7652-46-2Relevant articles and documents
Highly stereoselective organocatalytic synthesis of pyrrolidinyl spirooxindoles containing halogenated contiguous quaternary carbon stereocenters
Chen, Fei-Yu,Han, Bo,Kang, Bin,Liu, Hong,Peng, Cheng,Xiang, Li,Zhan, Gu,Zhang, Shu-Cang
, (2020)
The highly stereoselective synthesis of pyrrolidine-fused spirooxindole derivatives bearing a carbon-halogen bond and contiguous quaternary carbon stereocenters was achieved via a [3 + 2] cycloaddition reaction. This method provided facile access to a collection of enantiomerically pure spiro[pyrrolidin-3,2′-oxindoles] containing halogenated contiguous quaternary carbon stereocenters in good to high yields (48–84%) and excellent stereoselectivity (up to >20:1 dr and >99% ee). The halogen-containing products can be stereoselectively transformed into sulfurated derivatives via nucleophilic substitution (SN2) reactions, indicating that they may serve as candidates in the development of covalent inhibitors with potential biological activity.
A simple, convenient method to synthesize cobalamins: Synthesis of homocysteinylcobalamin, N-acetylcysteinylcobalamin, 2-N-acetylamino-2- carbomethoxyethanethiolatocobalamin, sulfitocobalamin and nitrocobalamin
Suarez-Moreira, Edward,Hannibal, Luciana,Smith, Clyde A.,Chavez, Roberto A.,Jacobsen, Donald W.,Brasch, Nicola E.
, p. 5269 - 5277 (2006)
Glutathionylcobalamin, nitrocobalamin and sulfitocobalamin are important cobalamin metabolites isolable from human tissues. Herein we demonstrate that a procedure used to synthesize and isolate γ-glutamylcysteinylcobalamin and glutathionylcobalamin in aqueous solution in high yield and purity can be used to synthesize other novel, biologically relevant thiolatocobalamins, including d,l-homocysteinylcobalamin, N-acetyl-l-cysteinylcobalamin (Na+ salt) and 2-N-acetylamino-2-carbomethoxy-l-ethanethiolatocobalamin, as well as other non-alkylcobalamins, such as sulfitocobalamin (Na+ salt) and nitrocobalamin. This uncomplicated, general procedure will assist researchers in identifying unknown cobalamin metabolites isolated from biological samples, and researchers interested in studying the uptake and intracellular cobalamin processing mechanisms utilizing non-alkylcobalamin derivatives that are not yet commercially available. The X-ray structure and XAS spectrum of N-acetyl-l-cysteinylcobalamin are also presented. The Royal Society of Chemistry 2006.
COMPOUNDS AND IMPLANTS FOR TREATING OCULAR DISORDERS
-
Paragraph 0215, (2021/05/15)
The present disclosure relates to therapeutic compositions and therapies for use in the treatment of diseases and disorders of the eye. The present disclosure relates to curved, multilayer controlled-release ocular implant devices which include the therapeutic compositions of the present disclosure. The present disclosure related to methods for delivery of the therapeutic agents to the eye and the treatment of diseases and disorders of the eye.
Bioorthogonal Ligation and Cleavage by Reactions of Chloroquinoxalines with ortho-Dithiophenols
Fu, Hua,Li, Hongyun,Li, Youshan,Lou, Zhenbang,Yang, Haijun,Zhao, Yufen
supporting information, p. 3671 - 3677 (2020/02/04)
A bioorthogonal ligation and cleavage method via reactions of chloroquinoxalines (CQ) and ortho-dithiophenols (DT) is presented. Double nucleophilic substitutions of ortho-dithiophenols to chloroquinoxalines provide conjugates containing tetracyclic benzo[5,6][1,4]dithiino[2,3-b]quinoxaline with strong built-in fluorescence together with release of the other functional molecules. Three cleavable linkers were designed and successfully used in release of the molecules containing biotin from the protein conjugates. The CQ-DT bioorthogonal reactions can be applied for the bioorthogonal ligations, bioorthogonal cleavages, and trans-tagging of proteins, and show advantages of readily accessible unnatural orthogonal groups, appealing reaction kinetics (k2≈1.3 m?1 s?1), excellent biocompatibility of orthogonal groups, and high stability of conjugates. This complements previous bioorthogonal reactions and is a new route for protein-fishing applications and in-gel fluorescence analysis.
Protection of human retinal pigment epithelial cells from oxidative damage using cysteine prodrugs
Bulumulla, Chandima,Catchpole, Timothy,Christie, Abigail,Csaky, Karl G.,Kularatne, Ruvanthi N.,Stefan, Mihaela C.,Takacs, Alison
, p. 386 - 394 (2020/04/17)
Age-related macular degeneration (AMD) is one of the major causes of vision loss in the elderly in most developed countries. Among other causes, oxidative stress in the retinal pigment epithelium (RPE) has been hypothesized to be a major driving force of AMD pathology. Oxidative stress could be treated by antioxidant administration into the RPE cells. However, to achieve high in-vivo efficacy of an antioxidant, it is imperative that the agent be able to penetrate the tissues and cells. Evidence suggests that lipophilicity governs cellular penetrance. Out of many antioxidant candidates, N-acetyl-L-cysteine (a prodrug of L-cysteine) (NAC) is a potent antioxidant as the bioavailability of the parent drug, L-cysteine, determines the production of glutathione; the universal antioxidant that regulates ROS. To increase the lipophilicity, four ester derivatives of N-acetylcysteine: N-acetylcysteine methyl ester, N-acetylcysteine ethyl ester, N-acetylcysteine propyl ester, and N-acetylcysteine butyl ester were synthesized. To mimic in vitro AMD conditions, hydroquinone, a component of cigarette smoke, was used as the oxidative insult. Cytosolic and mitochondrial protection against oxidative stress were tested using cytosolic and mitochondrial specific assays. The results provide evidence that these lipophilic cysteine prodrugs provide increased protection against oxidative stress in human RPE cells compared with NAC.
Visible-Light-Mediated S?H Bond Insertion Reactions of Diazoalkanes with Cysteine Residues in Batch and Flow
Chen, Lin,Cui, Yu-Sheng,Duan, Xiu,Guo, Kai,Qin, Long-Zhou,Qiu, Jiang-Kai,Sun, Qi,Yuan, Xin,Zhuang, Kai-Qiang
supporting information, p. 5093 - 5104 (2020/09/23)
We describe the application of S?H bond insertion reactions of aryl diazoacetates with cysteine residues that enabled metal-free, S?H functionalization under visible-light conditions. Moreover, this process could be intensified by a continuous-flow photomicroreactor on the acceleration of the reaction (6.5 min residence time). The batch and flow protocols described were applied to obtain a wide range of functionalized cysteine derivatives and cysteine-containing dipeptides, thus providing a straightforward and general platform for their functionalizations in mild conditions. (Figure presented.).
NOVEL COMPOUND EXHIBITING ANTI-OXIDATIVE OR ANTI-INFLAMMATORY ACTIVITY
-
Paragraph 0092-0095, (2019/07/29)
The present invention relates to a novel compound exhibiting anti-oxidative or anti-inflammatory activity, a method of preparing the compound, a pharmaceutical composition for preventing or treating inflammatory diseases or the diseases caused by oxidation, which comprises the compound or a salt thereof as an active ingredient, and an anti-inflammatory or anti-oxidative cosmetic composition or food composition.
Labeling and Natural Post-Translational Modification of Peptides and Proteins via Chemoselective Pd-Catalyzed Prenylation of Cysteine
Schlatzer, Thomas,Kriegesmann, Julia,Schr?der, Hilmar,Trobe, Melanie,Lembacher-Fadum, Christian,Santner, Simone,Kravchuk, Alexander V.,Becker, Christian F. W.,Breinbauer, Rolf
supporting information, p. 14931 - 14937 (2019/10/11)
The prenylation of peptides and proteins is an important post-translational modification observed in vivo. We report that the Pd-catalyzed Tsuji-Trost allylation with a Pd/BIPHEPHOS catalyst system allows the allylation of Cys-containing peptides and proteins with complete chemoselectivity and high n/i regioselectivity. In contrast to recently established methods, which use non-native connections, the Pd-catalyzed prenylation produces the natural n-prenylthioether bond. In addition, a variety of biophysical probes such as affinity handles and fluorescent tags can be introduced into Cys-containing peptides and proteins. Furthermore, peptides containing two cysteine residues can be stapled or cyclized using homobifunctional allylic carbonate reagents.
Modulating Thiol p Ka Promotes Disulfide Formation at Physiological pH: An Elegant Strategy to Design Disulfide Cross-Linked Hyaluronic Acid Hydrogels
Bermejo-Velasco, Daniel,Azémar, Alice,Oommen, Oommen P.,Hilborn, J?ns,Varghese, Oommen P.
, p. 1412 - 1420 (2019/03/02)
The disulfide bond plays a crucial role in protein biology and has been exploited by scientists to develop antibody-drug conjugates, sensors, and for the immobilization other biomolecules to materials surfaces. In spite of its versatile use, the disulfide chemistry suffers from some inevitable limitations such as the need for basic conditions (pH > 8.5), strong oxidants, and long reaction times. We demonstrate here that thiol-substrates containing electron-withdrawing groups at the β-position influence the deprotonation of the thiol group, which is the key reaction intermediate in the formation of disulfide bonds. Evaluation of reaction kinetics using small molecule substrate such as l-cysteine indicated disulfide formation at a 2.8-fold higher (k1 = 5.04 × 10-4 min-1) reaction rate as compared to the conventional thiol substrate, namely 3-mercaptopropionic acid (k1 = 1.80 × 10-4 min-1) at physiological pH (pH 7.4). Interestingly, the same effect could not be observed when N-acetyl-l-cysteine substrate (k1 = 0.51 × 10-4 min-1) was used. We further grafted such thiol-containing molecules (cysteine, N-acetyl-cysteine, and 3-mercaptopropionic acid) to a biopolymer namely hyaluronic acid (HA) and determined the pKa value of different thiol groups by spectrophotometric analysis. The electron-withdrawing group at the β-position reduced the pKa of the thiol group to 7.0 for HA-cysteine (HA-Cys); 7.4 for N-acetyl cysteine (HA-ActCys); and 8.1 for HA-thiol (HA-SH) derivatives, respectively. These experiments further confirmed that the concentration of thiolate (R-S-) ions could be increased with the presence of electron-withdrawing groups, which could facilitate disulfide cross-linked hydrogel formation at physiological pH. Indeed, HA grafted with cysteine or N-acetyl groups formed hydrogels within 3.5 min or 10 h, respectively, at pH 7.4. After completion of cross-linking reaction, both gels demonstrated a storage modulus G′ ≈ 3300-3500 Pa, which indicated comparable levels of cross-linking. The HA-SH gel, on the other hand, did not form any gel at pH 7.4 even after 24 h. Finally, we demonstrated that the newly prepared hydrogels exhibited excellent hydrolytic stability but can be degraded by cell-directed processes (enzymatic and reductive degradation). We believe our study provides a valuable insight on the factors governing the disulfide formation and our results are useful to develop strategies that would facilitate generation of stable thiol functionalized biomolecules or promote fast thiol oxidation according to the biomedical needs.
Chemoselective Synthesis of N-Terminal Cysteinyl Thioesters via β,γ-C,S Thiol-Michael Addition
Petracca, Rita,Bowen, Katherine A.,McSweeney, Lauren,O'Flaherty, Siobhan,Genna, Vito,Twamley, Brendan,Devocelle, Marc,Scanlan, Eoin M.
supporting information, p. 3281 - 3285 (2019/05/10)
Dehydroalanine (ΔAla) is a highly electrophilic residue that can react efficiently with sulfur nucleophiles to furnish cysteinyl analogues. Herein, we report an efficient synthesis of N-terminal cysteinyl thioesters, suitable for S,N-acyl transfer, based on β,γ-C,S thiol-Michael addition. Both ionic and radical-based methodologies were found to be efficient for this process.
