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 MIC 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 (IC: 5.9 ± 0.1, 6.1 ± 0.2, 12.1 ± 0.4, and 18.7 ± 1.9 μM, respectively).