RCM of tripeptide dienes containing a chiral vinylcyclopropane moiety: impact of different Ru-based catalysts on the stereochemical integrity of the macrocyclic products.
[structures: see text] Tripeptide dienes containing an (1R,2S)-vinyl aminocyclopropylcarboxylate residue were cyclized to beta-strand scaffolds under ring-closing metathesis (RCM). Conformational factors, ligand effects, and reaction conditions were evaluated. A protocol was developed for the efficient synthesis of 15-membered ring peptides in high diastereomeric purity. These peptides are key synthetic precursors to antiviral agents that target the hepatitis C virus and represent the first class of clinically validated pharmaceutical agents that are synthesized in large scale using RCM.
Poirier
Martin
M
Department of Chemistry, Boehringer Ingelheim (Canada) Ltd., Research and Development, 2100 Cunard Street, Laval, Quebec H7S 2G5, Canada.
Aubry
Norman
N
Boucher
Colette
C
Ferland
Jean-Marie
JM
LaPlante
Steve
S
Tsantrizos
Youla S
YS
D002384:Catalysis; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D009842:Oligopeptides / Q000737:chemistry*; D011407:Propane / Q000031:analogs & derivatives*; D013237:Stereoisomerism
D009842:Oligopeptides; D011407:Propane