- Organophosphine-free copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur
-
A copper-catalyzed isothiocyanation of amines with sodium bromodifluoroacetate and sulfur in the absence of organophosphine has been established. This approach represents a simple and efficient one-pot synthesis of isothiocyanates, and features excellent functional group tolerance and the use of a cheap, safe and odorless sulfur source. Moreover, this process could directly provide isothiocyanate analogous bioactive molecules, thiocarbonyl-containing pesticides and facile construction of benzoxazole and benzimidazole frames.
- Feng, Wei,Zhang, Xing-Guo
-
supporting information
p. 1144 - 1147
(2019/01/28)
-
- Isothiocyanate synthesized by three components and preparation method of isothiocyanate
-
The invention discloses isothiocyanate and a preparation method thereof. The method comprises the steps that primary amine, sodium difluorobromoacetate and elemental sulfur are taken as reactants forreaction; the reaction is carried out under the action of a copper catalyst, wherein the copper catalyst is any one of cuprous chloride, copper bromide, cuprous iodide, copper chloride and copper trifluoromethanesulfonate; an alkali is also added, wherein the alkali is any one of sodium bicarbonate, potassium carbonate, cesium carbonate, potassium phosphate, DABCO and sodium tert-butoxide; the whole reaction is carried out in a solvent, wherein the solvent is acetonitrile or dimethyl sulfoxide, the reaction temperature is 80-120 DEG C, and the reaction time is 10-14 hours. The method can directly synthesize the target product, does not need to separate intermediate products and only needs stirring and heating reaction under normal pressure to obtain the target product, and the yield can beup to 87%; a waste solution is fewer during the reaction, and the method protects the environment and ensures the health of an operator; in addition, a series of isothiocyanate derivatives can be prepared, and the method has a stronger substrate universality.
- -
-
Paragraph 0041
(2019/04/26)
-
- Na2S2O8-mediated efficient synthesis of isothiocyanates from primary amines in water
-
We have developed two green, practical, and efficient procedures, including a one-pot one, to synthesize isothiocyanates from amines and carbon disulfide via desulfurization with sodium persulfate. Water is used as the solvent. Basic conditions are necessary for good chemoselectivity for isothiocyanates. Structurally diverse linear and branched alkyl amines and aryl amines are readily converted to isothiocyanates by the two procedures in satisfactory yields. Halogens, benzylic C-H bonds, methylthio, nitro, ester, alkenyl, electron-rich or -deficient (hetero)aryls, acetylenyl, and even phenolic and alcoholic hydroxyls are well tolerated. The one-pot procedure in water can also be used to realize the preparation of chiral isothiocyanates from chiral amines, and the modification of bioactive structures with free amino groups. In large-scale preparation, simple and practical purification procedures independent of column chromatography are developed.
- Fu, Zhicheng,Yuan, Wenhao,Chen, Ning,Yang, Zhanhui,Xu, Jiaxi
-
p. 4484 - 4491
(2018/10/17)
-
- Differentiating Antiproliferative and Chemopreventive Modes of Activity for Electron-Deficient Aryl Isothiocyanates against Human MCF-7 Cells
-
The consumption of Brassica vegetables provides beneficial effects through organic isothiocyanates (ITCs), products of the enzymatic hydrolysis of glucosinolate secondary metabolites. The ITC l-sulforaphane (l-SFN) is the principle agent in broccoli that demonstrates several modes of anticancer action. While the anticancer properties of ITCs like l-SFN have been extensively studied and l-SFN has been the subject of multiple human clinical trials, the scope of this work has largely been limited to those derivatives found in nature. Previous studies have demonstrated that structural changes in an ITC can lead to marked differences in a compound's potency to 1) inhibit the growth of cancer cells, and 2) alter cellular transcriptional profiles. This study describes the preparation of a library of non-natural aryl ITCs and the development of a bifurcated screening approach to evaluate the dose- and time-dependence on antiproliferative and chemopreventive properties against human MCF-7 breast cancer cells. Antiproliferative effects were evaluated using a commercial MTS cell viability assay. Chemopreventive properties were evaluated using an antioxidant response element (ARE)-promoted luciferase reporter assay. The results of this study have led to the identification of 1) several key structure–activity relationships and 2) lead ITCs for continued development.
- Anderson, Ruthellen H.,Lensing, Cody J.,Forred, Benjamin J.,Amolins, Michael W.,Aegerter, Cassandra L.,Vitiello, Peter F.,Mays, Jared R.
-
p. 1695 - 1710
(2018/08/01)
-
- Pyrazolopyrimidines: Potent Inhibitors Targeting the Capsid of Rhino- and Enteroviruses
-
There are currently no drugs available for the treatment of enterovirus (EV)-induced acute and chronic diseases such as the common cold, meningitis, encephalitis, pneumonia, and myocarditis with or without consecutive dilated cardiomyopathy. Here, we report the discovery and characterization of pyrazolopyrimidines, a well-tolerated and potent class of novel EV inhibitors. The compounds inhibit the replication of a broad spectrum of EV in vitro with IC50 values between 0.04 and 0.64 μM for viruses resistant to pleconaril, a known capsid-binding inhibitor, without affecting cytochrome P450 enzyme activity. Using virological and genetics methods, the viral capsid was identified as the target of the most promising, orally bioavailable compound 3-(4-trifluoromethylphenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine (OBR-5-340). Its prophylactic as well as therapeutic application was proved for coxsackievirus B3-induced chronic myocarditis in mice. The favorable pharmacokinetic, toxicological, and pharmacodynamics profile in mice renders OBR-5-340 a highly promising drug candidate, and the regulatory nonclinical program is ongoing. Curing the common cold! A cluster of pyrazolopyrimidines with potent broad-spectrum activity against enteroviruses was discovered. Extensive structure-property relationship analyses led to the identification of 3-(4-trifluoromethyl-phenyl)amino-6-phenylpyrazolo[3,4-d]pyrimidine-4-amine, shown to be a blocker of the viral capsid protein, as a lead compound for drug development with favorable physicochemical, pharmacokinetic, and toxicological properties.
- Makarov, Vadim A.,Braun, Heike,Richter, Martina,Riabova, Olga B.,Kirchmair, Johannes,Kazakova, Elena S.,Seidel, Nora,Wutzler, Peter,Schmidtke, Michaela
-
supporting information
p. 1629 - 1634
(2015/10/06)
-
