Skeleton Rearranged and Oxygenated ent‐Rosane Diterpenoids with Antiadipogenic Activity from Euphorbia milii

Abstract

Comprehensive SummaryFive unreported and oxygenated ent‐rosane diterpenoids (ent‐RDs), Euphomillanols A—E (1—5), were isolated from Euphorbia milii. Among them, compounds 1 and 2 are unprecedented 7/7/6‐fused tricyclic 5,10‐seco‐ent‐RDs and possess a unique 11‐oxabicyclo[4.4.1]undeca‐1(10),5‐diene moiety, while 3 is characterized by a 1‐methyl‐6‐oxabicyclo[3.2.1]oct‐2‐ene motif of ring A. Their structures with absolute configurations were unambiguously determined by the extensive spectroscopic methods, X‐ray crystallography, and ECD calculation. Putative biosynthetic pathways for compounds 1—3 are proposed. All compounds exhibited antiadipogenic effects in 3T3‐L1 adipocytes, and the most potent compound 4 showed an EC50 value of 3.92 μmol/L with low cytotoxicity (IC50 > 89.54 μmol/L).