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

Author(s): Xabier Guarrochena, Julia Kronberger, Manuel Tieber, Philipp Ciesielski, Thomas L. Mindt, Irene V.J. Feiner
Abstract: 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.
Organisation(s): Department of Inorganic Chemistry, Joint Applied Medicinal Radiochemistry Facility
External organisation(s): ABX - Advanced Biochemical Compounds, Ludwig Boltzmann Intitute Applied Diagnostics, Vienna Doctoral School in Chemistry (DoSChem), Medizinische Universität Wien
Journal: ChemMedChem
Volume: 19
ISSN: 1860-7179
DOI: https://doi.org/10.1002/cmdc.202300495
Publication date: 02-2024
Peer reviewed: Yes
Austrian Fields of Science 2012: 301305 Medical chemistry, 301206 Pharmacology
Keywords
ASJC Scopus subject areas: Biochemistry, Molecular Medicine, Pharmacology, Drug Discovery, Pharmacology, Toxicology and Pharmaceutics(all), Organic Chemistry
Portal url: https://ucrisportal.univie.ac.at/en/publications/c4dac4ae-be9f-414a-9a6b-0c8818959996