The synthesis of L-proline derived hexaazamacrocyclic ligands of C-3 symmetry via intramolecular methyl ester aminolysis

A convenient synthesis of enantiomerically pure 18-, 21-. and 24-membered h exaaza-crown ligands is presented. Linear alpha,omega -aminoesters, prepare d from L-proline, undergo intramolecular aminolysis to afford the correspon ding 18-, 21-, and 24-membered macrocyclic amides in satisfactory yields (4 2, 65. and 22%, respectively). These were subsequently transformed into the title macrocyclic hexamines via exhaustive reduction with a borane-dimethy lsulfide complex. X-Ray structures of two larger macrocyclic amides are als o presented. (C) 2001 Elsevier Science Ltd. All rights reserved.