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

Abstract

Phytochemical investigation on the leaves of Leucosceptrum canum led to the discovery of leucosceptrone A (1), a rearranged pentanor-leucosceptrane sesterterpenoid (C₂₀) with an unprecedented 6/9/5 tricyclic framework, and leucosceptrones B–E (2–5), 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 1 and 5 exhibited immunosuppressive activity by inhibiting the proliferation of T cells and the production of cytokine IFN-γ, and 5 was more active, with IC₅₀ values of 5.00 and 3.06 μM, respectively.