62212-22-0Relevant articles and documents
Synthesis of Dibenzylic Diselenides from Elemental Selenium and Benzylic Quaternary Ammonium Salts
Chen, Feng,Li, Fuhai,Zeng, Qingle
, p. 5605 - 5608 (2021/11/11)
Abstract: Substituted dibenzyl diselenides are synthesized in good yields (74–91 %) by SN2 nucleophilic substitution of benzylic trimethylammonium salts and diselenide dianion (Se2?), in situ generated from elemental selenium, under
Toward Enantiomerically Pure β-Seleno-α-amino Acids via Stereoselective Se-Michael Additions to Chiral Dehydroalanines
Oroz, Paula,Navo, Claudio D.,Avenoza, Alberto,Busto, Jesús H.,Corzana, Francisco,Jiménez-Osés, Gonzalo,Peregrina, Jesús M.
supporting information, p. 1955 - 1959 (2021/01/13)
The first totally chemo- and diastereoselective 1,4-conjugate additions of Se-nucleophiles to a chiral bicyclic dehydroalanine (Dha) are described. The methodology is simple and does not require any catalyst, providing exceptional yields at room temperature, and involves the treatment of the corresponding diselenide compound with NaBH4 in the presence of the Dha. These Se-Michael additions provide an excellent channel for the synthesis of enantiomerically pure selenocysteine (Sec) derivatives, which pose high potential for chemical biology applications.
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.
Synthesis of unsymmetrical glycosyl diselenides by the treatment of symmetrical diselenides with glycosyl selenocyanates
Manna, Tapasi,Misra, Anup Kumar,Rana, Abhijit
, (2021/08/03)
A novel reaction condition has been developed for the synthesis of unsymmetrical glycosyl diselenide derivatives in excellent yield by the reaction of glycosyl selenocyanates as selenol surrogates with symmetrical diselenides in the presence of hydrazine monohydrate at room temperature. The reaction metal-free condition is reasonably fast, simple, non-malodorous and suitable for scale-up.
Design, synthesis, and biological evaluation of novel miconazole analogues containing selenium as potent antifungal agents
An, Ran,Guo, Chun,Guo, Meng-bi,Hou, Zhuang,Mou, Yan-hua,Su, Xin,Xu, Hang
, (2020/05/11)
Herein, based on the theory of bioisosterism, a series of novel miconazole analogues containing selenium were designed, synthesized and their inhibitory effects on thirteen strains of pathogenic fungi were evaluated. It is especially encouraging that all the novel target compounds displayed significant antifungal activities against all tested strains. Furthermore, all the target compounds showed excellent inhibitory effects on fluconazole-resistant fungi. Subsequently, preliminary mechanistic studies indicated that the representative compound A03 had a strong inhibitory effect on C.alb. CYP51. Moreover, the target compounds could prevent the formation of fungi biofilms. Further hemolysis test verified that potential compounds had higher safety than miconazole. In addition, molecular docking study provided the interaction modes between the target compounds and C.alb. CYP51. These results strongly suggested that some target compounds are promising as novel antifungal drugs.
Multistep Synthesis of Organic Selenides under Visible Light Irradiation: A Continuous-Flow Approach
Heredia, Adrián A.,Soria-Castro, Silvia M.,Castro-Godoy, Willber D.,Lemir, Ignacio D.,López-Vidal, Martín,Bisogno, Fabricio R.,Argüello, Juan E.,Oksdath-Mansilla, Gabriela
supporting information, p. 540 - 545 (2020/03/26)
The potential application of multistep continuous-flow systems has had a great impact on the syntheses of active pharmaceutical ingredients, natural products, and commodity chemicals. In this report, the highly efficient combination of a chemical reduction and a photochemical Csp2-H activation reaction for selenylation of biologically relevant electron-rich arenes was achieved by means of a continuous-flow process. First, the reduction of alkyl and aryl selenocyanates by Rongalite was achieved giving the corresponding diselenides; second, the photoactivation of the Se-Se bond resulted in the selenylation of electron-rich arenes, both steps from good to excellent yields. In all cases, the reaction time was shortened, and isolated yields were improved when compared to batch reaction conditions. Furthermore, connecting both reactions in a multistep continuous-flow sequence was possible even when reductive and photooxidative transformations were coupled.
Rational design of an organocatalyst for peptide bond formation
Handoko,Satishkumar, Sakilam,Panigrahi, Nihar R.,Arora, Paramjit S.
supporting information, p. 15977 - 15985 (2019/10/11)
Amide bonds are ubiquitous in peptides, proteins, pharmaceuticals, and polymers. The formation of amide bonds is a straightforward process: amide bonds can be synthesized with relative ease because of the availability of efficient coupling agents. However, there is a substantive need for methods that do not require excess reagents. A catalyst that condenses amino acids could have an important impact by reducing the significant waste generated during peptide synthesis. We describe the rational design of a biomimetic catalyst that can efficiently couple amino acids featuring standard protecting groups. The catalyst design combines lessons learned from enzymes, peptide biosynthesis, and organocatalysts. Under optimized conditions, 5 mol % catalyst efficiently couples Fmoc amino acids without notable racemization. Importantly, we demonstrate that the catalyst is functional for the synthesis of oligopeptides on solid phase. This result is significant because it illustrates the potential of the catalyst to function on a substrate with a multitude of amide bonds, which may be expected to inhibit a hydrogen-bonding catalyst.
Accelerated Protein Synthesis via One-Pot Ligation-Deselenization Chemistry
Mitchell, Nicholas J.,Sayers, Jessica,Kulkarni, Sameer S.,Clayton, Daniel,Goldys, Anna M.,Ripoll-Rozada, Jorge,Barbosa Pereira, Pedro José,Chan, Bun,Radom, Leo,Payne, Richard J.
, p. 703 - 715 (2017/05/15)
Peptide ligation chemistry has revolutionized protein science by facilitating access to synthetic proteins. Here, we describe the development of additive-free ligation-deselenization chemistry at β-selenoaspartate and γ-selenoglutamate that enables the generation of native polypeptide products on unprecedented timescales. The deselenization step is chemoselective in the presence of unprotected selenocysteine, which is highlighted in the synthesis of selenoprotein K. The power of the methodology is also showcased through the synthesis of three tick-derived thrombin-inhibiting proteins, each of which were assembled, purified, and isolated for biological assays within a few hours. The methodology described here should serve as a powerful means of accessing synthetic proteins, including therapeutic leads, in the future.
Alternative Protocol for the Synthesis of Symmetrical Dibenzyl Diselenides and Disulfides
Panduranga, Veladi,Prabhu, Girish,Panguluri, Nageswara Rao,Sureshbabu, Vommina V.
, p. 1711 - 1718 (2016/06/01)
A one-pot protocol for the preparation of symmetrical dibenzyl diselenides and disulfides from the corresponding benzyl alcohols employing NaBH2Se3 and NaBH2S3 as selenium-transfer and sulfur-transfer reagent, respectively, is described. Structurally diverse substituted benzyl alcohols afforded the corresponding diselenides and disulfides in good to excellent yields. The protocol is simple and mild, and the products were obtained within a short reaction time.
Preparation of the β2-homoselenocysteine derivatives Fmoc-(S)-β2hSec(PMB)-OH and Boc-(S)-β2hSec(PMB)- OH for solution and solid-phase peptide synthesis
Patora-Komisarska, Krystyna,Jadwiga Podwysocka, Dominika,Seebach, Dieter
body text, p. 1 - 17 (2011/03/17)
Fmoc-β2hSer(tBu)-OH was converted to Fmoc-β2hSec(PMB)-OH in five steps. To avoid elimination of HSeR, the selenyl group was introduced in the second last step (Fmoc- β2hSer(Ts)-OAll→Fmoc-β2hSec(PMB)-OAll). In a similar way, the N-Boc-protected compound was prepared. With the β2hSe-derivatives, 21 β2-amino-acid building blocks with proteinogenic side chains are now available for peptide synthesis. Copyright
