Department of Applied Chemistry, Faculty of Science and Engineering, Chuo University, 1-13-27 Kasuga, Bunkyo-ku, Tokyo 112-8551, Japan.
J Org Chem. 2021 May 7;86(9):6787-6799. doi: 10.1021/acs.joc.1c00508. Epub 2021 Apr 20.
A stereocontrolled synthetic entry to the southern hemisphere C3-C17 acyclic domain of neaumycin B, a highly potent cytotoxic macrolide natural product, has been developed. The present synthesis is based on (i) a tandem olefin cross-metathesis/hemiacetalization/intramolecular oxa-Michael addition, (ii) a regioselective reductive acetal opening for differential protection of the C14 hydroxy group, (iii) a Horner-Wadsworth-Emmons reaction for the stereoselective formation of the C8-C9 olefin, and (iv) a Corey-Bakshi-Shibata asymmetric reduction to create the C7 stereogenic center.
已经开发出一种立体控制的合成方法，可用于合成新型霉素 B 的南半球 C3-C17 非环结构域，新型霉素 B 是一种具有高效细胞毒性的大环内酯天然产物。目前的合成方法基于：（i）串联烯烃交叉复分解/半缩醛化/分子内氧杂-Michael 加成；（ii）区域选择性还原缩醛开环，以实现对 C14 羟基的差异保护；（iii）Horner-Wadsworth-Emmons 反应，用于立体选择性地形成 C8-C9 双键；（iv）Corey-Bakshi-Shibata 不对称还原，以构建 C7 手性中心。
