Radiosynthesis of 5-[18F]Fluoro-1,2,3-triazoles through Aqueous Iodine-[18F]Fluorine Exchange Reaction.

Xiang Zhang,Falguni Basuli,Rolf Swenson,Sameh Abdelwahed,Tadhg Begley

doi:10.3390/molecules26185522

Abstract

In this report, a simple and efficient process to achieve fluorine-18-labeled 1,2,3-triazole is reported. The heteroaromatic radiofluorination was successfully achieved through an iodine–fluorine-18 exchange in an aqueous medium requiring only trace amounts of base and no azeotropic drying of fluorine-18. This methodology was optimized on a model reaction and further validated on multiple 1,2,3-triazole substrates with 18–60% radiochemical conversions. Using this strategy—the radiosynthesis of a triazole-based thiamin analogue—a potential positron emission tomography (PET) probe for imaging thiamin-dependent enzymes was synthesized with 10–16% isolated radiochemical yield (RCY) in 40 min (uncorrected, n > 5).

Highlights

Fluorine-18 exchange in an aqueous medium requiring only trace amounts of base and no azeotropic drying of fluorine-18
The simplicity and highly efficient nature of CuAAC have enabled numerous applications of this process in the radiosyntheses of both small molecules [23,24,25] and macromolecules [26,27,28,29]. This method requires multi-step radiosynthesis: the azeotropic drying of fluorine-18, the incorporation of fluorine-18 on the alkyl- or azide- substrates, and the purification of the labeled substrate followed by click reaction with biomolecules
After the success of the aqueous [18F]IFX radiofluorination with a wide range of substrates, we focused on the development of a novel positron emission tomography (PET) tracer, [18F]15 (Figure 3), a potential

Summary

Introduction

Fluorine-18 exchange in an aqueous medium requiring only trace amounts of base and no azeotropic drying of fluorine-18 This methodology was optimized on a model reaction and further validated on multiple 1,2,3-triazole substrates with 18–60% radiochemical conversions. The simplicity and highly efficient nature of CuAAC have enabled numerous applications of this process in the radiosyntheses of both small molecules [23,24,25] and macromolecules [26,27,28,29] This method requires multi-step radiosynthesis: the azeotropic drying of fluorine-18, the incorporation of fluorine-18 on the alkyl- or azide- substrates, and the purification of the labeled substrate followed by click reaction with biomolecules. Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations

Methods

Discussion

Conclusion