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

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Ryanodane diterpenes (RDs), complex plant natural products, show significant insecticidal and immunomodulatory activities by modulating ryanodine receptors (RyRs). Their limited natural supply drives synthetic efforts for drug discovery.

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Area of Science:

  • Natural Products Chemistry
  • Medicinal Chemistry
  • Organic Synthesis

Background:

  • Ryanodane diterpenes (RDs) are complex plant-derived compounds with unique pentacyclic structures.
  • Primarily found in Salicaceae and Lauraceae families, RDs exhibit potent bioactivities, including insecticidal and immunomodulatory effects.
  • Their primary target is the ryanodine receptor (RyR), crucial in muscle function and calcium signaling.

Purpose of the Study:

  • To provide a comprehensive review of natural ryanodane diterpenes (RDs) from 1948 to 2025.
  • To highlight the significance of RDs in drug discovery and development.
  • To emphasize the challenges posed by limited natural abundance and the progress in synthetic chemistry.

Main Methods:

  • Literature review of studies on ryanodane diterpenes (RDs) published between 1948 and May 2025.
  • Analysis of reported natural product isolation, structural elucidation, and biological activity data.
  • Survey of synthetic strategies and advancements in the total synthesis of RDs.

Main Results:

  • 135 natural RDs across nine subtypes have been identified since 1948.
  • RDs demonstrate significant insecticidal, cardiac, and immunomodulatory activities.
  • Synthetic chemistry has made substantial progress in constructing key RD scaffolds, overcoming natural abundance limitations.

Conclusions:

  • Ryanodane diterpenes (RDs) represent a promising class of natural products for drug discovery due to their potent bioactivities.
  • Advances in total synthesis are crucial for enabling further biological evaluation and therapeutic development.
  • Interdisciplinary collaboration is essential to fully realize the therapeutic potential of these complex molecules.