Asymmetric total synthesis and anti-hepatocellular carcinoma profile of enantiopure euphopilolide and jolkinolide E

A flexible asymmetric synthesis of both enantiomers of euphopilolide (1) and jolkinolide E (2) [(+)-and (-)-1, (+)-and (-)-2] has been accomplished. This synthesis features an intramolecular oxa-Pauson-Khand reaction (oPKR) to expeditiously construct the challenging tetracyclic [6.6.6.5] abietane-type diterpene framework, elegantly showcasing the complexity-generating features of o-PKR synthetic methodology leveraging on a judiciously chosen suitable chiral pool scaffold. Furthermore, the anti-hepatocellular carcinoma (HCC) activity of synthetic (-)-euphopilolide (1), (- )-jolkinolide E (2) and their analogues was evaluated. We found that (-)-euphopilolide (1) and (-)-jolkinolide E (2) inhibited the proliferation and induced apoptosis in HCC cells. These findings lay a good foundation for further pharmacology studies of abietane lactone derivatives and provide valuable insight for the development of anti-HCC small molecule drug of natural product origin.

Automated summary

A flexible asymmetric synthesis of both enantiomers of euphopilolide and jolkinolide E was successfully achieved utilizing an intramolecular oxa-Pauson-Khand reaction. Furthermore, the anti-hepatocellular carcinoma activity of the synthesized compounds was evaluated, showing significant effects and providing valuable insight for the development of anti-HCC small molecule drugs.