Protection of thiol groups

Ironically, a very suitable reagent for protecting the thiol group had been described in 1905 but was not applied to peptide synthesis until 1972 (Veber et al., 1972), a salutary reminder that a lot of useful chemistry may be lurking in the old 

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At pH 4-5, the reaction is selective for protection of thiol groups in the presence of oc- or e-amino groups. 

Protection of thiol groups is a substantive issue in peptide chemistry where protection and deprotection of cysteine and the attendant problem of disulfide bond formation is a major challenge. An authoritative review of the subject by Moroder and co-workers can be found in Synthesis of Peptides and Peptidomi-metics (Houben-Weyl), Vol E22a. ... 

Protection of thiol groups. Under catalysis by a base (N-methylmorpholine) the reagent reacts with cysteine groups ... 

Protection of thiol groups. Japanese chemists have used the 2-picolyl 1-oxide group for protection of thiols. The protective group is removable by acetic... 

The base-catalyzed reaction of thiothreitol with methyl dithiobenzoate selectively protects a thiol group as an 5-thiobenzoyl derivative in the presence of a hydroxyl group.-... 

The role of GSH in cellular protection (see below) means that if depleted of GSH, the cell is more vulnerable to toxic compounds. However, GSH is compartmentalized, and this compartmentalization exerts an influence on the relationship between GSH depletion or oxidation and injury. The loss of reduced GSH from the cell leaves other thiol groups, such as those in critical proteins, vulnerable to attack with subsequent oxidation, cross-linking, and formation of mixed disulfides or covalent adducts. The sulfydryl groups of proteins seem to be the most susceptible nucleophilic targets for attack, as shown by studies with paracetamol (see chap. 7), and are often crucial to the function of enzymes. Consequently, modification of thiol groups of enzyme proteins, such as by mercury and other heavy metals, often leads to inhibition of the enzyme function. Such enzymes may have critical endogenous roles such as the regulation of ion concentrations, active transport, or mitochondrial metabolism. There is... 

Protection of thiols. The r-butyl group has been of limited service for protection of thiols because removal has involved rather drastic treatment with liquid HF. r-Butyl thioethers can be cleaved by treatment with o-nitrobenzene-sulfenyl chloride in acetic acid at 25° to give S-o-nitrophenylsulfeny derivatives. These products are reduced to thiols with NaBH4, HSCH2C02H, or HOCH2CH2SH. 

A very convenient method has been devised [40] for the conversion of thiols to ethyldithio derivatives as a routine procedure for protection of thiol-substituted organic acids. It uses a DMAP-catalysed exchange of the ethylthio group between a thiol and ethyl 2-pyridyl disulfide, prepared from the commercially available 2,2 -dithiobispyridine. Filtration through a macroporous sulfonic acidic resin and evaporation of the solvent yielded the disulfide directly. 

A number of other groups can be used for the protection of thiols benzyl thioethers of amino acids and peptides have been cleaved electrochemically at a platinum cathode in liquid ammonia [121], at mercury in MeOH-TMACl [122], and in DMF [123,124], and the trityl group has been used to protect cysteine cysteine was recovered in 90% yield after reduction in DMF [124]. The 4-pyridylmethyl [125,126] and diphenyl-4-pyridylmethyl groups can be cleaved in acid solution [124] at a mercury cathode. 

Thiol esters are reduced at less negative potentials than carboxylic esters and can be cleaved in protic (e.g., methanol) [141] or aprotic [123, 142] media. Aroyl and benzylox-ycarbonyl groups may thus be used for protection of sulfhydryl groups in MeCN the radical anion of an arylthioic 5 -ester is usually cleaved to alkylthiolate and aryl radical if it is relatively stable (minutes) it reacts eventually with oxygen with formation of an arylcarboxylate [43]. 

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