69468-42-4Relevant academic research and scientific papers
Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections
Xu, Hang,Yan, Zhong-zuo,Guo, Meng-bi,An, Ran,Wang, Xin,Zhang, Rui,Mou, Yan-hua,Hou, Zhuang,Guo, Chun
, (2021/03/16)
A series of selenium-containing miconazole derivatives were identified as potent antifungal drugs in our previous study. Representative compound A03 (MIC = 0.01 μg/mL against C.alb. 5314) proved efficacious in inhibiting the growth of fungal pathogens. However, further study showed lead compound A03 exhibited potential hemolysis, significant cytotoxic effect and unfavorable metabolic stability and was therefore modified to overcome these drawbacks. In this article, the further optimization of selenium-containing miconazole derivatives resulted in the discovery of similarly potent compound B17 (MIC = 0.02 μg/mL against C.alb. 5314), exhibiting a superior pharmacological profile with decreased rate of metabolism, cytotoxic effect and hemolysis. Furthermore, compound B17 showed fungicidal activity against Candida albicans and significant effects on the treatment of resistant Candida albicans infections. Meanwhile, compound B17 not only could reduce the ergosterol biosynthesis pathway by inhibiting CYP51, but also inhibited biofilm formation. More importantly, compound B17 also shows promising in vivo efficacy after intraperitoneal injection and the PK study of compound B17 was evaluated. In addition, molecular docking studies provide a model for the interaction between the compound B17 and the CYP51 protein. Overall, we believe that these selenium-containing miconazole compounds can be further developed for the potential treatment of fungal infections.
Synthetic method of diselenide compound
-
Paragraph 0047-0063, (2021/03/13)
The invention relates to a synthetic method of a diselenide compound, which comprises the following steps: putting arylboronic acid or derivatives thereof, elemental selenium, trimethylsilyl cyanide and an organic solvent into a reaction container to obtain a mixed solution, heating the mixed solution to 110-140 DEG C, stirring and reacting at the temperature for 18-30 hours to obtain a reaction solution, and carrying out aftertreatment to obtain a diselenide compound, wherein the ratio of the arylboronic acid or the derivative of the arylboronic acid to the elemental selenium to the trimethylsilyl cyanide is (6-10): (9-11): 1, wherein the dosage of the organic solvent is 4-6ml/mmol based on the molar weight of the arylboronic acid or the derivative thereof. The method has the following beneficial effects: 1, elemental selenium is adopted to replace a metal catalyst, metal is not needed for catalytic reaction, and the product is relatively environment-friendly; 2, the reaction conditions are mild, and the functional group tolerance is good; 3, a non-aryl phenol compound is used, so that the method is relatively environment-friendly; and 4, the yield is high.
Highly selective radical isothiocyano-chalcogenization of alkenes with NH4SCN in water
He, Ze,Kang, Xiaokang,Xu, Chao,Zeng, Qingle
supporting information, p. 7544 - 7548 (2021/10/12)
In the presence of catalytic amounts of molecular iodine and stoichiometric potassium persulfate, a green, highly chemoselective, regioselective and cis-selective radical isothiocyano-chalcogenization of alkenes with NH4SCN in water is disclosed. This three component reaction features high selectivities, an environmentally benign process, mild conditions, high yields, excellent functional-group tolerance, and broad substrate scope. The resulting products can be further transformed into other molecules with structural similarities of these compounds to bioactive analogs.
FeCl3-catalyzed three-component aryl-selenylation of alkenes
Xu, Chao,He, Ze,Yang, Hongqin,Chen, Hongyi,Zeng, Qingle
, (2021/06/07)
FeCl3-catalyzed three-component aryl-selenylation of alkenes with good to excellent yields has been disclosed. This method is characterized by synthesis of complicated products in a single-step reaction, simple operation and readily available commercially reagents. Finally, a reasonable mechanism of FeCl3-catalyzed aryl-selenylation is proposed.
Visible-light-driven radical 1,3-addition of selenosulfonates to vinyldiazo compounds
Li, Weiyu,Zhou, Lei
supporting information, p. 6652 - 6658 (2021/09/10)
Herein, we report a visible-light-driven radical 1,3-selenosulfonylation of vinyldiazo compounds with selenosulfonates, providing various γ-seleno allylic sulfones in good yields. This photochemical reaction was carried out at room temperature in an open flask using ethyl acetate as the solvent without any photocatalysts or additives. The control experiments corroborated that the 1,3-addition proceeded via a radical-chain propagation process. The synthetic applications of the resulting products were demonstrated by deselenization, reduction, bromination and allylation.
Rhodium-Catalyzed Enantioselective Hydroselenation of Heterobicyclic Alkenes
Li, Sifeng,Yang, Qingjing,Bian, Zhaoxiang,Wang, Jun
supporting information, p. 2781 - 2785 (2020/03/30)
A highly efficient Rh(I)/(S)-xyl-Binap catalytic system is developed for the asymmetric hydroselenation of various nonpolar olefins with diselenides. Under these mild reaction conditions, a wide range of heterobicyclic alkenes give selenol-incorporated adducts in excellent enantioselectivities (up to 97%) along with high yields (up to 96%) by overcoming self-promoted racemic hydroselenation. The strategy is also applied for kinetic resolution of unsymmetric oxabenzonorbornadiene.
Transition metal-free coupling reactions of benzylic trimethylammonium salts with di(hetero)aryl disulfides and diselenides
Li, Fuhai,Wang, Dan,Chen, Hongyi,He, Ze,Zhou, Lihong,Zeng, Qingle
supporting information, p. 13029 - 13032 (2020/11/07)
A new protocol was developed to synthesize (enantioenriched) thioethers and selenoethers from (chiral) benzylic trimethylammonium salts and di(hetero)aryl disulfides or diselenides. These syntheses were promoted by the presence of weak base and did not require the use of any transition metal, and resulted in the target products with good to excellent yields (72-94%). Using quaternary ammonium salts synthesized from enantiomerically enriched amines led to highly enantiopure benzylic thioethers and selenoethers (94-99% ee) with configurations reversed from those of their enantioenriched quaternary ammonium salts. This journal is
In situ synthesis of CuO nanoparticles over functionalized mesoporous silica and their application in catalytic syntheses of symmetrical diselenides
Das, Trisha,Chatterjee, Rana,Majee, Adinath,Uyama, Hiroshi,Morgan, David,Nandi, Mahasweta
, p. 17874 - 17886 (2019/12/24)
A versatile and novel catalyst, CuO nanoparticles immobilized over functionalized mesoporous silica (nCuO-FMS), has been synthesized over an organically modified mesoporous silica framework following a facile synthetic route. The surface of the silica support (SBA-15) is first grafted with the 3-aminopropyl silane group and then further functionalized with tris(4-formylphenyl)amine. The reaction is performed in such a way that a few -CHO groups remain free for further functionalization. Finally, the CuO nanoparticles immobilized on mesoporous silica are obtained by a one pot reaction between the functionalized silica, 2-aminophenol and CuCl2. The product obtained has been used as a catalyst for the syntheses of symmetrical diselenides in the presence of KOH as the base and dimethyl sulphoxide (DMSO) as the solvent. The materials have been characterized thoroughly by X-ray powder diffraction, nitrogen adsorption-desorption studies, transmission electron microscopy, thermal analysis and different spectroscopic techniques. The Cu content of the sample has been determined by atomic absorption spectrophotometry (AAS). The products of the catalytic studies have been identified and estimated by NMR spectroscopy. Almost 78% isolated yield could be achieved at 363 K within 3 hours of the reaction and the catalyst, nCuO-FMS, can be recycled at least up to five catalytic cycles.
Metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene: Ortho -quinone methide (VQM)
Huang, Shengli,Chen, Zhili,Mao, Hui,Hu, Fangli,Li, Dongmei,Tan, Yu,Yang, Fengqing,Qin, Wenling
supporting information, p. 1121 - 1129 (2019/02/07)
A metal-free difunctionalization of alkynes to access tetrasubstituted olefins through spontaneous selenosulfonylation of vinylidene ortho-quinone methide (VQM) was described herein. The reaction was conducted under mild conditions without any catalysts or additives. Preliminary mechanism studies revealed that the formation of VQM was the key for this alkyne di-functionalization reaction. The reaction could be applied in the enantioselective asymmetric synthesis of axially chiral styrene. Furthermore, the selenosulfonylation adducts can be transformed into useful naphtho[2,1-b]furan and benzofuran scaffolds.
Catalyst-free gem-difunctionalization of fluoroalkyl-substituted diazo compound with diselenide or disulfide and NFSI
Li, Jiuling,Ma, Chaoqun,Xing, Dong,Hu, Wenhao
supporting information, p. 2101 - 2105 (2019/03/29)
The gem-difunctionalization of fluoroalkyl-substituted diazo compounds by utilizing diselenides or disulfides and NFSI under catalyst-free and mild conditions is reported. A series of gem-aminoselenolation and gem-aminosulfonylation products bearing fluoroalkyl substituents were obtained in high to excellent yields. Different types of conjugated diazo compounds are also applicable to this transformation. Preliminary mechanistic studies indicate that a selenoimidate intermediate generated from diselenide and NFSI is involved for this transformation.
