Synthesis of vicinal bisamidines and bisaminals for the preparation of tetraazamacrocycles and the synthesis of cross-bridged cyclam derivatives and studies on their complexation of small cations

Abstract

A new methodology for the preparation of tetraazamacrocycles is presented. This new methodology utilizes a regioselective reduction of vicinal bisaminals (33) and bisamidines (16) precursors to afford ring expanded tetraamines. This chemistry has provided a synthetic route for the preparation of benzocyclam (34), a compound whose preparation is unreported in the literature.*. This methodology has aided in the preparation of cross-bridged cyclam derivatives (83, 92, 95). Cross-bridged cyclam derivatives are bicyclic tetraamines which adopt low energy conformations appropriate for the complexation of small cations. Cross-bridged cyclam derivatives have potential utility in clinical and nuclear medicine as well as bioinorganic chemistry. The preparation of new derivatives of cross-bridged cyclam and studies on their chemistry are presented.*. Cross-bridged cyclam derivatives are good complexers of Li+. In fact, cross-bridged cyclam derivatives complex Li+ selectively over Na+. Ligands which can selectively bind Li+ in the presence of Na+ would have significant utility as Li + sensors which could monitor small concentrations of Li+ in the presence of abundant Na+. Experiments on the relative selectivity for cross-bridged cyclam ligands for Li+ and Na + as well as the relative complexation ability between ligands is presented