Stereoselective terminal functionalization of small peptides for catalytic asymmetric synthesis of unnatural peptides.
The asymmetric phase-transfer catalytic alkylation of peptides has been achieved by the use of designed C(2)-symmetric chiral quaternary ammonium bromide 1 as catalyst. Excellent stereoselectivities were uniformly observed in the alkylation with a variety of alkyl halides and the efficiency of the transmission of stereochemical information was not affected by the side-chain structure of the preexisting amino acid residues. This method also enables an asymmetric construction of noncoded alpha,alpha-dialkyl-alpha-amino acid residues at the peptide terminal. Since this chirality can be efficiently transferred to the adjacent amino acid moiety, our approach provides a general procedure not only for the highly stereoselective terminal functionalization of peptides but also for the sequential asymmetric construction of unnatural oligopeptides, which should play a vital role in the peptide-based drug discovery process.
Maruoka
Keiji
K
Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan. maruoka@kuchem.kyoto-u.ac.jp
Tayama
Eiji
E
Ooi
Takashi
T
D000478:Alkylation; D002384:Catalysis; D019906:Nuclear Magnetic Resonance, Biomolecular; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry*; D012545:Schiff Bases; D017550:Spectroscopy, Fourier Transform Infrared; D013237:Stereoisomerism
D010455:Peptides; D012545:Schiff Bases