Disulfides, to protect thiols

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

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... 

This thiol-disulfide interconversion is a key part of numerous biological processes. WeTJ see in Chapter 26, for instance, that disulfide formation is involved in defining the structure and three-dimensional conformations of proteins, where disulfide "bridges" often form cross-links between q steine amino acid units in the protein chains. Disulfide formation is also involved in the process by which cells protect themselves from oxidative degradation. A cellular component called glutathione removes potentially harmful oxidants and is itself oxidized to glutathione disulfide in the process. Reduction back to the thiol requires the coenzyme flavin adenine dinucleotide (reduced), abbreviated FADH2. 

This reaction also protects proteins with cysteine residues from becoming oxidized to the disulfide since the GSH can be used to reduce the protein disulfide back to the thiol form ... 

In this approach an orthogonal S-protection consisting of the acid-labile Mob and the Acm group was selected. Free thiol peptides were prepared by acid treatment of the precursors and activated with di(2-pyridyl) disulfide to afford the 5-SPy derivatives which served for the preparation of the two heterodimers 60 and 62 via thiolysis with a second cysteine peptide. In both heterodimers 60 and 62 the Acm group was cleaved with silver(I) trifluoroacetate in TFA to generate the mercaptide. Following gel filtration in acidic media the free thiol from 62 was activated as the S-SPy derivative 63 and subsequent thiolysis with the second heterodimer 61 in the free thiol form produced the heterotetramer 64. 

As in the case of poly(U), which has been studied as a model system in some detail (Chap. 11.2), there is a relationship of the rate of protection of DNA by thiols and disulfides and the charge of the sulfur compound due to ion condensation (for evidence of this phenomenon, see Smoluk et al. 1988b). As has been measured by following the protection of DNA irradiated in aqueous solution against base release (Zheng et al. 1988), G(base release) follows the equation G0/Gp = 1 + 3[RSH]. The data, compiled in Table 12.16, have been interpreted in terms of electrostatic interaction of thiols of the thiols/disulfides with DNA leading to higher concentrations of cations with respect to neutral thiols/disulfides... 

Inspection of the literature identified work by Hiskey and Tucker11 who reported the use of iodine to cleave a THP-protected thiol in 1962. Even earlier work by Ratner and Clarke in 1937 demonstrated that thiazolidines can also be cleaved using iodine.12 Both of these reactions give rise to disulfides (Fig. 3). It is interesting to note that Hiskey and Tucker comment that their approach was suggested by the earlier work of Bonner, 13 who in 1948 demonstrated the conversion of acetylated... 

During a synthesis of the antibiotic Micacocidin, a p-methoxybenzyl group was used to protect the thiol function in intermediate 8.1 [Scheme 5.8].22 The 5-p-methoxybenzyl group was cleaved in two steps by first reacting 8.1 with 3-nitro-2-pyridinesulfenyl chloride (83) to give the disulfide intermediate 83 which was then treated with tributylphosphine in aqueous acetone to afford the thiol 8.4 in 69% overall yield for the two steps 2324... 

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