Stereoselective fluorination alters the geometry of a cyclic peptide: exploration of backbone-fluorinated analogues of unguisin A.

New methods for enhancing the efficiency of peptide cyclization, and for fine-tuning the conformations of cyclic peptides, are valuable from a drug development perspective. Herein stereoselective fluorination is investigated as a new strategy for achieving these goals. Four vicinal difluorinated analogues of the natural cyclic heptapeptide unguisin A have been efficiently synthesized. The analogues are found to adopt dramatically different secondary structures, controlled by the fluorine stereochemistry.