Unusual immunosuppressive pyridine-containing bisnor- (c₂₃), tetranor- (c₂₁) and pentanor- (c₂₀) sesterterpenoids from Tibetan Leucosceptrum canum

An unusual pyridine-containing sesterterpenoid, leucosceptrodine (1), and five new nor-leucosceptrane sesterterpenoids, including bisnor- (C-23, 2), tetranor- (C-21, 3) and pentanor- (C-20, 4-6) skeletons, were isolated from the leaves of Tibetan Leucosceptrum canum. Their structures including their absolute configurations were determined by extensive spectroscopic analyses and quantum chemical calculations. A single crystal of one epimer (5) was crystallized from a pair of inseparable epimers, and its structure including its absolute configuration was determined by X-ray crystallographic analysis. The immunosuppressive activities of compounds 1-4 with different potencies were evaluated by inhibiting the secretion of cytokines TNF-alpha and IL-6 in LPS-induced RAW264.7 macrophages.