Perfluorinated markers for hypoxia detection: synthesis of sulfur-containing precursors and [ 18F]-labelling

Abstract

Synthetic pathways of two novel sulfurated precursors for [ 18F]-labelling by oxidative fluorodesulfurization reaction are described. A three-step sequence starting from N-phthalimido-β-alanine allows the preparation of a new trithioorthoester as valuable precursor of the synthesis of [ 18F]-3,3,3-trifluoropropylamine, a convenient radiolabelled intermediate for [ 18F]-EF3. A five-step sequence for the preparation of methyl 4-phthalimido-2,2-difluoropropanedithioate from ethyl 2,2-difluoropropanoate, via the key conversion step of α,α′-difluorothioamidate to the corresponding α,α′-difluorodithioester, and the first results of its use as precursor for oxidative fluorodesulfurization in [ 18F]-radiochemistry are also presented.