Disulfides thiol protection

A reasonable mechanism for the iodine oxidation of 5-Trt cysteine peptides is given in Scheme 6. 45 Reaction of iodine with the divalent sulfur atom leads to the iodosulfonium ion 5 which is then transformed to the sulfenyl iodide 6 and the trityl cation. Sulfenyl iodides are also postulated as intermediates in the iodine oxidation of thiols to disulfides. The disulfide bond is then formed by disproportionation of two sulfenyl iodides or by reaction between the electrophilic sulfur atom of R -S-I and the nucleophilic S-atom of a second R -S-Trt molecule. The proposed mechanism suggests that any sulfur substitution (i.e., thiol protecting group) capable of forming a stabilized species on cleavage, such as the trityl cation, can be oxidatively cleaved by iodine. 

A general procedure for the iodine reaction in the solid phase is shown in Scheme 9. Both Boc and Fmoc chemistry can be used to assemble the linear S-protected bis-cysteine peptides and for thiol protection the well-established Acm and Trt groups are usually used. Suitable solvents for the thiol-deprotection/oxidation step by iodine to form the disulfide are CH2C12, DMF, or aqueous AcOH. The final deblocking and cleavage from the resin is carried out under standard conditions. Modification at sensitive amino acid residues caused... 

Ethyl disulfides, to protect thiols, 302 /V-(Ethyldithio) carbamates, to protect amines, 334... 

Iodinolysis in a protic solvent such as methanol easily cleaves the 5-trityl group and oxidises the liberated thiol to a disulfide. The acetamidomethyl group, another common thiol protecting group (see below), cleaves as well but at a much slower rate when non-polar or weakly nucleophilic solvents such as chloroform. 

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... 

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