Synthesis of chiral linear and macrocyclic candidates: VI. Synthesis and antibacterial activity of some macrocyclic tripeptides and linear dipeptide Schiff bases

Abstract

A series of macrocyclic tripeptides and linear dipeptide Schiff base derivatives has been synthesized using pyridine-3,5-dicarboxylic acid and L-phenyalanine methyl ester as starting materials. Treatment of pyridine-3,5-dicarbonyl dichloride with L-phenylalanine methyl ester gave N,N′-(pyridine-3,5-diyldicarbonyl)bis(L-phenyalanine methyl ester) which was hydrolyzed with 1N sodium hydroxide to the corresponding bis-acid, and the latter was cyclized with diamino acids to afford macrocyclic tripeptide derivatives. The reaction of the bis ester with hydrazine hydrate gave bis-hydrazide, which was condensed with aldehydes to obtain the corresponding Schiff base derivatives. The structures of the newly synthesized compounds were confirmed by IR, 1H and 13C NMR, and MS spectral data and elemental analyses. The antimicrobial activities of some of the newly synthesized compounds were comparable with that of Streptomycin used as control.