np1c00339_si_001.pdf (1.85 MB)
Download fileGeneration and Biological Evaluation of Degraded Derivatives of the Three E/Z‑Isomers of Yaku’amide B
journal contribution
posted on 03.06.2021, 07:44 authored by Koichi Kamiya, Hiroaki Itoh, Masayuki InouePotently cytostatic yaku’amide
B (1) is a highly
unsaturated linear tridecapeptide. During our synthetic studies of
the E/Z-isomers of the α,β-dehydroisoleucines
of 1, an unexpected retro-aldol reaction proceeded to
transform E/Z-isomers 2, 3, and 4 into 2a, 3a, and 4a/4b, respectively. Compounds 2a, 3a, and 4a have a glycine at
residue-1 instead of β-hydroxyisoleucine, and the β-hydroxyvaline
at residue-8 in 4a is further replaced by glycine in 4b. Evaluation of the growth inhibition activities against
MCF-7 cells revealed that 4b was approximately 10-fold
weaker than the equipotent 2–4 and 2a–4a, demonstrating the biological importance
of a bulky side chain at residue-8.