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

Syntbetic pathways of two novel sulfurated precursors for [F-18]-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 [F-18]-3,3,3-trifluoropropylamine, a convenient radiolabelled intermediate for [F-18]-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 [F-18]-radiochemistry are also presented. (C) 2004 Elsevier Ltd. All rights reserved.