Five decades of endeavor towards total syntheses of grayanane diterpenoids

The grayanane diterpenoids are a large series of natural products mainly from Ericaceae plants that embrace distinct polycyclic carbon frameworks with various densely arranged functionalities and show appealing bioactivities. Due to their elegant molecular architectures and compelling bioactivities, substantial efforts have been paid by synthetic chemists to conquer these targets by the power of total synthesis over half a century. The densely arranged functionalities embedded in the polycyclic carbon frameworks of these natural products pose formidable synthetic challenges to many otherwise routine transformations, rendering these synthetic projects even tougher and more elusive. Herein, we briefly described the history, diverse structures, biosynthetic origin, and bioactivities of grayanane diterpenoids and comprehensively reviewed the accomplished total syntheses of these daunting targets basically in chronological order from 1972 to 2024.