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

• Published in: RSC medicinal chemistry Vol. 11; no. 8; pp. 919 - 922
• Main Authors: Haskali, Mohammad B, Farnsworth, Ashleigh L, Roselt, Peter D, Hutton, Craig A
• Format: Journal Article
• Language: English
• Published: England 01-08-2020
• ISSN: 2632-8682; 2632-8682
• DOI: 10.1039/d0md00140f

Indirect radiolabelling has for a long time been the mainstay strategy for radiofluorination of biomolecules. Acylation of biomolecules through the use of an
18
F-labelled activated ester is a standard method for indirect radiolabelling. However, the preparation of
18
F-labelled activated esters is typically a complex and multistep procedure. Herein, we describe the use of 4-nitrophenyl (PNP) activated esters to rapidly prepare
18
F-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.
A comparative study of PNP- and TFP-activated esters of radiolabelled prosthetic groups demonstrates the superiority of PNP esters in terms of stability and yields for use in one-step radiolabelling of small molecules and peptides.