From Desferrioxamine B Umpolung to an Enantiopure Bifunctional Chelator for Zr-immunoPET.

Promising results in preclinical diagnosis based on Zr-immunoPET have fostered the development of efficient chelators for this tetravalent metal. Leads in this area are octadentate ligands obtained by extension of the desferrioxamine B trihydroxamic acid DFO with a fourth bidentate ligand. In the approach reported here, the latter is a natural 6-membered cyclic hydroxamic acid deriving from (L)-ornithine. Its coupling to DFO via an (L)-lysine spacer required that the genuine amine function of the DFO terminus be changed to a carboxylic acid. Such a requirement prompted us to explore short sequences of chemical transformations that would challenge total syntheses leading to the same products. As a matter of fact, the target C-terminal DFO analogue was obtained in benzyl-protected form in three steps from commercially available DFO in 16% overall yield. Our short-step approach allowed us to implement other functionalities without DFO extension: -OH, -OTs, -CHO, -C(O)CH, and -CH═CH.