Studies of Unnatural Amino Acids and Their Peptides. II. The Syntheses of Dl -β-(4-Thiazolyl)-α-alanine and Its Peptides

Dl-β-(4-Thiazolyl)-α-alanine has been synthesized in a good yield by the condensation of 4-thiazolylmethyl chloride and diethyl acetamidomalonate, and by the subsequent hydrolysis of the product. The N-carbobenzoxy derivative of this amino acid could be prepared easily and transformed to its p-nitrophenyl ester and t-butoxycarbonylhydrazide, but it was found difficult to obtain the methyl ester or the benzyl ester directly from this amino acid. Carbobenzoxy-Dl-β-(4-thiazolyl)-α-alanyl-glycine benzyl ester has been synthesized by several coupling methods: its yield decreased in the following order: p-nitrophenyl ester>dicyclohexylcarbodiimide (glycine ester was used as a free base)>dicyclohexylcarbodiimide (glycine ester p-toluenesul-fonate was used without triethylamine)>dicyclohexylcarbodiimide (glycine ester p-toluenesulfonate was used with triethylamine)>mixed anhydride. The alkaline hydrolysis of the protected di-peptide ester afforded the N-protected peptide in a good yield. Decarbobenzoxylation did not proceed smoothly by catalytic hydrogenation, in which hydrogen was absorbed slowly and incompletely, while it proceeded normally with hydrobromic acid in acetic acid.