開催日: 2017/09/20 - 2017/09/22
Biologically active oligo peptides consisting of less than 20 amino acids are particularly valuable for the development of drugs. In fact, they account for three-fourths of the existing marketed peptide drugs. Feglymycin is a biologically active oligopeptide containing 13 amino acids including highly racemizable 3,5-dihydroxyphenylglycines (Dpgs). Biological activity of feglymycin involving strong anti-HIV activity and moderate antimicrobial activity and its unique helical conformation make feglymycin an attractive lead compound for drug development. We achieved a total synthesis of feglymycin based on a linear/convergent hybrid synthetic approach. Our originally developed micro-flow amide bond formation enabled the efficient preparation of hexapeptide and heptapeptide intermediates containing highly racemizable Dpgs based on a linear synthetic approach that was previously considered impossible. The developed synthetic approach will be useful for the rapid preparation of feglymycin analogues in the future. Our micro-flow amide bond formation uses triphosgene, and only emits CO2 and the HCl salt of DIEA. One of the advantages of using micro reactors is the ease of scaling up. Our developed process can be scaled by either continuous running or by the numbering up of the microreactors. This process will enable a practical preparation of biologically active oligopeptides containing highly racemizable amino acids.