Multiple on-resin olefin metathesis to form ring-expanded analogues of the lantibiotic peptide, lacticin 3147 A2.
Chemical synthesis of lantibiotic analogues wherein monosulfide bridges are replaced with other groups can shed light on structure-activity relationships and generate variants that are resistant to aerobic oxidation and have better metabolic stability. This work describes the first complete synthesis of a carbocyclic lantibiotic analogue 2, using sequential on-resin ring-closing olefin metathesis and solution-phase peptide synthesis. The methodology described should find wide application for the preparation of rigidified peptidomimetics containing multiple carbocyclic rings. [structure: see text].
Pattabiraman
Vijaya R
VR
Department of Chemistry, University of Alberta, Edmonton, Alberta, Canada T6G 2G2.
Stymiest
Jake L
JL
Derksen
Darren J
DJ
Martin
Nathaniel I
NI
Vederas
John C
JC
D000475:Alkenes / Q000737:chemistry*; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis*; D001430:Bacteriocins / Q000138:chemical synthesis*; D003500:Cyclization; D008958:Models, Molecular; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D000475:Alkenes; D000900:Anti-Bacterial Agents; D001430:Bacteriocins; C082508:lacticin 481