Skeleton Rearranged and Oxygenated <i>ent</i>‐Rosane Diterpenoids with Antiadipogenic Activity from <i>Euphorbia milii</i>

Comprehensive Summary Five 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 EC 50 value of 3.92 μmol/L with low cytotoxicity (IC 50 &gt; 89.54 μmol/L).