Design and synthesis of phosphorylated pyridine-based ligands for lanthanide complexation. Part 1

A family of naphthalene-pyridine based ligands were synthesized stepwise from glyphosate and amino-di(methylenediethylphosphite). The linker is a flexible chain bearing a terminal ester or a Biotin fragment. Several new ligands constructed from a pyridine-ethynylnaphthalene platform have been engineered with a chelating pocket comprising bisdimethylaminocarboxylate/phosphonate or bisdimethylaminophosphonate units. Selective hydrolysis provides pockets with four to six anionic carboxylate or phosphate functions suitable for lanthanide complexation. Linkage at the opposite side of a flexible hanging arm either via a triple bond or through an amide tether offers the possibility of further use of these ligands for bioconjugation. Protocols to link the dedicated pockets via hydrophilic flexible chain to Biotin are also detailed.