Kenichi Akaji

Syntheses of Natriuretic Peptides Using a New S-Protecting Group, S-Trimethylacetamidomethyl (Tacm) Group

Protection of the thiol function of cysteine is required during peptide synthesis (Hiskey, 1981). One of the widely used protecting groups is S-acetamidomethyl (Acm), which is stable in acidic conditions such as trifluoroacetic acid (TFA) and hydrogen fluoride (HF) but can be removed with Hg(OAc)2 in TFA (Veber et al, 1972) or I2 in aqueous AcOH (Kamber et al., 1980; Sieber et al., 1980). However, during the preparation of Cys(Acm), thiazolidine-2-carboxylic acid was formed as a by-product. The activation of Boc-Cys(Acm)-OH using the N,N’-dicyclohexylcarbodiimide (DCC) and 1-hydroxy-benzotriazole (HOBt) method was also accompanied by a side reaction. When the S-benzamido-methyl (Bam) group (Chakravaty and Olsen, 1978) is used, these side reactions are greatly reduced, but it is slightly unstable during HF cleavage condition (0°C, 1 h) and alkaline conditions. We describe here the preparation and characterization of a new S-protecting group, the S-trimethylacetamidomethyl (Tacm) group, and its application to the syntheses of natriuretic peptides.