4-Nitrophenyl activated esters are superior synthons for indirect radiofluorination of biomolecules

Mohammad B Haskali; Ashleigh L Farnsworth; Peter D Roselt; Craig A Hutton

doi:10.1039/d0md00140f

4-Nitrophenyl activated esters are superior synthons for indirect radiofluorination of biomolecules

RSC Med Chem. 2020 Jul 7;11(8):919-922. doi: 10.1039/d0md00140f. eCollection 2020 Aug 1.

Authors

Mohammad B Haskali^{1

2}, Ashleigh L Farnsworth^{3

4}, Peter D Roselt¹, Craig A Hutton^{3

4}

Affiliations

¹ The Centre for Molecular Imaging and Translational Research Laboratory , The Peter MacCallum Cancer Centre , Melbourne , Australia . Email: mo.haskali@petermac.org.
² Sir Peter MacCallum Department of Oncology , The University of Melbourne , Victoria 3010 , Australia.
³ School of Chemistry , The University of Melbourne , Victoria 3010 , Australia.
⁴ Bio21 Molecular Science and Biotechnology Institute , The University of Melbourne , VIC 3010 , Australia.

Abstract

Indirect radiolabelling has for a long time been the mainstay strategy for radiofluorination of biomolecules. Acylation of biomolecules through the use of an ¹⁸F-labelled activated ester is a standard method for indirect radiolabelling. However, the preparation of ¹⁸F-labelled activated esters is typically a complex and multistep procedure. Herein, we describe the use of 4-nitrophenyl (PNP) activated esters to rapidly prepare ¹⁸F-labelled acylation synthons in one step. Furthermore, we present a comparative study of PNP activated esters and the commonly utilised 2,3,5,6-tetrafluorphenyl (TFP) activated esters under direct radiofluorination conditions and demonstrate their relative acylation behaviour. We demonstrate the superiority of PNP esters under direct radiofluorination conditions with favourable acylation kinetics.