Method for synthesizing iodo- or astatoarenes using diaryliodonium salts
Inventors
GUERARD, François • Gestin, Jean-François • Brechbiel, Martin W. • Lee, Yong-Sok
Assignees
Centre National de la Recherche Scientifique CNRS • Universite dAngers • Universite de Nantes • Institut National de la Sante et de la Recherche Medicale INSERM • US Department of Health and Human Services
Publication Number
US-10858306-B2
Publication Date
2020-12-08
Expiration Date
2036-11-24
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Abstract
The present invention concerns a method of synthesizing a iodo- or astatoarene comprising the reaction of a diaryliodonium compound with a iodide or astatide salt, respectively. The invention also relates to said iodo- or astatoarene and diaryliodonium compound as such. The invention also concerns a method of synthesizing a iodo- or astatolabelled biomolecule and/or vector using said iodo- or astatoarene.
Core Innovation
The invention concerns a method of synthesizing iodo- or astatoarenes by reacting diaryliodonium compounds with iodide or astatide salts, respectively. It also relates to the iodo- or astatoarene compounds produced, the diaryliodonium compounds, and methods for synthesizing iodo- or astatolabeled biomolecules and/or vectors using these iodo- or astatoarenes.
The problem addressed arises from limitations in existing methods to produce radioiodinated and astatinated aromatic compounds used in nuclear medicine. Conventional reactions such as nucleophilic substitution by halogen exchange, electrophilic substitution, or halodemetallation often suffer from low radiochemical yields, low specific activity, and toxicity issues from precursors and side products. Particularly for astatination, controlling the oxidation state of astatine is challenging, leading to mixtures of species and instability due to radiation effects.
The innovation provides a method which surprisingly achieves high and consistent yields of iodo- or astatoarenes by reacting diaryliodonium compounds with iodide(-I) or astatide(-I) salts. The method is less toxic than iodo- or astatodestannylation methods, avoids intermediate tin compounds, and uses astatine in the (-I) oxidation state. Additionally, a simpler and faster purification technique is disclosed using solvent extraction (e.g., diethylether) instead of chromatography such as HPLC, reducing product loss and enabling industrial-scale application. Notably, the method reveals unexpectedly higher reactivity of astatide compared to iodide in this reaction context.
Claims Coverage
The patent discloses two independent claims covering novel astatoarene compounds and diaryliodonium salts, each defined by specific chemical formulae and substituents.
astroarene compounds defined by novel formulae
The invention claims astatoarene compounds having specific chemical structures as illustrated in the formulae provided, encompassing a range of substituents and halogen atoms including astatine.
diaryliodonium salts with tailored aryl and heteroaryl substituents
The invention claims diaryliodonium salts characterized by particular (C6-C10)aryl and heteroaryl groups substituted by diverse functional groups such as alkyl, alkynyl, halogens, maleimidyl, and others, enabling efficient synthesis of iodo- and astatoarenes.
The independent claims define novel chemical entities—astatoarene compounds and diaryliodonium salts—with specific structural features designed to facilitate efficient, high-yield synthesis of radioiodinated and astatinated aromatic compounds with improved properties.
Stated Advantages
Provides high and consistent yields of iodo- or astatoarenes, particularly with astatide.
Enables a simpler, faster, and low-cost purification process via solvent extraction instead of HPLC chromatography.
Reduces toxicity by avoiding intermediate tin-containing compounds used in conventional halodemetallation methods.
Uses astatine in the (-I) oxidation state, improving stability and control over the astatination process.
Documented Applications
Synthesis of radioiodo- or radioastatoarene compounds useful in nuclear medicine.
Preparation of radiolabeled biomolecules and vectors by conjugation of the iodo- or astatoarene compounds to biomolecules or vectors.
Use of radiolabeled biomolecules and vectors in the treatment and/or localization of tumors via imaging or therapy.
Radiolabeling methods for biomolecules and vectors employing bioorthogonal functional groups for selective conjugation.
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