Synthesis and reactions of new chiral linear and macrocyclic tetraand penta-peptide candidates

Abstract

A series of linear and macrocyclic pentapeptide derivatives have been prepared via the coupling of pyridine-2,6-dicarboxylic acid (1) or pyridine-2,6-dicarbonyl dichloride (2) with appropriate amino acid methyl esters. The coupling of 1 or 2 with aminoacid methyl esters gave the corresponding pyridine dipeptide methyl esters 3, which were hydrolyzed with sodium hydroxide to the corresponding acids 4. The latter compounds 4 were coupled with other amino acid methyl esters to afford the corresponding tetrapeptide esters 5, which were hydrolyzed with sodium hydroxide to the corresponding acids 6. Cyclization of tetrapeptide acids with L-lysine methyl ester or with aliphatic diamide derivatives afforded the corresponding cyclic pentapeptide methyl ester derivatives 7 and cyclic tetrapeptide diamines 8, respectively. Finally, hydrolysis with 1 N sodium hydroxide or hydrazinolysis with hydrazine hydrate of methyl esters 7 afforded the corresponding acids 9a - e and hydrazides 10a - e, respectively.