Tsugaforrestolide, an Anti-Inflammatory Bisabolane-Type Sesquiterpene Lactone From the Vulnerable Conifer Tsuga forrestii.

In a previous phytochemical investigation, several structurally diverse diterpenoids were reported from the vulnerable relict conifer Tsuga forrestii (Forrest's hemlock). However, a previously undescribed co-occurring C-15 carboxylated bisabolane-type sesquiterpene (tsugaforrestolide, 1), featuring a 12,9-lactone moiety in its lateral chain, remained unreported. The chemical structure and absolute configuration of 1 were unambiguously elucidated through a combination of spectroscopic techniques, GIAO NMR calculations with DP4+ probability analysis, electronic circular dichroism (ECD) data, and single-crystal x-ray diffraction analysis. As the first sesquiterpenoid isolated from hemlock species, 1 exhibited pronounced anti-inflammatory activity, effectively inhibiting LPS-induced nitric oxide (NO) production in RAW 264.7 macrophages, with an IC50 value of 7.1 µM, comparable to the known inhibitor BAY11-7082 (IC50 = 8.7 µM). This finding further highlights the importance of conserving and sustainably utilizing this endangered plant species.