Ryanodane diterpenes: occurrence, structural diversity, bioactivities, and synthesis

Covering: 1948 to 2025Ryanodane diterpenes (RDs) are a unique class of plant-derived natural products characterized by their complex, polyoxygenated pentacyclic frameworks. They have been primarily identified in plants from the Salicaceae and Lauraceae families. In recent years, RDs have garnered significant interest due to their notable bioactivities, particularly their modulation of ryanodine receptors (RyRs) and their insecticidal properties. Since the initial isolation of ryanodine from the shrub Ryania speciosa Vahl in 1948, a total of 135 natural RDs across nine subtypes have been discovered. These compounds exhibit a range of biological activities, including insecticidal, cardiac activity, and immunomodulatory effects. However, the limited natural abundance of RDs has posed challenges for their comprehensive biological evaluation. Fascinated by their high affinity for RyRs and their intricate polycyclic structures, synthetic chemists have pursued the total synthesis of RDs since the 1990s, with notable progress in recent decades. Advances in synthetic methodology have enabled the successful construction of key RD scaffolds, facilitating further exploration of their biological potential. This review provides a comprehensive overview of RDs from 1948 to May of 2025, highlighting their significance in drug discovery and development. It also emphasizes the need for interdisciplinary collaboration to fully harness the therapeutic potential of these complex natural products.