4b

A series of chiral linear carboxamide derivatives (2- 15) with an incorporated peptide linkage have been prepared via the coupling of 1-ethyl-1,4-dihydro-7-methyl-4-oxo-quinoline-3-carboxylic acid (nalidixic acid, 1) with appropriate amino acid methyl esters. Coupling of 1 with amino acid methyl esters gave the corresponding peptide methyl esters 2, which were hydrolyzed with methanolic sodium hydroxide to the corresponding acids 3. Hydrazinolysis of esters 2with hydrazine hydrate afforded the corresponding acid hydrazide derivatives 4. The latter compounds were coupled with appropriate aldehydes or acetophenone derivatives to afford the corresponding Schiff base derivatives 5 and 6, respectively. The hydrazide derivative was reacted with phenyl isothiocyanate or carbonyl derivatives to give the corresponding thiosemicarbazide 7 and compounds 8- 10, respectively. Also, 4b was treated with acid monoanhydrides to give the corresponding imide derivatives 11- 13. Finally, 4b was reacted with tetracarboxylic acid dianhydride derivatives to afford the corresponding diimido carboxamide derivatives 14 and 15

Graphical Abstract

Synthesis and Reactions of New Chiral Linear Carboxamides with an Incorporated Peptide Linkage Using Nalidixic Acid and Amino Acids as Starting Materials