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

Synthetic pathways of two novel sulfurated precursors for 18F]-labelling by oxidative fluorodesulfurization reaction are described. A three-step sequence starting from N-phthalimido-beta-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 alpha,alpha'-difluorothioamidate to the corresponding alpha,alpha'-difluorodithioester, and the first results of its use as precursor for oxidative fluorodesulfurization in 18F]-radiochemistry are also presented.