SYNTHESIS OF TETRAAZAMACROCYCLES; MRI CONTRAST/NMR SHIFT REAGENTS CONTAINING COMPLEXES OF SUCH MACROCYCLES WITH LANTHANIDES

摘要

The pH controlled selectivity of the sulfomethylation reaction is used to prepare a series of di-, tri-, tetra- and hexaazacyclomacrocycles with specified patterns of pendent side-chain chelating groups. The prepared mono and diacetic acid derivatives, together with monomethylenephosphonate and monomethylenephosphinate derivatives of [12]aneN4, [12]aneN3 and [9]aneN3, make these types of ligands easily available by a synthetic pathway that avoids the use of protective groups. The invention thus comprises a variety of compounds, methods and uses characterized by relatively high synthetic yields of polyazamacrocyclic ligands exhibiting a wide and predictable choice of metal ion binding constants water and lipid solubilities by reason of their substituent pendent groups.