Late-stage (radio)fluorination of alkyl phosphonates via electrophilic activation.

Autor: Zhang K; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China., Feng W; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China., Mou Z; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China., Zhang L; Tianjin Engineering Technology Center of Chemical Wastewater Source Reduction and Recycling, School of Science, Tianjin Chengjian University, Tianjin, China., Ma M; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China.; Department of Nuclear Medicine, Xiang'an Hospital affiliated to Xiamen University, Xiamen, Fujian, China., Zhao Z; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China., Liu X; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China., Chen X; Departments of Diagnostic Radiology, Surgery, Chemical and Biomolecular Engineering, and Biomedical Engineering, Yong Loo Lin School of Medicine and College of Design and Engineering, National University of Singapore, Singapore, Singapore.; Clinical Imaging Research Centre, Centre for Translational Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Nanomedicine Translational Research Program, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.; Institute of Molecular and Cell Biology, Agency for Science, Technology, and Research (A*STAR), 61 Biopolis Drive, Proteos, Singapore, Singapore., Li Z; State Key Laboratory of Vaccines for Infectious Diseases, Center for Molecular Imaging and Translational Medicine, School of Public Health, Xiamen University, Xiamen, Fujian, China. zijing.li@xmu.edu.cn.; Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen, Fujian, China. zijing.li@xmu.edu.cn.; State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics, National Innovation Platform for Industry-Education Integration in Vaccine Research, Xiamen University, Xiamen, Fujian, China. zijing.li@xmu.edu.cn.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2024 Nov 28; Vol. 15 (1), pp. 10338. Date of Electronic Publication: 2024 Nov 28.
DOI: 10.1038/s41467-024-54208-y
Abstrakt: Constructing organic fluorophosphines, vital drug skeletons, through the direct fluorination of readily available alkyl phosphonates has been impeded due to the intrinsic low electrophilicity of P V and the high bond energy of P═O bond. Here, alkyl phosphonates are electrophilically activated with triflic anhydride and N-heteroaromatic bases, enabling nucleophilic fluorination at room temperature to form fluorophosphines via reactive phosphine intermediates. This approach facilitates the late-stage (radio)fluorination of broad dialkyl and monoalkyl phosphonates. Monoalkyl phosphonates derived from targeted drugs, including cyclophosphamide, vortioxetine, and dihydrocholesterol, are effectively fluorinated, achieving notable yields of 47-71%. Radiofluorination of medically significant 18 F-tracers and synthons are completed in radiochemical conversions (radio-TLC) of 51-88% and molar activities up to 251 ± 12 GBq/μmol (initial activity 11.2 GBq) within 10 min at room temperature. Utilizing a phosphonamidic fluoride building block (BFPA), [ 18 F]BFPA-Flurpiridaz and [ 18 F]BFPA-E[c(RGDyK)] 2 demonstrate high-contrast target imaging, excellent pharmacokinetics, and negligible defluorination.
Competing Interests: Competing interests: The authors declare no competing interests.
(© 2024. The Author(s).)
Databáze: MEDLINE
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