Synthesis and Biological Evaluation of Some Dipeptide Derivatives and Their Heterocyclic Compounds

Abstract

The protected dipeptide esters (3a-e, 4a-l) is prepared by the reaction of compounds (1a-e, 2a-d) with dicyclohexylcarbodiamide (as coupling reagent) and amino acid esters .Thereafter hydrazides (5a-e, 6a-j) are obtained by the reaction of corresponding esters with hydrazine hydrate. Hydrazones (7a-e, 8a-e) are synthesized by the reaction of the above hydrazides with p-nitro benzaldehyde , which was cyclized to 2,5- disubstituted 1,3,4- oxadiazole (9a-e, 10a-e) through lead oxide and to phthalazines (13a-b) through hydrochloric acid. 1,3,4- oxadiazole -2- thione (11a-b, 12a-e) were prepared by the reaction of the corresponding hydrazides with carbon disulfide in alcoholic potassium hydroxide. Hydrazides were reacted with ammonium thiocyanate to afford thiosemicarbazide (14a-c) which were cyclized to 1,2,4- triazole -3- thione  (15a-b) in sodium hydroxide medium. The structures of the synthesized compounds were confirmed by physical and spectral methods. The antibacterial activity of the prepared compounds (5d_, 7a, 9e, 10d, 11a, 12e, 13a, 14b) against the gram +ve and –gram –ve Bactria (Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Proteus mirabilis) were studied and discussed