Menthols as Chiral Auxiliaries for Asymmetric Cycloadditive Oligomerization: Syntheses and Studies of beta-Proline Hexamers

摘要

To produce a novel class of structurally ordered poly-beta-prolines, an emergent method for synthesizing chiral beta-peptide molecular frameworks was developed based on 1,3-dipolar cycloaddition chemistry of azomethine ylides. Functionalized short beta-peptides with up to six monomeric residues were efficiently synthesized in homochiral forms using a cycloadditive oligomerization approach. X-ray, NMR, and CD structural analyses of the novel beta-peptides revealed secondary structure features that were generated primarily by Z/E-beta-peptide bond isomerism. Anticancer in cellulo activity of the new beta-peptides toward hormone-refractory prostate cancer cells was observed and was dependent on the absolute configuration of the stereogenic centers and the chain length of the beta-proline oligomers.