Total synthesis of the cyclopeptide alkaloid paliurine E. insights into macrocyclization by ene--enamide RCM.
The total synthesis of (-)-paliurine E is described in 14 steps and 11% overall yield. The first successful application of ene--enamide ring-closing metathesis for macrocyclization serves as the foundation for this synthesis and allowed for a straightforward installation of the challenging cyclic enamide together with the macrocycle. In the course of these synthetic studies, we also found that very subtle and minor structural modification of the enamide resulted in dramatic and unexpected changes of their reactivity since a primary amide or an aromatic aldehyde can be obtained after reaction with Grubbs' second-generation catalyst. Further insights on the macrocyclization by ene--enamide RCM are also discussed.
Toumi
Mathieu
M
Institut Lavoisier de Versailles, UMR CNRS 8180, Université de Versailles Saint Quentin en Yvelines, 45 avenue des Etats-Unis, 78035 Versailles Cedex, France.
Couty
François
F
Evano
Gwilherm
G
D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D000577:Amides / Q000737:chemistry*; D003500:Cyclization; D009682:Magnetic Resonance Spectroscopy; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared
D000470:Alkaloids; D000577:Amides; D010456:Peptides, Cyclic