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

Kaiqiang Zhang, Wanru Feng, Zhaobiao Mou, Lei Zhang, Mengting Ma, Zixiao Zhao, Xia Liu, Xiaoyuan Chen and Zijing Li ()
Additional contact information
Kaiqiang Zhang: Xiamen University
Wanru Feng: Xiamen University
Zhaobiao Mou: Xiamen University
Lei Zhang: Tianjin Chengjian University
Mengting Ma: Xiamen University
Zixiao Zhao: Xiamen University
Xia Liu: Xiamen University
Xiaoyuan Chen: National University of Singapore
Zijing Li: Xiamen University

Nature Communications, 2024, vol. 15, issue 1, 1-12

Abstract: Abstract 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 PV 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 18F-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), [18F]BFPA-Flurpiridaz and [18F]BFPA-E[c(RGDyK)]2 demonstrate high-contrast target imaging, excellent pharmacokinetics, and negligible defluorination.

Date: 2024
References: View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-54208-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-54208-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-54208-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().