Disulfides displacement reactions

The preparation of a trisulfide bridge between two different linear peptides is outlined in Scheme 3. In a first step, the free thiol of one peptide forms an activated mixed disulfide by reaction with TV,A1 -1hiobisphthalimide, and upon the subsequent addition of the second cysteine peptide, nucleophilic displacement of the phthalimide moiety by the free thiol yields the desired interchain trisulfide bridged peptide 3.1 3 Homodimeric analogues, e.g. 4, are prepared similarly.[13]... 

In the first step of the conversion catalyzed by pyruvate decarboxylase, a carbon atom from thiamine pyrophosphate adds to the carbonyl carbon of pyruvate. Decarboxylation produces the key reactive intermediate, hydroxyethyl thiamine pyrophosphate (HETPP). As shown in figure 13.5, the ionized ylid form of HETPP is resonance-stabilized by the existence of a form without charge separation. The next enzyme, dihydrolipoyltransacetylase, catalyzes the transfer of the two-carbon moiety to lipoic acid. A nucleophilic attack by HETPP on the sulfur atom attached to carbon 8 of oxidized lipoic acid displaces the electrons of the disulfide bond to the sulfur atom attached to carbon 6. The sulfur then picks up a proton from the environment as shown in figure 13.5. This simple displacement reaction is also an oxidation-reduction reaction, in which the attacking carbon atom is oxidized from the aldehyde level in HETPP to the carboxyl level in the lipoic acid derivative. The oxidized (disulfide) form of lipoic acid is converted to the reduced (mer-capto) form. The fact that the two-carbon moiety has become an acyl group is shown more clearly after dissocia-... 

Further transfer of the acyl group to coenzyme A is catalyzed by the same enzyme. This displacement reaction produces reduced lipoic acid. A third enzyme, dihydrolipoyl dehydrogenase, catalyzes oxidation of this product back to the disulfide form. The electrons lost in that oxidation are transferred first to an enzyme-bound flavin (not shown in the figure) and then to NAD +. ... 

Berdnikov VM, Bazhin NM, Fedorov VK, Polyakov OV (1972) Isomerization of the ethoxyl radical to the a-hydroxyethyl radical in aqueous solution. Kinet Catal (EngITransI) 13 986-987 Bonifacic M, Asmus K-D (1984) Adduct formation and absolute rate constants in the displacement reaction of thiyl radicals with disulfides. J Phys Chem 88 6286-6290 Bonifacic M, Mockel H, Bahnemann D, Asmus K-D (1975a) Formation of positive ions and other primary species in the oxidation of sulphides by hydroxyl radicals. J Chem Soc Perkin Trans 2 675-685... 

Hummel and Hindsgaulfel developed a solid-phase synthesis of thio-oligosac-charides exemplified by the synthesis of the trisaccharide 31,5 [Scheme 531], which features the use of a disulfide to protect an anomeric thiol. The method exploits a highly reactive sugar thiolate 31,1 devoid of protecting groups as the nucleophile in a displacement reaction on triflate-activated glycoside 31,2 The... 

Other miscellaneous 1-thio derivatives convertible to thioaldoses are glycosyl thioimidocarbonates and diglycosyl disulfides [1], Their s)uitheses are similar to the ones described above, i. e., displacement reactions of an acylated glycopyranosyl halide with a thionucleophile, an... 

The major part of the second section is devoted to thiyl radicals. This species has long been viewed as relatively uninteresting with respect to its chemistry since its only fate was thought to be dimerization to the respective disulfide. Like the aminyl radicals, thiyl radicals can engage in a large variety of reactions. Radiation chemical studies have identified and quantified reactions in which thiyl radicals act as hydrogen abstraction agent, showed their involvement in reversible addition and displacement reactions and, last but not... 

This reaction actually proceeds through two steps, each a nucleophilic displacement reaction by mercaptide ion on the symmetrical disulfide (I in Equation B), and then on the mixed disulfide (V in Equation C). 

Salts of hydrogen cyanide have also been found to be capable of nucleophilic cleavage of the disulfide bond in keratin fibers [72]. In addition, nearly quantitative conversion of cystinyl residues to lanthionyl residues can be achieved in this reaction [73]. The most plausible mechanism is given in Equations G and H [65]. This mechanism consists of two nucleophilic displacement reactions the first by cyanide on sulfur and the second by mercaptide ion on carbon. The following mechanism is consistent with the observed formation of thioether from the reaction of N-(mercaptomethyl)polyhexamethyleneadipamide disulfide (XV) with cyanide, but not with alkali [65]. 

A novel displacement reaction in permanent-waving involves treating reduced hair with polyoxyethylene esters of thioglycolic acid (MW 550-750) described recently by Salce et al. [3]. These esters are reported to bind to the fibers by displacement of reduced disulfide in hair on the ester linkage of the additive resulting in the formation of mixed disulfides, producing more hydrophobic hair fibers and improvement in the curl relaxation due to the increased hydrophobicity. 

Dimethyl sulfoxide is a favored solvent for displacement reactions in synthetic chemistry. The rates of reaction in DMSO are many times faster than in an alcohol or aqueous medium [6]. Dimethyl sulfoxide is the solvent of choice in reactions where proton (hydrogen atom) removal is the rate determining step. Reactions of this type include olefin isomerizations and reactions where an elimination process produces an olefin. Another application that uses DMSO is its use as an extraction solvent to separate olefins from saturated paraffins [7]. Several binary and ternary solvent systems containing DMSO and an amine (e.g., methylamine), sulfur trioxide, carbon disulfide/ amine, or sulfur trioxide/ammonia are used to dissolve cellulose, and act as spinning baths for the production of cellulose fibers [8,9]. Organic fungicides, insecticides, and herbicides are readily soluble in DMSO. Dimethyl sulfoxide is used to remove polymer residues from polymerization reactors. 

Milder oxidation, using halogens (F or Br2) in base, is a general source of disulfides. This reaction probably involves a sequence of displacement reactions (Fig. 16.77). 

Displacement reactions with disulfides are a second major pathway to generate thiyl radicals. Formally, this constitutes a one-electron reduction of the disulfide. Homolytic sulfur-sulfur bond breakage by carbon-centered or phosphite radicals, for example, has been shown to lead to sulfides with mixed substitution and thiophosphates, respectively [17, 18], reactions (5) and (6) ... 

In organic chemistry, particularly synthesis, all these displacement reactions with disulfides have for the most part served as a means of obtaining the respective molecular products, and the focus has been much less on the study of the thiyl free radicals per se. Radiation chemical investigations on these processes have, however, revealed many interesting details of the respective mechanisms and, as such, supported a number of suggestions and conclusions made in... 

The acidic character of siUca is shown by its reaction with a large number of basic oxides to form siUcates. The phase relations of numerous oxide systems involving siUca have been summarized (23). Reactions of siUca at elevated temperatures with alkaU and alkaline-earth carbonates result in the displacement of the more volatile acid, CO2, and the formation of the corresponding siUcates. Similar reactions occur with a number of nitrates and sulfates. Sihca at high temperature in the presence of sulfides gives thiosiUcates or siUcon disulfide, SiS2. 

---