Conférence 21 novembre 2024

Pr Denis Giguère (Université Laval, Québec, Canada)

Carbohydrate Approach to Multivicinal Fluorinated and Inter-Halide Stereocenters

In recent years the synthesis of multivicinal organofluorines has gained attention and their properties have been widely studied. Recently our group reported the synthesis of several polyfluorinated analogues of carbohydrates using a Chiron approach and investigated the effect of this element on physicochemical properties such as solution- and solid-state conformation and lipophilicity.

To our surprise, multivicinal inter-halides have been ignored from the chemical landscape and efficient synthetic routes leading to these compounds as well as their properties remain unknown.

The synthesis of multivicinal inter-halides stereotriads and -tetrads started from levoglucosan and allowed us to obtain novel compounds with an excellent stereocontrol and good yields. The solution-state were established using a J-based configurational analysis and the lipophilicity was assessed with a log Pdetermination method based on ¹⁹F NMR spectroscopy. Synthetic application of these compounds in drug discovery was explored with the synthesis of halogenated pitolisant analogues and other medically relevant molecules.