Systemic Study on the Biogenic Pathways of Yezo’otogirins: Total Synthesis and Antitumor Activities of (±)-Yezo’otogirin C and Its Structural Analogues

A systematic
study of the biomimetic pathways to yezo’otogirin
C under aerobic and anaerobic conditions has been investigated, and
both are found to be feasible pathways to the natural product depending
on the physiological conditions. Because of the lower activation energy,
the aerobic process would be more favorable when the in vivo oxygen
level is high. In the course of this study, a highly efficient synthetic
route to (±)-yezo’otogirin C has been established in four
steps (31% overall yield) from a readily available compound without
using any protecting groups. The natural product and its structural
analogues exhibited antitumor activities against several human cancer
cell lines and appeared to arrest cell cycles in different phases.

本研究系统考察了好氧与厌氧条件下合成雪鬼草素C（yezo’otogirin C）的仿生路径，结果表明两类路径均依赖生理状态，均可作为该天然产物的可行合成方案。由于活化能更低，当体内氧浓度较高时，好氧合成路径更具优势。本研究中，我们以易得原料出发，无需使用任何保护基，通过四步反应构建了外消旋雪鬼草素C（(±)-yezo’otogirin C）的高效合成路线，总产率达31%。该天然产物及其结构类似物对多株人癌细胞系展现出抗肿瘤活性，且可使细胞周期阻滞于不同时相。