Structural Elucidation and Biomimetic Synthesis of (±)-Cochlactone A with Anti-Inflammatory Activity

A pair
of new natural meroterpenoids, (±)-cochlactone A (1) possessing a bicyclo[4.4.0]­decane ring system with a γ-lactone
fragment, was isolated from Ganoderma cochlear. To
further confirm their absolute configurations, a high-yielding, one-step
biomimetic synthesis of (±)-cochlactone A (1) from
ganomycin C (3) was conducted. In addition, a new compound,
(±)-cochlactone B (2), featuring a bicyclo[3.3.1]­decane
fragment fused to a γ-lactone moiety was synthesized. Their
structures were determined using spectroscopic data, X-ray diffraction
crystallography, and electronic circular dichroism (ECD) analyses.
Furthermore, a plausible reaction mechanism for the formation of 1 and 2 was proposed. Compounds (+)-2 and (±)-2 showed inhibitory effects against Staphylococcus aureus with MIC50 values of 41.1
± 0.1 and 64.0 ± 2.6 μg/mL, respectively. Meanwhile,
(±)-1, (−)-1, (+)-2, and (±)-2 displayed significant anti-inflammatory
activities (IC50: 5.9 ± 0.1, 6.1 ± 0.2, 12.1
± 0.4, and 18.7 ± 1.9 μM, respectively).