RhCl3-catalyzed disulfide exchange reaction using water solvent in homogeneous and heterogeneous systems

RhCl₃ catalyzed the alkylthio exchange reaction of hydrophilic disulfides in water under homogeneous conditions, and equilibrium was attained in several hours. The reaction was applied to the exchange of unprotected glutathione disulfide. The reaction of dimethyl disulfide and hydrophilic disulfides under heterogeneous conditions also proceeded effectively. The mechanism turned out to be dependent on the water solubility of the substrates: The reaction of bis(3-hydroxypropyl) disulfide took place in the dimethyl disulfide phase, whereas the reaction of bis(6-aminohexyl) disulfide dihydrochloride proceeded in the water phase.     

Oxidative Coupling of Thiols to Disulfides with Ti(IV) in the Presence of NaI under Air Atmosphere

Ti(IV) as TiCl₃(O₃SCF₃) and TiO(O₂CCF₃)₂ are used as efficient catalysts for oxidative coupling of aliphatic, aromatic and heteroaromatic thiols to their disulfides in the presence of NaI under air atmosphere.     

Silver(I) catalyzed oxidation of thiocarboxylic acids into the corresponding disulfides and synthesis of some new Ag(I) complexes of thiophene-2-thiocarboxylate

Aromatic thiocarboxylic acids in presence of a base on treatment with silver nitrate under ambient conditions were oxidized to the corresponding disulfides. The reactions were found to be catalyzed by Ag⁺ ions. The catalytic oxidation is paralleled by the Ag(SCOAr) complex formation reaction which could be considerably subsided by adjustment of the reaction conditions. Attempts to use [Ag(PPh₃)₂]⁺ or [Ag(PPh₃)]⁺ ion as the catalyst were unsuccessful as these resulted in the formation of the corresponding thiocarboxylate complexes. The products, ArCOSSCOAr (1, 2), [Ag(SCOAr)(PPh₃)₂] (3, 4) and [Ag(SCOAr)(PPh₃)]₄ (5) (Ar = C₆H₅, C₄H₃S) were characterized by single crystal X-ray analysis. Compounds 3 and 4 are monomeric while 5 is a cyclic tetramer in the crystalline phase.     

Fe(HSO4)3 and Fe(HSO4)3/DMSO as Efficient,Heterogeneous, and Reusable Catalyst Systems for the Oxidative Coupling of Thiols

Fe(HSO₄)₃ has been used as a heterogeneous, efficient, and recyclable catalyst in ethanol for the selective oxidation of thiols to their corresponding disulfides. The same results were obtained under identical conditions using catalytic amounts of Fe(HSO₄)₃ in the presence of DMSO. Different types of aliphatic, aromatic, and heteroaromatic thiols have been used in the reaction, and in all cases the products were obtained in good to excellent yields.     

Simple and efficient copper-catalyzed S-arylation of diaryl disulfides with triarylbismuthanes under aerobic conditions

Novel and simple copper-catalyzed C(aryl)-S bond formation of diaryl disulfides with bismuth reagents is described. Reactions of diaryl disulfides with triarylbismuthanes in the presence of CuOAc (10 mol %) and 1,10-phenanthroline (10 mol %) under aerobic conditions led to the formation of unsymmetrical diaryl sulfides in satisfactory yields. The reaction is atom-economic and all three aryl groups of the triarylbismuthanes and both sulfanyl groups of the diaryl disulfides could be transferred to the coupling products.     

Reactions of thiols and organic disulfides with iron and its oxides

The influence of O₂ and H₂O on the formation of iron dithiolates (IDTs) by the reactions of thiols and organic disulfides with the iron powder was studied under the static (without mechanical activation of the reaction) and dynamic (with mechanical activation of the reaction) conditions. Under the static conditions in the absence of O₂ or H₂O, only BnSH and PhSH give IDTs, whereas DdSH (Dd is dodecyl) produces IDTs in the presence of O₂ or H₂O. For the mechanical activation of the reactions of organic disulfides with the iron powder, the formation of IDTs is possible if the reaction mixture contains H₂O. On the interaction with iron oxides excess thiols are oxidized to organic disulfides and also afford IDTs. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1383–1386, August, 2006.     

Oxetane Grafts Installed Site‐Selectively on Native Disulfides to Enhance Protein Stability and Activity In Vivo

A four‐membered oxygen ring (oxetane) can be readily grafted into native peptides and proteins through site‐selective bis‐alkylation of cysteine residues present as disulfides under mild and biocompatible conditions. The selective installation of the oxetane graft enhances stability and activity, as demonstrated for a range of biologically relevant cyclic peptides, including somatostatin, proteins, and antibodies, such as a Fab arm of the antibody Herceptin and a designed antibody DesAb‐Aβ against the human Amyloid‐β peptide. Oxetane grafting of the genetically detoxified diphtheria toxin CRM₁₉₇ improves significantly the immunogenicity of this protein in mice, which illustrates the general utility of this strategy to modulate the stability and biological activity of therapeutic proteins containing disulfides in their structures.     

Hydrothiolation of terminal alkynes with diaryl disulfides and diphenyl diselenide: selective synthesis of (Z)-1-alkenyl sulfides and selenides

A simple, stereoselective and efficient method for the hydrothiolation of terminal alkynes with diaryl disulfides and diphenyl diselenide has been developed. In the presence of CuI, rongalite, and Cs₂CO₃, a variety of disulfides underwent the reaction of terminal alkynes stereoselectively to afford the corresponding (Z)-1-alkenyl sulfides in moderate to excellent yields. It is noteworthy that hydroselenations of 1,2-diphenyldiselane with alkynes are also conducted smoothly to afford (Z)-1-alkenyl selenides in good yields under the standard conditions.     

Oxidative transformation of thiols to disulfides promoted by activated carbon-air system

Efficient oxidative transformation of thiols to disulfides took place in the presence of activated carbon under an oxygen (or air) atmosphere. The present oxidation method is available not only for a variety of thiols such as simple aromatic and aliphatic thiols but also for 3,4-dihydropyrimidin-2(1H)-thiones and N-Boc-l-cysteine.     

Metal-catalyzed phosphinyl ester forming reaction of alcohols and phenols with diphosphine disulfides and a dioxide

Transition metal complexes catalyzed the dialkylphosphinothioation reaction of alcohols and phenols with tetraalkyldiphosphine disulfides in high yields. Phenols were reacted in the presence of RhH(PPh₃)₄ and 1,2-bis(dimethylphosphino)ethane under THF reflux, and alcohols with Pd(OAc)₂ and 1,2-bis(diphenylphosphino)benzene under chlorobenzene reflux. Primary alcohols reacted faster than secondary alcohols under these conditions, and protected tyrosine and serine were phosphinothioated with minimal racemization. Tetraphenyldiphosphine dioxide also underwent the P-O bond formation reaction.     

Clean and fast oxidative transformation of thiols to disulfides under solvent-free conditions

We present here a fast, solvent-free synthesis of symmetrical disulfides using solid supported catalyst (Al₂O₃/KF). The reaction was performed at room temperature, by gentle heating or under MW irradiation. This efficient and improved method is general for liquid thiols, affording the disulfides in good to excellent yields. The catalytic system can be re-used two times without previous treatment and with comparable activity.     

Rhodium-catalyzed thiophosphinylation and phosphinylation reactions of disulfides and diselenides

Alkyl and aryl dithiophosphinates were synthesized by the reaction of disulfides with biphosphine disulfides in the presence of RhH(PPh₃)₄ and 1,2-diphenylphosphinoethane (dppe). The catalyst also promoted synthesis of thiophosphinates and selenothiophosphinates from disulfides and diselenides.     

General, fast, and high yield oxidation of thiols and disulfides to sulfonic and sulfinic acids using HOF·CH3CN

Thiols and disulfides are oxidized to the corresponding sulfonic and sulfinic acids using HOF·CH₃CN. This oxidation is suitable for a variety of thiols and disulfides and proceeds under mild conditions, in short reaction times and with high yields.     

Perfluoroalkylation of 2-Thiopyrimidine Derivatives

The method of perfluoroalkylation of heterocyclic thiols and disulfides by thermolytic reaction with xenon(II) bisperfluoroalkylcarboxylates has been extended to sulfur-containing pyrimidines, including 2-mercaptopyrimidines, symmetrical disulfides, and S-trifluoroacetyl derivatives obtained from the corresponding thiols. The main reaction products are 2-SC_nF_2n+1 (n = 1, 2)-substituted pyrimidines. Their formation proceeds only via disulfides into which the initial thiols and S-trifluoroacetyl derivatives are converted in the reaction medium. Side reactions occurred in the case of trifluoromethylation linked with the perfluoroalkylation of the pyrimidine nucleus at the free 5 position (in the case of the 4,6-dimethyl derivative), or at position 4 or 4 and 5 (for unsubstituted pyrimidine). In addition, the introduction of the CF₃ group at one of the methyl substituents was confirmed by the formation of CH₂CF₃ fragment.     

Oxidation of disulfides with Selectfluor™: concise syntheses of thiosulfonates and sulfonyl fluorides

The reaction of aromatic or benzylic disulfides with 2.5 equiv of Selectfluor™ in acetonitrile/water (10:1) at room temperature efficiently produced the corresponding thiosulfonates. On the other hand, the reaction of disulfides with 6.5 equiv of Selectfluor™ in refluxing acetonitrile/water (10:1) provided sulfonyl fluoride in high yields.     

A new reagent for the efficient synthesis of disulfides from alkyl halides

Benzyltriethylammonium tetracosathioheptamolybdate [(C₆H₅CH₂N(Et)₃)₆Mo₇S₂₄] has been found to be a superior sulfur transfer reagent for the conversion of alkyl halides to the corresponding disulfides in excellent yields under very mild reaction conditions.     

A New Application of N,N ′-dibromo-N,N ′–1,2-ethanediylbis(p-toluenesulfonamide) as Selective and Efficient Reagent for the Oxidation of Various Thiols to Disulfides

ABSTRACT

An efficient method for oxidation of thiol to their corresponding disulfides in high yields with N, N^′-Dibromo-N,N^′–1,2-ethanediyl bis (p-toluensulphonamide) in dichloromethane at room temperature is described.     

Visible-light-mediated facile synthesis of disulfides using reusable TiO2/MoS2 nanocomposite photocatalyst

A nontoxic and inexpensive TiO₂/MoS₂ nanocomposite was prepared and employed as an efficient photocatalyst for the synthesis of symmetrical disulfides under visible light irradiation at room temperature. Both aryl and alkyl thiols survived the reaction conditions, affording the corresponding disulfides in good to excellent yields. The photocatalyst could be easily recovered by simple centrifugation and filtration and reused several times without significant loss in its activity.     

Disulfide Click Reaction for Stapling of S-terminal Peptides

A disulfide click strategy is disclosed for stapling to enhance the metabolic stability and cellular permeability of therapeutic peptides. A 17-membered library of stapling reagents with adjustable lengths and angles was established for rapid double/triple click reactions, bridging S-terminal peptides from 3 to 18 amino acid residues to provide 18- to 48-membered macrocyclic peptides under biocompatible conditions. The constrained peptides exhibited enhanced anti-HCT-116 activity with a locked α-helical conformation (IC₅₀=6.81 μM vs. biological incompetence for acyclic linear peptides), which could be unstapled for rehabilitation of the native peptides under the assistance of tris(2-carboxyethyl)phosphine (TCEP). This protocol assembles linear peptides into cyclic peptides controllably to retain the diverse three-dimensional conformations, enabling their cellular uptake followed by release of the disulfides for peptide delivery.