898831-79-3Relevant academic research and scientific papers
Stereoselective synthesis of (Z)-alkene-containing proline dipeptide mimetics
Sasaki, Yoshikazu,Niida, Ayumu,Tsuji, Takashi,Shigenaga, Akira,Fujii, Nobutaka,Otaka, Akira
, p. 4969 - 4979 (2007/10/03)
In peptides and proteins, the peptide bond between an amino acid and proline exists as an equilibrium mixture of the cis-imide and trans-imide due to the low energy barrier in their interconversion. This feature greatly influences the structure and function of the proline-containing peptides and proteins. Therefore, restricting the amide bond with an (E)- or (Z)-alkene should provide a promising method for elucidating the structure-activity relationships of the peptide and the proteins. In this report, the regio-and stereoselective synthesis of cis-alanylproline (Ala-Pro) type (Z)-alkene dipeptide mimetic is described. The key steps of this synthesis are to introduce a C3 unit onto a γ-phosphoryloxy-α,β-unsaturated-(3-lactam with an organocopper-mediated anti-SN2′ reaction and subsequently construct a five-membered proline-like cyclic structure with an intramolecular Suzuki coupling reaction. Hydrolysis of the amide bond in the resulting bicyclic lactam yields the desired cis-Ala-Pro type (Z)-alkene dipeptide isostere. The presented synthetic methodology should be applicable to the general syntheses of other cis-aminoacylproline type (Z)-alkene dipeptide mimetics.
