S-Acetamidomethyl group

S-Acetamidomethyl groups are introduced by reaction of the thiol with l-(acet-amidomethyl)-benzotriazole69 or N-( hydroxy me thyl)acetamide under acidic conditions.62 70 The latter procedure is also used to introduce the S-phenylacetami-domethyl (Phacm) group [Scheme 5.37].71 Thus, the Phacm group can be introduced onto L-cysteine by reaction of yV-(hydroxymethyl)phenylacetamide 37 1 with cysteine hydrochloride in the presence of trifluoromethanesulfonic add. The crude intermediate is then treated with di-/erf-butyl dicarbonate (or... 

NO2C6H4SCI, AcOH (results in disulfide formation), followed by NaBHi or HS(CH2)20H or dithioerythritol, quant. 5-Triphenyhnethyl, 5 -4,4-dimethoxy-diphenylmethyl, and S-acetamidomethyl groups are also removed by this method. 

A related S-protective group of considerable utility that was developed for the preparation of cysteine peptides in aqueous medium is the S-acetamidomethyl group [134, 184]. 

Protection of —SH Groups.—Although silylation of functional groups has become a valuable means of transient protection, and can be applied to thiols (RSH -> RSSiMea using hexamethyldisilazane and imidazole), " S-protection problems are mostly those of cysteine, and must be solved so that peptide-coupling and selective de-protection techniques can be applied. The S-acetamidomethyl group " has been put to use in protection of the... 

Thiol Protectton with the AcETAMiDOMErHYL Group S-Acetamidomethyl-l-... 

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. 

Different protecting groups (S-Trityl, S-Acetamidomethyl...) have been introduced on the cysteine side chains to optimise the reaction conditions of disulfide bridge formation. The conditions developed by Kamber and his group have been used to make the disulfide bridge (ref. 5). The best results have been obtained when we use S trityl on the L-cysteine and S-acetamidomethyl on the 7 cysteine in N,N-dimethylformamide in the presence of an excess of iodine (4 equivalents). The excess of iodine is eliminated with ascorbic acid. The final peptide is isolated by precipitation with water. 

Mercuric acetate (formic acid Acetamidomethyl as S-protective group... 

The Npys group can be. cleaved reductively with BU3P, H2O or mercaptoethanol. It is stable to CF3COOH (24 h), 4 M HCl/dioxane (24 h), and HF (1 h). The related reagent, 2-pyridinesulfenyl chloride, has also been proposed as a useful reagent for the deprotection of the 5-trityl, 5-diphenylmethyl, 5-acetamidomethyl, 5-/-butyl, and S-r-butylsulfenyl groups, but this reagent is very susceptible to hydrolysis. ... 

Triphenylmethylcysteine is readily oxidized by iodine (MeOH, 25°) to cystine. The 5-triphenylmethylcysteine group can be selectively cleaved in the presence of a -Cys(Acm)- group (Acm = acetamidomethyl). 5-Benzyl and S -Fbutyl thioethers are stable to the action of iodine. 

PS—Cl deprotects cysteine residues protected with trityl, diphenylmethyl, acetamidomethyl, f-butyl, and t-butylsulfenyl groups a mixed disulfide, CyS—S—PS, is obtained, which can form a disulfide with another SH group. Thus it can also be used to form disulfide bonds between two cysteine-containing peptides. ... 

---