6992-30-9Relevant academic research and scientific papers
HETEROCYCLIC-DITHIOL CLICK CHEMISTRY
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Paragraph 00186; 00187, (2019/02/02)
Disclosed are polymers, methods of making polymers, and compositions, focused on cross-linking heterocycles comprising a moiety of Formula I with thiols and thiolates.
Cyclic Thiosulfinates and Cyclic Disulfides Selectively Cross-Link Thiols while Avoiding Modification of Lone Thiols
Donnelly, Daniel P.,Dowgiallo, Matthew G.,Salisbury, Joseph P.,Aluri, Krishna C.,Iyengar, Suhasini,Chaudhari, Meenal,Mathew, Merlit,Miele, Isabella,Auclair, Jared R.,Lopez, Steven A.,Manetsch, Roman,Agar, Jeffrey N.
supporting information, p. 7377 - 7380 (2018/06/11)
This work addresses the need for chemical tools that can selectively form cross-links. Contemporary thiol-selective cross-linkers, for example, modify all accessible thiols, but only form cross-links between a subset. The resulting terminal "dead-end" modifications of lone thiols are toxic, confound cross-linking-based studies of macromolecular structure, and are an undesired, and currently unavoidable, byproduct in polymer synthesis. Using the thiol pair of Cu/Zn-superoxide dismutase (SOD1), we demonstrated that cyclic disulfides, including the drug/nutritional supplement lipoic acid, efficiently cross-linked thiol pairs but avoided dead-end modifications. Thiolate-directed nucleophilic attack upon the cyclic disulfide resulted in thiol-disulfide exchange and ring cleavage. The resulting disulfide-tethered terminal thiolate moiety either directed the reverse reaction, releasing the cyclic disulfide, or participated in oxidative disulfide (cross-link) formation. We hypothesized, and confirmed with density functional theory (DFT) calculations, that mono-S-oxo derivatives of cyclic disulfides formed a terminal sulfenic acid upon ring cleavage that obviated the previously rate-limiting step, thiol oxidation, and accelerated the new rate-determining step, ring cleavage. Our calculations suggest that the origin of accelerated ring cleavage is improved frontier molecular orbital overlap in the thiolate-disulfide interchange transition. Five- to seven-membered cyclic thiosulfinates were synthesized and efficiently cross-linked up to 104-fold faster than their cyclic disulfide precursors; functioned in the presence of biological concentrations of glutathione; and acted as cell-permeable, potent, tolerable, intracellular cross-linkers. This new class of thiol cross-linkers exhibited click-like attributes including, high yields driven by the enthalpies of disulfide and water formation, orthogonality with common functional groups, water-compatibility, and ring strain-dependence.
Preparation method of thioctic acid oxidation impurities
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Paragraph 0028; 0029, (2017/07/22)
The invention relates to a chemical preparation method of thioctic acid oxidation impurities, and belongs to the technical field of medicine synthesis. The structural formula of the thioctic acid oxidation impurities is shown in the description. The preparation method of the thioctic acid oxidation impurities comprises the following steps: preparing an ester from thioctic acid and an alcohol in an organic solvent under the action of a condensing agent; dissolving the obtained alcohol ester compound of thioctic acid in an organic solvent, processing the obtained solution by an oxidant to generate four oxidation products of thioctate, and carrying out column chromatography purification according to the Rf vale difference of the compounds to obtain four intermediate compounds; and respectively hydrolyzing the four intermediate compounds in an alkaline aqueous solution to obtain the four thioctic acid oxidation impurity compounds I, II, III and IV. The preparation method of the thioctic acid oxidation impurity compounds has the advantages of obtaining of single oxidation impurities, simplicity, easiness in implementation, and easiness in enforcement.
Oxidation of disulfides to thiolsulfinates with hydrogen peroxide and a cyclic seleninate ester catalyst peroxide and a cyclic seleninate ester catalyst
McNeil, Nicole M. R.,McDonnell, Ciara,Hambrook, Miranda,Back, Thomas G.
, p. 10748 - 10762 (2015/08/11)
Cyclic seleninate esters function as mimetics of the antioxidant selenoenzyme glutathione peroxidase. They catalyze the reduction of harmful peroxides with thiols, which are converted to disulfides in the process. The possibility that the seleninate esters could also catalyze the further oxidation of disulfides to thiolsulfinates and other overoxidation products under these conditions was investigated. This has ramifications in potential medicinal applications of seleninate esters because of the possibility of catalyzing the unwanted oxidation of disulfide-containing spectator peptides and proteins. A variety of aryl and alkyl disulfides underwent facile oxidation with hydrogen peroxide in the presence of catalytic benzo-1,2-oxaselenolane Se-oxide affording the corresponding thiolsulfinates as the principal products. Unsymmetrical disulfides typically afforded mixtures of regioisomers. Lipoic acid and N,N′-dibenzoylcystine dimethyl ester were oxidized readily under similar conditions. Although isolated yields of the product thiolsulfinates were generally modest, these experiments demonstrate that the method nevertheless has preparative value because of its mild conditions. The results also confirm the possibility that cyclic seleninate esters could catalyze the further undesired oxidation of disulfides in vivo.
