Synthesis and biological evaluation of novel triptolide analogues for anticancer activity

Three types of novel triptolide analogues with 9,11-olefin (3–5), five-membered unsaturated lactam ring (6–7) or A/B cis ring junction (8–14) were synthesized. Although with 9,11-olefin instead of 9,11-β-epoxide, compound 4a was much more active than the parent natural triptolide (1) with the lowest IC₅₀ value of 0.05 nM for SKOV-3 cells, clearly challenging the traditional viewpoint on the necessity of 9,11-β-epoxide group of triptolide. In addition, structure–activity relationships for three classes of compounds were studied.