Total Synthesis of the Highly N-Methylated Acetylene-Containing Anticancer Peptide Jahanyne

摘要

The first total synthesis of the highly N- methylated acetylene-containing lipopeptide jahanyne, an apoptosis-inducing natural product from marine cyanobacteria, is reported. A late-stage solution-phase coupling enabled introduction of the C -terminal ketone pyrrolidine moiety. A modified Fmoc solid-phase synthesis strategy was adopted to effectively couple multiple sterically hindered N -methylated amino acids while suppressing epimerization. The total synthesis has enabled confirmation of the proposed absolute configuration of natural jahanyne.