Synthetic route for 18F labeled triazole-modified oligonucleotides through a new late-stage desulfurative fluorination methodology

This dissertation is thought as a complete collection of all the concepts useful to produce sulfides that can be used in desulfurative halogenation reactions. Particular emphasis is placed on desulfurative fluorination and its possible application for 18F labeling, and the methodology recently developed is described in detail focusing on the challenges encountered in the optimization of the method. A synthetic route for labeled macromolecules is conceptualized, preparing a sulfidoazide probe that can be coupled through “click” triazole linkage. Exploiting highly selective late-stage fluorination the probe could be used for 18F labeling of oligonucleotides acting as a “light bulb" for medical studies through PET imaging. A sustainability assessment of the synthetic route has been performed, following the principles of Green Chemistry, revealing the critical steps and materials. Great attention is placed on the synthesis of thiophenyl (-SPh) sulfide precursors, to have a comprehensive view and explore the possible applications of the method in the field of (bio-)organic chemistry.