18F]fluoro-3-hydroxymethylbutyl)guanine ([ 18F]FHBG) and 9-[(3-[ 18F]fluoro-1-hydroxy-2-propoxy)methyl]guanine ([ 18F]FHPG)]]>

摘要

Graphical abstractDisplay OmittedHighlights?NewO6-carbamoyal protected precursors for [18F]FHBG synthesized.?NovelO6-tert-butyl-N2-monomethoxytrityl precursors for [18F]FHBG and [18F]FHPG synthesized.?These precursors were fully characterized by NMR and MS.?These precursors gave excellent radiochemical yields for [18F]FHBG and [18F]FHPG.AbstractA new, high radiochemical yield synthesis of [18F]FHBG and [18F]FHPG, the most popular imaging agents currently in use for monitoring gene therapy using positron emission tomography (PET), is reported in this work. Protection of sensitive sites in the precursors generally utilized for the preparation of [18F]FHBG and [18F]FHPG using the nucleophilic18F-fluorination reaction was found to be critical for good radiochemical yields, reliability and reproducibility of the synthetic process. As an initial approach, protection atO6-oxygen in the guanine moiety of the currently used monomethoxytrityl-protected penciclovir tosylate derivative9with carbamoyl groups was carried out. Subsequently, full protection of bothO6-oxygen andN2-nitrogen in the monomethoxytrityl-protected penciclovir and ganciclovir tosylate analogs9and10were achieved by their reaction with di-tert-butyl dicarbonate, which resulted inO6-tert-butyl-N2-Boc-monomethoxytrityl-protected penciclovir tosylate18andO6-tert-butyl-N2-Boc-monomethoxytrityl-protected ganciclovir tosylate19, respectively. The newly synthesized carbamoyl- and the Boc- protected precursors were first reacted with non-radioactive KF complexed with Kryptofix 222 to isolate the fluorinated products. Acid hydrolysis of the purified fluor