Natural promising daphnane diterpenoids: An integrated review of their sources, structural classification, biological activities, and synthesis

Daphnane diterpenoids, as one of the representative types of diterpenoid compounds with rich structural diversity and significant biological activities, have an uncommon 5/7/6 tricyclic skeleton mainly found in species of Thymelaeaceae and Euphorbiaceae families. Due to the unique peculiarity of the framework and remarkable pharmacological activities, over the past three decades, novel structures have been continuously discovered and more structural subtypes have been derived. However, there is always a lack of a unified and convincing structural classification strategy for the summary of daphnane diterpenoids, which affects the in-depth and systematic research of pharmaceutical chemists and pharmacologists. In addition, the distinctive skeleton, continuous chiral centers, and prominent bioactivities of daphnane diterpenoids have attracted widespread interest among synthetic chemists. However, there are currently only a few reports of complete synthesis of compounds with low overall yields. Given the broad attention paid to daphnane diterpenoids in recent years, this review summarized the sources, structural classification, biological activities, and synthesis of around 300 natural daphnane diterpenoids discovered from 1993 to 2023, providing a reference for further discovery of novel structures, chemical and biological synthesis, and drug research.