Crotofolane Diterpenoids: Structural Diversity, Natural Sources, and Therapeutic Potential

Crotofolanes are an unusual class of diterpenoid family, which are distinguished by a unique fused tricyclic 5/6/7-ring skeleton, primarily reported from Croton genus (Euphorbiaceae). This work comprehensively summarizes the reported crotofolanes, including their sources, structural classifications, biosynthesis, and biological activities. A total of 62 crotofolane derivatives have been isolated from 11 Croton species in the period from 1975 to April 2025. Some crotofolanes possess notable biological properties such as anti-HIV, antimalarial, cytotoxic, and immunosuppressive. The review also emphasizes the distinct oxidative changes and rearrangements that result in structural variation among crotofolanes.