37031-12-2Relevant articles and documents
Seleno-Michael Reaction of Stable Functionalised Alkyl Selenols: A Versatile Tool for the Synthesis of Acyclic and Cyclic Unsymmetrical Alkyl and Vinyl Selenides
Tanini, Damiano,Scarpelli, Simone,Ermini, Elena,Capperucci, Antonella
, p. 2337 - 2346 (2019)
Seleno-Michael additions of stable functionalised primary alkyl selenols to activated alkenes and alkynes are described. In the presence of Al2O3, β-hydroxy-, β-amino-, and β-mercapto selenols react smoothly with electron-poor alkenes and alkynes to afford the corresponding unsymmetrical functionalised dialkyl- and alkyl?vinyl-selenides in good yield. The very mild conditions allow a broad range of selenols and Michael acceptors to be converted into the corresponding synthetically valuable seleno-Michael adducts, demonstrating high selectivity and excellent functional group tolerance. Hydroxy- and mercapto-substituted vinyl selenides were efficiently employed for the synthesis of functionalised 1,3-oxaselenolanes, 1,3-thiaselenolanes, and 1,4-thiaselenanes through intramolecular oxa- and thia-Michael additions. Furthermore, a NaH-promoted lactonization enables the synthesis of variously substituted 2-oxo-1,4-oxaselenanes from hydroxy?vinyl-selenides. Evaluation of thiol peroxidase-like properties of novel functionalised organoselenides demonstrated that they possess a remarkable catalytic antioxidant activity. (Figure presented.).
Efficient resolution of oxidized Cleland's reagent by C2-symmetric BOC- L-phenylalanyl esters
Evans, Colleen A.,Bernier, Louise,Dugas, Josee,Mansour, Tarek S.
, p. 7657 - 7660 (1997)
Trans 4,5-dihydroxy-1,2-dithiane (1,oxidized form of Cleland's reagent; dithiothreitol) is resolved efficiently in > 99% overall e.e. into its two enantiomers by fractional recrystallization of its BOC-L-phenylalanyl diesters.
Selective, Modular Probes for Thioredoxins Enabled by Rational Tuning of a Unique Disulfide Structure Motif
Becker, Katja,Busker, Sander,Felber, Jan G.,Maier, Martin S.,Poczka, Lena,Scholzen, Karoline,Theisen, Ulrike,Thorn-Seshold, Julia,Thorn-Seshold, Oliver,Zeisel, Lukas,Arnér, Elias S. J.,Brandst?dter, Christina
supporting information, p. 8791 - 8803 (2021/06/27)
Specialized cellular networks of oxidoreductases coordinate the dithiol/disulfide-exchange reactions that control metabolism, protein regulation, and redox homeostasis. For probes to be selective for redox enzymes and effector proteins (nM to μM concentrations), they must also be able to resist non-specific triggering by the ca. 50 mM background of non-catalytic cellular monothiols. However, no such selective reduction-sensing systems have yet been established. Here, we used rational structural design to independently vary thermodynamic and kinetic aspects of disulfide stability, creating a series of unusual disulfide reduction trigger units designed for stability to monothiols. We integrated the motifs into modular series of fluorogenic probes that release and activate an arbitrary chemical cargo upon reduction, and compared their performance to that of the literature-known disulfides. The probes were comprehensively screened for biological stability and selectivity against a range of redox effector proteins and enzymes. This design process delivered the first disulfide probes with excellent stability to monothiols yet high selectivity for the key redox-Active protein effector, thioredoxin. We anticipate that further applications of these novel disulfide triggers will deliver unique probes targeting cellular thioredoxins. We also anticipate that further tuning following this design paradigm will enable redox probes for other important dithiol-manifold redox proteins, that will be useful in revealing the hitherto hidden dynamics of endogenous cellular redox systems.
Disulfide-Unit Conjugation Enables Ultrafast Cytosolic Internalization of Antisense DNA and siRNA
Shu, Zhaoma,Tanaka, Iku,Ota, Azumi,Fushihara, Daichi,Abe, Naoko,Kawaguchi, Saki,Nakamoto, Kosuke,Tomoike, Fumiaki,Tada, Seiichi,Ito, Yoshihiro,Kimura, Yasuaki,Abe, Hiroshi
supporting information, p. 6611 - 6615 (2019/04/10)
Development of intracellular delivery methods for antisense DNA and siRNA is important. Previously reported methods using liposomes or receptor-ligands take several hours or more to deliver oligonucleotides to the cytoplasm due to their retention in endosomes. Oligonucleotides modified with low molecular weight disulfide units at a terminus reach the cytoplasm 10 minutes after administration to cultured cells. This rapid cytoplasmic internalization of disulfide-modified oligonucleotides suggests the existence of an uptake pathway other than endocytosis. Mechanistic analysis revealed that the modified oligonucleotides are efficiently internalized into the cytoplasm through disulfide exchange reactions with the thiol groups on the cellular surface. This approach solves several critical problems with the currently available methods for enhancing cellular uptake of oligonucleotides and may be an effective approach in the medicinal application of antisense DNA and siRNA.
