- Lead optimization generates selenium-containing miconazole CYP51 inhibitors with improved pharmacological profile for the treatment of fungal infections
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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.
- Xu, Hang,Yan, Zhong-zuo,Guo, Meng-bi,An, Ran,Wang, Xin,Zhang, Rui,Mou, Yan-hua,Hou, Zhuang,Guo, Chun
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- Nickel-Catalyzed Intramolecular Decarbonylative Coupling of Aryl Selenol Esters
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This report describes a method for Ni-catalyzed intramolecular decarbonylative coupling, which enables the conversion of areneselenol esters to diaryl selenides. The inexpensive and readily available catalyst can be employed under mild reaction conditions for the construction of structurally diverse diaryl selenides, including heterocyclic and natural product derivatives. (Figure presented.).
- Bai, Jin-Hua,Qi, Xiu-Juan,Sun, Wei,Yu, Tian-Yang,Xu, Peng-Fei
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supporting information
p. 2084 - 2088
(2021/03/01)
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- Green preparation method of aryl diselenium ether type organic selenium compound
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The invention discloses an aryl diselenium ether compound synthesis method. The synthesis method comprises the following steps: taking the compound represented by the formula (I) as a reaction raw material, CuBr as a catalyst, KOH in the condition Se, a reducing agent, a disproportionation reaction, water or ethanol as a solvent, and 60 °C. After completion of the reaction, the obtained reaction solution is subjected to post-treatment (if ethanol is recovered as solvent) to obtain the aryl diselenoether compound represented by the formula (II), the yield is close 100%, the subsequent treatment is simple, and a complex separation and purification method is not needed to obtain a pure product. The solvent is recovered as a solvent such as ethanol. , It is preferable. The method is more green. Economy, high efficiency, environmental protection.
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Paragraph 0057-0061
(2021/11/14)
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- Metal-free chalcogenation of cycloketone oxime esters with dichalcogenides
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We report the metal-free chalcogenation of cycloketone oxime esters with dichalcogenides via a radical process. Because of the metal-free condition and use of readily accessible dichalcogenides, this method is an effective and green strategy for the synthesis of chalcogen-substituted butyronitrile.
- Ji, Liangshuo,Qiao, Jiamin,Liu, Junjie,Tian, Miaomiao,Lu, Kui,Zhao, Xia
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supporting information
(2021/06/15)
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- Metal-free synthesis of unsymmetrical selenides from pyridinium salts and diselenides catalysed by visible light
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We report the first metal-free selenolations of pyridinium salts with diselenides to prepare unsymmetrical organoselenides catalysed by visible light. This protocol is an efficient and green method for the preparation of unsymmetrical organoselenides because metal-free conditions and readily accessible diselenides are used.
- Ji, Liangshuo,Qiao, Jiamin,Li, Ankun,Jiang, Zeyi,Lu, Kui,Zhao, Xia
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supporting information
(2021/05/04)
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- Rhodium-Catalyzed Enantioselective Hydroselenation of Heterobicyclic Alkenes
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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.
- Li, Sifeng,Yang, Qingjing,Bian, Zhaoxiang,Wang, Jun
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supporting information
p. 2781 - 2785
(2020/03/30)
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- Synthesis of organoselenyl isoquinolinium imidesviairon(iii) chloride-mediated tandem cyclization/selenation ofN′-(2-alkynylbenzylidene)hydrazides and diselenides
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This report describes the synthesis of organoselenyl isoquinolinium imides through a tandem cyclization betweenN′-(2-alkynylbenzylidene)hydrazides and diselenides. The reaction was carried out at room temperature under an ambient atmosphere using cheap iron(iii) chloride as the metallic source. The strategy shows good tolerance to a broad range ofN′-(2-alkynylbenzylidene)hydrazides and diselenides, and forms C-N and C-Se bonds in one step. The obtained product is further transformed into a bioactiveH-pyrazolo[5,1-a]isoquinoline skeleton easilyviaa silver catalyzed [3 + 2] cycloaddition.
- Cai, Zhong-Jian,Ji, Shun-Jun,Li, Fang-Hui,Wang, Dian-Liang,Wu, Bing,Yao, Hai-Feng
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supporting information
p. 7577 - 7584
(2020/10/14)
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- One-pot preparation of (RSe)2CF2 and (RS)2CF2 compounds via insertion of TMSCF3-derived difluorocarbene into diselenides and disulfides
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A method for the first direct insertion of difluorcarbene, generated from TMSCF3, into diselenides and disulfides is disclosed, producing novel difluoromethyl diselenoacetals and difluoromethyl dithioacetals. The reaction conditions tolerate a range of synthetically useful and biologically relevant functional groups. The process is scalable, with two representative compounds prepared at a gram-scale in good yields, and it utilizes cheap and available reagents.
- Barrett, Colby,Krishnamurti, Vinayak,Oliveira, Artur Pratas,Prakash, G.K. Surya
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p. 4167 - 4173
(2019/04/30)
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- Metal-Free ipso -Selenocyanation of Arylboronic Acids Using Malononitrile and Selenium Dioxide
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The first ipso -selenocyanation of arylboronic acids is achieved using selenium dioxide and malononitrile under mild conditions. The reaction is successful even without metal or base in DMSO. The major advantages of this new method are an easy set-up, excellent yields, and the use of odorless and inexpensive selenium reagents. Basic conditions subsequently afford new access to diaryldiselenides in good yields without isolating the organoselenocyanate intermediates.
- Broggi, Julie,Kosso, Anne Roly Obah,Redon, Sébastien,Vanelle, Patrice
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supporting information
p. 3758 - 3764
(2019/09/30)
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- Trifluoromethylthiolative 1,2-difunctionalization of alkenes with diselenides and AgSCF3
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An efficient regioselective difunctionalization of alkenes via trifluoromethylthiolation has been accomplished employing diaryl diselenide and AgSCF3 in the presence of BF3·OEt2. Various substituted 1,2-dichalcogenated products having the SCF3 moiety were synthesized in good to excellent yields under mild conditions. The preliminary mechanistic investigation revealed the possible reaction pathway and unique combination of diselenide and AgSCF3 for successful transformation.
- Saravanan, Perumal,Anbarasan, Pazhamalai
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supporting information
p. 4639 - 4642
(2019/05/02)
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- Preparation method for diphenyl diselenium compound
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The invention discloses a preparation method for a diphenyl diselenium compound. According to the method, an arylboronic acid compound and elemental selenium serve as reaction raw materials, an organic solvent serves as a reaction solvent, under the effect of a silver catalyst, reaction is carried out so as to obtain the diphenyl diselenium compound, the reaction temperature is 100-140 DEG C, thereaction equation is shown in the specification, wherein R is a benzene ring, a naphthalene ring, a heterocyclic ring or a substituted benzene ring. The method has the beneficial effects that the tolerance of functional groups of substrates is high, and the range of the substrates is wide; and the raw materials and the catalyst are cheap and easily available, the conditions are mild, the post-treatment is simple, the yield and purity of a product are high, and the method is suitable for large-scale industrial production.
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Paragraph 0051-0053
(2018/06/28)
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- Chain-Breaking Phenolic 2,3-Dihydrobenzo[b]selenophene Antioxidants: Proximity Effects and Regeneration Studies
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Phenolic 2,3-dihydrobenzo[b]selenophene antioxidants bearing an OH-group ortho (9), meta (10, 11) and para (8) to the Se were prepared by seleno-Claisen rearrangement/intramolecular hydroselenation. meta-Isomer (11) was studied by X-ray crystallography. The radical-trapping activity and regenerability of compounds 8–11 were evaluated using a two-phase system in which linoleic acid was undergoing peroxidation in the lipid phase while regeneration of the antioxidant by co-antioxidants (N-acetylcysteine, glutathione, dithiothreitol, ascorbic acid, tris(carboxyethyl)phosphine hydrochloride) was ongoing in the aqueous layer. Compound 9 quenched peroxyl radicals more efficiently than α-tocopherol. It also provided the most long-lasting antioxidant protection. With thiol co-antioxidants it could inhibit peroxidation for more than five-fold longer than the natural product. Regeneration was more efficient when the aqueous phase pH was slightly acidic. Since calculated O?H bond dissociation energies for 8–11 were substantially larger than for α-tocopherol, an antioxidant mechanism involving O-atom transfer from peroxyl to selenium was proposed. The resulting phenolic selenoxide/alkoxyl radical would then exchange a hydrogen atom in a solvent cage before antioxidant regeneration at the aqueous lipid interphase.
- Singh, Vijay P.,Yan, Jiajie,Poon, Jia-Fei,Gates, Paul J.,Butcher, Ray J.,Engman, Lars
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p. 15080 - 15088
(2017/10/17)
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- Copper-catalyzed one-pot tandem synthesis of unsymmetrical diaryl chalcogenides from two different aryl iodides
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Unsymmetrical diaryl chalcogenides were synthesized by a novel one-pot tandem process from two different aryl iodides. A symmetrical diaryl dichalcogenide (ArEEAr, E = Se or Te) was initially obtained by a Cu2O-cataylzed coupling reaction of Ar
- Zhang, Shaozhong,Koe, Adam,Heintz, Christina,Senior, Aunajay,Jin, Jin
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supporting information
p. 260 - 263
(2016/01/12)
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- α-Arylchalcogenation of acetone with diaryl dichalcogenide via metal-free oxidative C(sp3)-H bond functionalization
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Direct α-arylchalcogenation of acetone with diaryl dichalcogenides has been achieved by using a mixture of TBHP and DTBP oxidants at 120 °C without transition-metal catalyst via oxidative C(sp3)-H bond functionalization. The method exhibits good functional group tolerance and products were isolated in moderate to high yields.
- Yan, Guobing,Borah, Arun Jyoti,Wang, Lianggui,Pan, Zhangjin,Chen, Shuangshuang,Shen, Xuqian,Wu, Xiangmei
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supporting information
p. 4305 - 4307
(2015/06/22)
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- Synthesis of disulfides and diselenides by copper-catalyzed coupling reactions in water
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A simple and efficient protocol for copper-catalyzed coupling reactions between aryl halides and elemental sulfur or selenium has been developed. A variety of disulfides and diselenides can be obtained in moderate to excellent yields up to 96%. The Royal Society of Chemistry 2013.
- Li, Zhengkai,Ke, Fang,Deng, Hang,Xu, Hualong,Xiang, Haifeng,Zhou, Xiangge
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supporting information
p. 2943 - 2946
(2013/07/25)
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- Iron-catalyzed formation of C-Se and C-Te bonds through cross coupling of aryl halides with Se(0) and Te(0)/nano-Fe3O4@GO
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The formation of C-Se and C-Te bonds is of synthetic and biological importance. Graphene oxide based nano-Fe3O4 (nano-Fe 3O4@GO) is used as a reusable catalyst for the efficient synthesis of diselenides and ditellurides, through cross coupling of Se(0) or Te(0) with aryl iodides. The magnetic heterogeneous catalyst could be easily recovered and reused many times without significant loss of catalytic activity. In addition the superiority of nano-Fe3O4@GO over pristine nano-Fe3O4 is established. Georg Thieme Verlag Stuttgart. New York.
- Kassaee, Mohammadzaman,Motamedi, Elaheh,Movassagh, Barahman,Poursadeghi, Samira
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p. 2337 - 2342
(2013/09/02)
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- Microwave-assisted one-pot synthesis of symmetrical diselenides, ditellurides and disulfides from organoyl iodides and elemental chalcogen catalyzed by CuO nanoparticles
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In this study CuO nanoparticles were applied as a catalyst for CSe, CTe, and CS bond formation. The reaction was performed with organoyl iodides and elemental selenium, tellurium or sulfur under microwave irradiation in the presence of a base and solvent at 80 °C. This novel protocol allowed the synthesis of a variety of diselenides, ditellurides and disulfides in good to excellent yields in a very short reaction time.
- Botteselle, Giancarlo V.,Godoi, Marcelo,Galetto, Fabio Z.,Bettanin, Luana,Singh, Devender,Rodrigues, Oscar E.D.,Braga, Antonio L.
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p. 186 - 193
(2013/01/14)
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- An efficient one-pot synthesis of symmetrical diselenides or ditellurides from halides with CuO nanopowder/Se0 or Te0/base
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(Equation Presented). A CuO nanopowder-catalyzed coupling reaction of aryl, alkyl, and heteroaryl iodides with elemental selenium and tellurium takes place in the presence of KOH at 90 °C in DMSO. A wide range of substituted symmetrical diselenides and ditellurides were afforded with good to excellent yields.
- Singh, Devender,Deobald, Anna M.,Camargo, Leandro R.S.,Tabarelli, Greice,Rodrigues, Oscar E.D.,Braga, Antonio L.
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supporting information; experimental part
p. 3288 - 3291
(2010/09/30)
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- Facile synthesis of 4H-1,3-benzoselenazines by the aryne reaction
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Attempts to prepare benzoselenazoles by trapping benzynes with selenoureas failed. These reactions gave instead symmetrically substituted diaryl diselenides. However, when the selenoureas were converted to selenoazadienes, 4H-1,3-benzoselenazines were obtained in excellent yields. Furthermore, addition of the selenium atom of the selenoazadienes occurred regioselectively at the position 1 of 3-methoxybenzyne and 3,4-dimethoxybenzyne.
- Rao, U. Narasimha,Sathunuru, Ramadas,Biehl, Edward R.
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p. 1067 - 1075
(2007/10/03)
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- NEW SYNTHETIC METHODS : SODIUM ALKANECHALCOGENATES AS DEMETHYLATING AGENTS. SCOPE, LIMITATION AND NEW ONE-POT SYNTHESIS OF DIARYLDISELENIDES.
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Sodium alkanechalcogenates (S, Se) cleave the alkylarylchalcogenides (O, S, Se).The versatility of such reagents is developed and applied to a new synthesis of diaryldiselenides.
- Evers, Michel,Christiaens, Leon
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p. 377 - 380
(2007/10/02)
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