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.
School of Chemistry, UNSW Australia, Sydney NSW 2052 (Australia) http://www.chemistry.unsw.edu.au/research/research-groups/hunter-group.
Xiang-Guo
XG
Hu
Donald S
DS
Thomas
Renate
R
Griffith
Luke
L
Hunter
D054879:Halogenation / Q000235:genetics*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000737:chemistry*; D013237:Stereoisomerism
D010455:Peptides; D010456:Peptides, Cyclic; C561693:unguisin A
NMR spectroscopy; conformation analysis; cyclic peptides; gauche effect; stereoselective fluorination