Straightforward Synthesis of DFO* - An Octadentate Chelator for Zirconium-89

DFO* is an octadentate chelator able to form highly stable chelates with Zirconium-89 (⁸⁹Zr) for nuclear medicinal applications in Positron Emission Tomography (PET).^[1,2] The synthesis of DFO* and its scale-up remains challenging by reported synthetic protocols. For this reason, we set out to develop a de novo synthesis of a hydroxamate-containing building block suitable for the coupling to the commercially available DFO (desferrioxamine B, mesylate salt) yielding, after deprotection, the desired chelator DFO* in a more efficient procedure. Highlights of the new synthesis of DFO* reported herein are less synthetic steps and the isolation of the desired product DFO* by using solid phase extraction (SPE), thus avoiding tedious HPLC purification. DFO* is obtained in excellent purity (92-98 %) and an overall yield of approximately 29 %. In addition, the isolated trifluoroacetic acid (TFA)-salt of DFO* displays an improved solubility in organic solvents (DMSO, DMF, methanol), which will facilitate its use for the preparation of structurally diverse derivatives suitable for bioconjugation chemistry and the development of ⁸⁹Zr-labeled radiotracers.