-diketones is described. A wide array of synthetically important 1,6-diketones bearing manifold functional groups are obtained with up to 93% yield. These reactions feature broad substrate scopes, environmentally benign conditions, inexpensive catalyst, and operational simplicity.
Structural Modification of Natural Product Ganomycin i Leading to Discovery of a α-Glucosidase and HMG-CoA Reductase Dual Inhibitor Improving Obesity and Metabolic Dysfunction in Vivo
Wang, Kai,Bao, Li,Zhou, Nan,Zhang, Jinjin,Liao, Mingfang,Zheng, Zhongyong,Wang, Yujing,Liu, Chang,Wang, Jun,Wang, Lifeng,Wang, Wenzhao,Liu, Shuangjiang,Liu, Hongwei
, p. 3609 - 3625 (2018/05/01)
It is a great challenge to develop drugs for treatment of metabolic syndrome. With ganomycin I as a leading compound, 14 meroterpene derivatives were synthesized and screened for their α-glucosidase and HMG-CoA reductase inhibitory activities. As a result, a α-glucosidase and HMG-CoA reductase dual inhibitor ((R,E)-5-(4-(tert-butyl)phenyl)-3-(4,8-dimethylnona-3,7-dien-1-yl)furan-2(5H)-one, 7d) with improved chemical stability and long-term safety was obtained. Compound 7d showed multiple and strong in vivo efficacies in reducing weight gain, lowering HbAlc level, and improving insulin resistance and lipid dysfunction in both ob/ob and diet-induced obesity (DIO) mice models. Compound 7d was also found to reduce hepatic steatosis in ob/ob model. 16S rRNA gene sequencing, SCFA, and intestinal mucosal barrier function analysis indicated that gut microbiota plays a central and causative role in mediating the multiple efficacies of 7d. Our results demonstrate that 7d is a promising drug candidate for metabolic syndrome.
Indium(III)-Catalyzed Hydration and Hydroalkoxylation of α,β-Unsaturated Ketones in Aqueous Media
Yun, Jin-Jin,Zhi, Man-Ling,Shi, Wen-Xiao,Chu, Xue-Qiang,Shen, Zhi-Liang,Loh, Teck-Peng
supporting information, p. 2632 - 2637 (2018/05/30)
The hydration of α,β-unsaturated ketones with water proceeded efficiently in the presence of In(OTf)3 (20 mol%) in aqueous media to afford synthetically versatile β-hydroxyketones in moderate to good yields with good functional group compatibility. The method also can be extended to the hydroalkoxylation of α,β-unsaturated ketones with various alcohols for the efficient synthesis of β-alkoxyketones as well as tetrahydrofuran derivatives. (Figure presented.).
Chromium(III)-Catalyzed Addition of Water and Alcohol to α,β-Unsaturated Ketones for the Synthesis of β-Hydroxyl and β-Alkoxyl Ketones in Aqueous Media
Yun, Jin-Jin,Liu, Xuan-Yu,Deng, Wei,Chu, Xue-Qiang,Shen, Zhi-Liang,Loh, Teck-Peng
, p. 10898 - 10907 (2018/09/06)
An efficient chromium(III) chloride-catalyzed Michael-type reaction of water or alcohol with α,β-unsaturated ketones is developed. A variety of α,β-unsaturated ketones effectively reacted with either water or alcohols to give the corresponding β-hydroxyl ketones or β-alkoxyl ketones in modest to high yields with excellent compatibility to various functional groups. The approach was further utilized for the preparation of synthetically useful compounds containing tetrahydrofuran skeleton.
The Pharmacological Heterogeneity of Nepenthone Analogs in Conferring Highly Selective and Potent κ-Opioid Agonistic Activities
Li, Wei,Long, Jian-Dong,Qian, Yuan-Yuan,Long, Yu,Xu, Xue-Jun,Wang, Yu-Jun,Shen, Qing,Wang, Zuo-Neng,Yang, Xi-Cheng,Xiao, Li,Sun, Hong-Peng,Xu, Yu-Long,Chen, Yi-Yi,Xie, Qiong,Wang, Yong-Hui,Shao, Li-Ming,Liu, Jing-Gen,Qiu, Zhui-Bai,Fu, Wei
, p. 766 - 776 (2017/04/26)
To develop novel analgesics with no side effects or less side effects than traditional opioids is highly demanded to treat opioid receptor mediated pain and addiction issues. Recently, κ-opioid receptor (KOR) has been established as an attractive target,
Fluorine-containing three-membered ring compound, preparation method of fluorine-containing three-membered ring compound and preparation method of fluoroalkyl sulfonium salt
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Paragraph 0172; 0173; 0174; 0175; 0180; 0181, (2016/10/08)
The invention discloses a fluorine-containing three-membered ring compound shown in the formula V-a, V-b or V-c and a preparation method thereof. The preparation method comprises that in an organic solvent, fluoroalkyl sulfur ylide shown in the formula II
Morita-Baylis-Hillman Reaction of α,β-Unsaturated Ketones with Allylic Acetates by the Combination of Transition-Metal Catalysis and Organomediation
Li, Ya-Qiong,Wang, Hai-Jun,Huang, Zhi-Zhen
, p. 4429 - 4433 (2016/07/06)
An intermolecular Morita-Baylis-Hillman (MBH) reaction of α,β-unsaturated ketones with allylic acetates under the catalysis of 10 mol % of tetrakis(triphenylphosphine)palladium(0) and mediation of tributylphosphine has been developed in the presence of acetic acid, affording the desired α-coupling products. The MBH reaction has the advantages of good tolerance to many functional groups, excellent regioselectivity and E-stereoselectivity, and moderate to good yields.
Desulfonylative Methenylation of β-Keto Sulfones
Pandey, Ganesh,Vaitla, Janakiram
supporting information, p. 4890 - 4893 (2015/10/12)
A one-step strategy for the synthesis of α-methenyl ketones from β-keto sufones is reported. Success of the methodology is elaborated for the synthesis of chromanones and isoflavanones in one-step.
