The 2,4,6-trimethoxybenzyl (Tmob) group is very suitable for temporary protection of the aminosulfonyl group of S-cysteine-and homo-S-cysteinesulfonamides. Both the introduction and removal of the Tmob-protecting group can be achieved in high yields. 2-Aminoethyl derivatization of the aminosulfonyl group of S-cysteine-and homo-S-cysteinesulfonamides has been carried out, and various derivatives useful for peptide synthesis with Z, Boc and Fmoc as N,-protecting groups have been prepared. In all cases, a racemic mixture of Scysteine-or homo-S-cysteinesulfonic acid has been used and subsequent enantiomer resolution has been achieved by treatment with Bacillus subtilis alkaline protease.Since a long time due to its structural similarity to asparagine, S-cysteinesulfonamide was suspected to have the ability to act as antagonist [']. Hence, several methods for the synthetic preparation of this sulfonamide have been reported by different authors, all based on oxidative chlorination of the disulfide bond in the cystine molecule followed by replacement of the chlorine atom in the sulfochloride by an amino g r o~p [~-~] .A common shortcoming of these methods is the high instability of the intermediate sulfochloride. The latter undergoes fast hydrolysis which is the reason for the low yields of the sulfonamide. Therefore, we began studies on S-cysteinesulfonamide derivatives and particular attention was payed to the stability of the respective sulfochloride intermediates. Our experiments showed that stable cysteine sulfochloride derivatives are obtained only if both the amino and the carboxy groups are blocked [6]. A convenient combination of protecting groups proved to be the N,-benzyloxycarbonyl and benzyl or ethyl ester group. For cysteine sulfochloride-containing peptides it was observed that stability is strongly dependent on the molecular mass of the peptide. If it is higher than 1000, the half-life is very shortr71.The investigation of the biological activity of S-cysteinesulfonamide derivatives with modified aminosulfonyl group[*] as well as S-cysteinesulfonamide-containing peptided9] demonstrated that the interest in those products is fully justified [lO]. In several cases, the peptides were obtained in significantly reduced yields due to side reactions of the unprotected aminosulfonyl group[' ' 1. Therefore, we had to find a suitable group for temporary protection of this function that would allow its utilization in peptide synthesis, including the solid-phase method. Our efforts were also directed to the preparation of suitably protected Scysteinesulfonamides (3-[(2,4,6-trimethoxybenzyl)aminosulfonyllalanine) and homo-S-cysteinesulfonamides (2-amino-4-[(2,4,6-trimethoxybenzyl)aminosulfonyl]butyric acid) to be used in solid-phase or conventional synthesis of biologically active compounds.The starting compounds were N,-benzyloxycarbonyl-protected sulfochlorides of S-cysteinesulfoni~[~-~~'~] and homo-S-cysteinesulfonic acid[l31 esters prepared by methods described in the literature. The aminosulfonyl group was prot...