Generation and Biological Evaluation of Degraded Derivatives of the Three /-Isomers of Yaku'amide B.

Potently cytostatic yaku'amide B () is a highly unsaturated linear tridecapeptide. During our synthetic studies of the /-isomers of the α,β-dehydroisoleucines of , an unexpected retro-aldol reaction proceeded to transform /-isomers , , and into , , and /, respectively. Compounds , , and have a glycine at residue-1 instead of β-hydroxyisoleucine, and the β-hydroxyvaline at residue-8 in is further replaced by glycine in . Evaluation of the growth inhibition activities against MCF-7 cells revealed that was approximately 10-fold weaker than the equipotent - and -, demonstrating the biological importance of a bulky side chain at residue-8.