Discovery and biological evaluation of dispirocyclic and polycyclic ent-clerodane dimers from Isodon scoparius as novel inhibitors of Toll-like receptor signaling†
Abstract
Scoparicacids A–C (1–3), three novel ent-clerodane dimers with unprecedented dispirocyclic 6/6/5/6/6 and hexacyclic 6/6/5/6/5/6 ring systems, were isolated from Isodon scoparius. A biomimetic synthesis of 3 was achieved using a double aldol reaction to construct a 5/6/5 ring system in one step. 2 and 3 exhibited significant immunosuppression on the proliferation of B lymphocytes evoked by TLR signaling stimulation in a dose-dependent manner and significantly abrogated the downstream pathway of TLR7 signaling in B cells.