The synthetic access to 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione was significantly improved from an overall yield of 1% to 33%. The procedure involved the use of COCF3 or DDE as highly selective protecting groups for primary amines and of Boc to protect the secondary amine functions. The reaction of a tris-Boc protected tetraethylenepentamine with malonic acid gave the macrocycle in a 44% yield, the same reaction with malonyl chloride, however, yielded only 3.6% of the desired product. Boc deprotection and removal of the trifluoroacetate salts gave access to the final product, 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione, in an overall yield of 33%.
azamacrocycles - 1,4,7,10,13-pentaazacyclohexadecane-14,16-dione - protecting groups - cyclization - ligands
