Study of the alkylation propensity of cations generated by acidolytic cleavage of protecting groups in Boc chemistry

The alkylation of cysteine residue by different classes of carbonium ions, derived from the cleavage of side chain protective groups in anhydrous HF, was investigated; It was found that side chain protection as beta-2,4-dimet hylpent-3-yl ester (Dmp) or 2,4-dimethylpent-3-yloxycarbonyl (Doc) groups r esulted in more than seven-fold lower level of alkylated byproducts. This m akes Dmp and Doc protection of amino acid side chain during solid phase syn thesis particularly valuable in the synthesis of peptides containing cystei ne residues or other functional groups prone to alkylation by carbonium ion s.