Cysteine protecting groups

Historically, the first important cysteine protecting group was the 5-benzyl group, developed by du Vigneaud etal. and used in the classical synthesis of oxytocin,t as well as in the syntheses of a number of cysteine-containing peptides in the first years of solid-phase synthetic methodology.P l This 5-Bzl protection is nowadays used infrequently due to the fact that its removal involves harsh conditions, e.g. sodium in liquid ammoniat or anhydrous hydrogen fluoride at 20°C,t conditions which may lead to side reactions such as elimination... 

Deblocking cysteine protecting groups. The common S-protecting groups can be cleaved by reaction with 2-nitrophenylsulfenyl chloride in acetic acid followed by reduction of the S-(2-nitrophenylsulfenyl)cysteine residues (equation I). 

Table 1. Cysteine protecting groups compatible with Fmoc/lBu solid-phase peptide synthesis ... 

Mixed disulphides are usuaUy precluded as cysteine protecting groups in the Fmoc/rBu strategy, because such functions are relatively unstable on exposure to piperidine. However, the 5-fcrf-butylmercapto (S -SrBu) group (42) is sufficiently hindered to be compatible its removal is achieved by treatment with either p-mercaptoethanol, dithiothreitol (DTT), tri- -butylphosphine (BU3P), or other reducing agents (5,6). 

Kemp DS, Carey RI (1993) Synthesis of a 39-peptide and a 25-peptide by thiol capture ligations observation of a 40-fold rate acceleration of the intramolecular 0,N-acyl-transfer reaction between peptide fragments bearing only cysteine protective group. J Org Chem... 

When cysteine reacts with an alkyl or aiyl chloroformate, both the —SH and —NH groups are protected as a thiocarbonate and as a carbamate, respectively. Selective or simultaneous removal of the protective groups is possible. 

Na/NH3, -30°, 3 min, 1(X)% yield. This protective group is stable to acidic hydrolysis (4.5 N HBr/HOAc 1 N HCV, CF3CO2H, reflux). There is no evidence of S N acyl migration in 5-(A-ethylcarbamates) (RS = cysteinyl). Oxidation of 5-(A-ethylcarbamoyl)cysteine with performic acid yields cysteic acid. ... 

Nakajima and Okawa prepared cysteine (250 Scheme 3.92) by treating aziridine 127a with dry H2S gas in the presence of a catalytic amount of BF3 Et20 [141]. The resulting thiol 248 was then oxidized with iodine to afford disulfide 249 in 70% overall yield. Removal of the Cbz protecting group afforded cysteine (250). 

In a comparison between various reactive dyes for wool and several commercially available colourless fibre-protecting agents, it was shown that reactive dyes in medium and full depths are significantly more effective. Reaction readily occurs between typical reactive dyes and the cysteine thiol groups (Scheme 7.47) released when the cystine disulphide bonds are hydrolysed under dyeing conditions. Such reactions inhibit thiol-disulphide... 

E Wtinsch, R Spangenburg. A new S-protecting group for cysteine, (in German) (5-terf-butyl) in E Scoffone, ed. Peptides 1969. Proceedings of the 10th European Peptide Symposium, North-Holland, Amsterdam, 1971, pp 30-34. 

DF Veber, JD Milkouski, RG Denkewalter, R Hirschmann. The synthesis of peptides in aqueous solution. IV. A novel protecting group for cysteine. (S-acetamidomethyl) Tetrahedron Lett 3057, 1968. 

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