Synthesis of macrocyclic peptide analogues of proteasome inhibitor TMC-95A.
The synthesis of three constrained macrocyclic peptide analogues 1 of TMC-95A as potential proteasome inhibitors is described. The key step involves a Ni(0)-mediated macrocyclization of tripeptides 2 bearing halogenated aromatic side chains for the formation of the biaryl junction. In addition, an enantioselective preparation of l-7-bromotryptophan methyl ester 3 using a Corey-O'Donnell alkylation of the glycine benzophenone imine was achieved in good overall yield with very high ee (>85%) on a multigram scale.
Berthelot
Alexandra
A
Institut de chimie de Rennes, Synthèse et électrosynthèse organiques, UMR 6510, Université de Rennes I, Campus de Beaulieu, F 35042 Rennes Cedex, France joelle.vidal@univ-rennes1.fr
Piguel
Sandrine
S
Le Dour
Gwennaël
G
Vidal
Joëlle
J
D000478:Alkylation; D001966:Bromine / Q000737:chemistry; D006841:Hydrocarbons, Aromatic / Q000737:chemistry; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D009842:Oligopeptides / Q000138:chemical synthesis; D010456:Peptides, Cyclic / Q000138:chemical synthesis*; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism; D014364:Tryptophan / Q000737:chemistry
D006841:Hydrocarbons, Aromatic; D006846:Hydrocarbons, Halogenated; D007097:Imines; D009842:Oligopeptides; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; C408291:TMC-95A; D014364:Tryptophan; D001966:Bromine