Synthesis and hydrolytic stability of novel 3-[18F]fluoroethoxybis(1-methylethyl)silyl]propanamine-based prosthetic groups

Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepared in good yields. These silicon groups bearing an acid or an azide group were coupled to a model tripeptide (Leu-Gly-Gly) either through a classical amide bond formation or through “click chemistry” via the Huisgen cycloaddition. The radiolabelling with fluorine-18 by substitution of the ethoxy group at silicon has been carried out with success in 51–54% decay corrected radiochemical yields. Radiolabelled peptides were easily prepared by direct 18F-fluorination of the silicon-bearing tripeptide or by coupling the peptide with a radiolabelled silicon-based prosthetic group. Their stabilities in physiological medium were studied and proved poor.

Graphical abstractSilicon based prosthetic groups were synthesized and coupled to a tripeptide through an amide bond formation or a Huisgen cycloaddition. 18F-Labelling of these precursors gave the radiolabelled peptide.Figure optionsDownload full-size imageDownload as PowerPoint slideResearch highlights► New fluorine-18 radiolabelled silicon-based molecules are designed as prosthetic groups. ► Successful coupling of these groups to a tripeptide was carried out by two different methods. ► The 18F-labelling of the tripeptide was achieved by direct and indirect methods.