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

Xiang-Guo Hu; Donald S Thomas; Renate Griffith; Luke Hunter

doi:10.1002/anie.201403071

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

Angew Chem Int Ed Engl. 2014 Jun 10;53(24):6176-9. doi: 10.1002/anie.201403071. Epub 2014 May 21.

Authors

Xiang-Guo Hu¹, Donald S Thomas, Renate Griffith, Luke Hunter

Affiliation

¹ School of Chemistry, UNSW Australia, Sydney NSW 2052 (Australia) http://www.chemistry.unsw.edu.au/research/research-groups/hunter-group.

PMID: 24848423
DOI: 10.1002/anie.201403071

Abstract

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.

Keywords: NMR spectroscopy; conformation analysis; cyclic peptides; gauche effect; stereoselective fluorination.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Halogenation / genetics*
Magnetic Resonance Spectroscopy
Models, Molecular
Molecular Structure
Peptides / chemistry*
Peptides, Cyclic / chemistry*
Stereoisomerism

Substances

Peptides
Peptides, Cyclic
unguisin A