Synthesis of Jasplakinolide Analogues

Significance

Resin-bound azides 4 were prepared from Fmoc-protected β-amino acids 1 with 2-Cl-trityl-chloride resin through the solid-phase peptide synthesis and amide bond forming reactions. Cu(I)-catalyzed intermolecular 1,3-dipolar cycloaddition took place on resin and subsequent cleavage gave hydroxy/amino acids 6 in 70% overall yield (Method A). Acids 6 were subjected to Yamaguchi cyclization conditions to give the target compounds 8 in 5-59% yield. The tetrapeptide moieties of precursors 4 were cleaved from the resin support, and the resulting carboxylic acids were converted into terminal azidoalkynes 7 in 50-82% yield (Method B). Then the Cu(I)-catalyzed intramolecular alkyne azide reaction of the released azidoalkynes 7 proceeded to give macro­cyclic compounds 8 in 52-92% yield.