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 gamma-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 gamma-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 mu g/mL, respectively. Meanwhile, (+/-)-1, (+/-)-1, (+)-2, and (+/-) displayed significant anti-inflammatory activities (IC50: 5.9 +/- 0.1, 6.1 +/- 0.2, 12.1 +/- 0.4, and 18.7 +/- 1.9 mu M, respectively).