Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
J Nat Prod. 2021 Jun 25;84(6):1854-1859. doi: 10.1021/acs.jnatprod.1c00339. Epub 2021 Jun 3.
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.
具有强细胞抑制活性的 yaku'amide B () 是一种高度不饱和的线性十三肽。在我们对 /-异构体的合成研究中，α,β-去氢异亮氨酸，一个意想不到的反醛醇反应进行，分别将 /-异构体,, 和 转化为,, 和 /, 。化合物,, 和 在残基-1 处具有甘氨酸而不是β-羟基异亮氨酸，并且在 中残基-8 的β-羟基缬氨酸进一步被甘氨酸取代。对 MCF-7 细胞生长抑制活性的评估表明， 比等效的 -和 -弱约 10 倍，表明在残基-8 处具有大侧链的重要性。
