Structurally Diverse Monocarbocyclic Sesterterpenoid Biosynthetic Intermediates from Colquhounia coccinea var. mollis with Immunosuppressive and Antiadipogenic Activity.

Sesterterpenoids with monocarbocyclic skeletons are key biosynthetic intermediates but are rarely isolated in plants. Herein, we report the discovery of 31 plant-derived monocarbocyclic sesterterpenoids, precolquhounoids, from the Lamiaceae shrub Colquhounia coccinea var. mollis. These isolates exhibit remarkable structural diversity, encompassing α-ketol regioisomers, spirolactone-containing stereoisomers, and highly oxidized frameworks featuring a uniquely fused 1,3-dioxolane core. The unambiguous stereochemical assignment of these highly flexible molecules employed an integrated structural elucidation strategy combining extensive NMR spectroscopic analysis, single-crystal X-ray diffraction, the modified Mosher's method, and TDDFT ECD calculations. Biogenetically, these diverse monocarbocyclic isolates serve as pivotal missing links, providing crucial insights into the divergent biosynthetic cascades that generate the complex 5/6/5-fused tricyclic architecture of colquhounoids. Furthermore, biological evaluations revealed that several of these novel precolquhounoids exhibit promising immunosuppressive (compound 6, IC50 = 9.81 ± 1.86 μM) and antiadipogenic activities.