S-Trityl group

The syn geometry of 1 allows three S-trityl groups of three different molecules to interdigitate and the carboxylic groups of 1 to dimerize through two strong... 

The role of methanol is quite important ih this reaction it acts as the acceptor of the trityl group. In a similar fashion ethylmercaptane, used in considerable excess, facilitates the acidolytic cleavage of the S-trityl group and prevents realkylation of the regenerated sulfhydryl group ... 

After removal of the S-Trityl groups by silver nitrate (Zervas, 1962), the free thiol groups were oxidized by diiodoethane (Weygand, 1962). Bty releasing the peptides obtained from the polymer by treatment with HBr in trifluoroacetic acid followed by purification on Dowex 50, E. Bondi of our department obtained an 80% overall yield of H2N Cys-Cys-AlaOH. 

Finally, it has been noted that the attempted detritylation of open-chain unsymmetrical disulphides containing S-trityl groups using silver nitrate in pyridine led to extensive decomposition and neither the silver mercaptide nor thiol (after treatment of the reaction mixture with hydrogen sulphide) could be isolated [94]. Thus there is some question as to whether peptides containing preformed cystine residues and S-trityl or S-benz-hydryl cysteine can be deblocked with heavy metals without causing cleavage of the disulphide bond. 

Kamber [92] reports that in contrast to S-benzhydryl phenyl thioether [79], S-benzhydryl-L-cysteine derivatives are oxidatively cleaved to the extent of about 20% by iodine in methanol. It is likely, however, that the S-trityl group can be removed with iodine without disturbing S-benzhydryl groups in... 

The selective removal of the S-benzoyl group in the presence of other S-protected cysteine residues was studied by Zervas et al. [88] who prepared the insulin fragment, (66). The S-benzoyl groups were removed with 0.55N-sodium methoxide in methanol-DMF. In a related study [89] the S-benzoyl group was removed in the presence of the S-benzhydryl and S-trityl groups (18c, d). 

The conversion of 3 to 8 is summarized in Scheme 2. The trityl group (too large and too acid sensitive for the ensuing steps) was removed from N, and both N s were protected by Cbz (benzyloxycarbonyl) groups. Protection of the tertiary OH specifically as the robust TBS (f-butyldimethylsilyl) group was found to be necessary for the sequence involving the electrophilic aromatic substitution step, 5 to 6, and the Stille coupling steps (6 + 7 —> 8). 

For a review in which the use of various trityl groups in nucleotide synthesis is discussed in the context of the phosphoramididite approach, see S. L. Beaucage and R. P. Iyer, Tetrahedron, 48, 2223 (1992). 

An S-4-methoxybenzyl thioether is stable to HBr/AcOH1 and I2/MeOH.2 The latter reagent cleaves S-trityl and S-diphenylmethyl groups. 

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