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Synthesis of Jasplakinolide Analogues
T.-S. Hu, R. Tannert, H.-D. Arndt, H. Waldmann*
Universität Dortmund and Max-Planck-Institut für Molekulare Physiologie, Dortmund, Germany
22 November 2007 (online)
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.