Acetamidomethyl group

NO2C6H4SCI, AcOH (results in disulfide formation), followed by NaBH4 or HS(CH2)20H or dithioerythritol, quant." 5-Triphenylmethyl, 5-4,4 -di-methoxydiphenylmethyl, and 5-acetamidomethyl groups are also removed by this method. 

Again the stereochemistry of the new-branched thiodisaccharide was assigned on the basis of NOE results displaying a 5% enhancement between the C-acetamidomethyl group and the axial proton (3a-H) at C-3 and no enhancement of die 3e-H signal. The 13C NMR signal of the methylene -CH2-group 8 = 62.4 at C-2 center is characteristic of the link with the quaternary C-2 and also clearly indicates the axial disposition of the new C-2 substituents. 

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. 

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... 

The 5-(acetamidomethyl) group is not necessarily compatible with Nps/tBu chemistry in solution, since it is cleaved by Nps-Cl, formed as an intermediate in the N -deprotection steps with hydrochloric acid.P To bypass this problem, removal of the Nps group can be achieved with alternative reagents such as thiols or phosphines,P or with hydrochloric acid, in this case operating in the presence of 2-methylindole to capture the Nps-Cl.t l... 

Cleavage of the 5-(acetamidomethyl) group is achieved with metal ions such as mercury(II) in aqueous acetic acid or silver(I) in TFA.b In the latter case, the trifluoromethane-sulfonate salt was found to be superior to the trifluoroacetate, and silver tetrafluoroborate is an efficient alternative. While sensitive residues such as Met, Trp, and Tyr are largely unaffected by cleavage with silver(I) salts, mercury(II)-mediated cleavage has been reported to give side reactions at Trp residues, P which can be suppressed by operating in the... 

It is important to note that cleavage of the 5-(acetamidomethyl) group with metal ions, such as thallium(III) trifluoroacetate, or with iodine may lead to alkylation of hydroxy groups,as well as of amide groups,P l via reactive acetamidomethanol intermediates. These side reactions are minimized by the use of glycerol as a scavenger. 

Cleavage of the 5-(Acetamidomethyl) Group with Mercniy(II) Acetate Typical Procednre l °l... 

Removal of an Acetamidomethyl Group from a Uniquely Placed Cysteine Residue... 

The acetamidomethyl group is recommended for thiol protection in, for example, cysteine it is stable to most peptide coupling conditions, but is readily removed by mercuric ion (Scheme 159). An alternative is the4-picolyl group, which affords protection also to the phenolic group of tyrosine cleavage is achieved by electrolytic reduction. 

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]. 

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