Light-induced Hetero-Diels Alder cycloaddition as a new coupling method to biomolecule radiolabeling

The formation of a C-18F bond requires hard conditions which is problematic for the biomolecule radiolabelling. The alternative method which has been developed since a few decades consists in incorporating the 18F on a prosthetic group and coupling it to the biomolecule. The copper (I)-catalysed 1,2,3-triazole formation involving azides and terminal alkynes is a powerful and rapid method of coupling but present the inconvenient of the employment of cytotoxic reagents. The photoclick conjugation is a promising alternative with no need of catalyst[1]. Recently, a light-induced hetero-Diels Alder cycloaddition involving a 3-(hydroxymethyl)-2-naphthol derivative and an electron-rich olefin has been developed[2]. This reaction seems well adapted for the fast conjugation of radionuclides to biomolecules. Herein we report the synthesis of a [18F]fluoronaphtoquinone derivative as prosthetic group and its reaction with vinyl ethers.