Macrocyclic Decanor- (C₁₅) and Pentanor- (C₂₀) Sesterterpenoids and C₂₅ Precursor with Immunosuppressive Activity from <i>Leucosceptrum canum</i>

Phytochemical investigation on the leaves of <i>Leucosceptrum canum</i> led to the discovery of leucosceptrone A (<b>1</b>), a rearranged pentanor-leucosceptrane sesterterpenoid (C₂₀) with an unprecedented 6/9/5 tricyclic framework, and leucosceptrones B-E (<b>2</b>-<b>5</b>), three decanor-leucosesterterpane sesterterpenoids (C₁₅) and a C₂₅ biosynthetic precursor with two different unusual 10/5 bicyclic systems. Their structures were elucidated by extensive NMR spectroscopic analysis, quantum-chemical calculations, and X-ray diffraction analysis. A plausible biosynthetic route for these macrocyclic sesterterpenoids was proposed. Compounds <b>1</b> and <b>5</b> exhibited immunosuppressive activity by inhibiting the proliferation of T cells and the production of cytokine IFN-γ, and <b>5</b> was more active, with IC₅₀ values of 5.00 and 3.06 <i>μ</i>M, respectively.