An efficient synthesis of ([ 18F]fluoropropyl)quinoline-5,8-diones by rapid radiofluorination–oxidative demethylation

Abstract

Since many molecules bearing quinoline-5,8-dione or fused 1,4-quinone moieties possess a wide spectrum of biological activities, efficient methods for incorporation of fluorine-18 (F-18) into quinoline-5,8-diones have received considerable attention in positron emission tomography (PET) molecular imaging studies. In this paper, we describe an efficient synthetic route for the regioselective preparation of fluoropropyl-substituted quinoline-5,8-diones on the C3, C4, and C6 positions by tert-alcohol media fluorination, followed by oxidative demethylation of the corresponding dimethoxy compound using N-bromosuccinimide (NBS) in the presence of catalytic amounts of sulfuric acid. Moreover, F-18 labeled [ 18F]fluoropropylquinoline-5,8-diones [ 18F] 21– 23 were prepared from the corresponding mesylate precursors by a method of rapid and efficient one-pot, two-step reactions: radiofluorination using TBA [ 18F]F generated under no-carrier-added (NCA) conditions; oxidative demethylation, resulting in a 45% radiochemical yield of [ 18F] 21– 23 (decay-corrected) with a total synthesis time (including HPLC purification) of 75 min and high radiochemical purity (>99%), as well as high specific activity (∼230 GBq/μmol).