Seven-Step Synthesis of (±)-epi-Costunolide

Efficient Construction of (±)-epi-Costunolide through a Chromium(II)-Mediated Nozaki–Hiyama–Kishi Reaction: W. Dai, J. Zheng, X. Yan, W. Tang, L. Hu, Y. Zhang
Synlett 2021, 32, DOI: 10.1055/s-0040-1720348

Total synthesis of chiral natural compounds continues to represent an active area of research in organic chemistry. Costunolide is a germacrane sesquiterpene lactone widely found in the roots, barks, and leaves of a dozen of traditional medicinal herbs with a variety of pharmacological activities including anti-inflammatory, anti-bacteria, and anti-tumor. Recently, the group of Professor Yinan Zhang from the Nanjing University of Chinese Medicine (P. R. of China) reported an efficient synthesis of the title compound, which may be also viable for the synthesis of other germacrane sesquiterpenes.

Professor Zhang said: “To circumvent the drawbacks of previous methods in constructing the germacrane scaffold, a simple and scalable synthesis of (±)-epi-costunolide has been developed with the assistance of Nozaki–Hiyama–Kishi reaction. Although the stereochemistry only gives the epimer of the natural product, this strategy represents the simplest route (7 steps, 12% total yield) to reach the sesquiterpene lactone to date, providing an enabling synthetic strategy for future in-depth SAR and pharmacological mechanistic investigation of costunolide.”