Facile Synthesis and Antimicrobial Evaluation of New Chiral Macrocyclic Hydrazone and Tricyclopolyazacarboxamide Candidates Incorporating Amino Acid and Pyridine Moieties

A series of macrocyclic Schiff-bases and hexadecaazatricyclo-carboxamides has been prepared via the cyclocondensation of pyridine-2,6-dicarbonyl dichloride (1) or pyridine-2,6-dicarboxylic acid dihydrazide (3) or N, N-bis-[1-hydrazinyl-2-(substituted)]-pyridine-2,6-dicarboxamides (5a-d) with appropriate difunctional reagents. The coupling of 3 with tertacarboxylic acid dianhydride gave the macrocyclic tetraimidetetracarboxamides 6 and 7. Condensation of 5a-d with 3,3'-binaphthyl-dialdehyde yielded the corresponding macrocyclic hydrazones 8a-d, while compound 5a reacted with tertacarboxylic acid dianhydrides to give macrocyclic tetraimide octacarboxamide pyridine derivatives 9 and 10. The tricyclo-8,18-dimethyl ester derivative 12 was chemically synthesized, starting from the acid chloride 1 by coupling with L-lysine methyl ester. The tricyclo-8,18-dimethyl ester derivative 12 was treated with hydrazine hydrate to afford the corresponding hydrazide 13, which was condensed with aromatic aldehydes to afford tricyclo-bis-hydrazones 14a,b. The structure assignments of the new compounds are based on chemical and spectroscopic evidence. The biological activity screening tests showed that many of the obtained compounds exhibit high antimicrobial activity comparable to ampicillin and chloramphenicol which are used as reference compounds.