Rearranged Lindenane Sesquiterpenoid Trimers from Chloranthus fortunei: Target Discovery and Biomimetic Conversion.

Abstract

Seven lindenane-type sesquiterpenoid trimers, including four new ones (1-4) and three known analogues (5-7), were isolated from Chloranthus fortunei guided by high-performance liquid chromatography with photodiode array detection with characteristic absorption at 210 and 350 nm. Their structures, including absolute configurations, were achieved by high-resolution mass spectrometry, nuclear magnetic resonance, electronic circular dichroism, and quantum chemical calculations. Compound 1 was the first example of two lindenane units connected by a C-15-C-15' bond. The 5/7/5-fused ring system in 2 was presumably formed biogenetically by key keto-enol tautomerism and Cope rearrangement from 5. The 5/3/6 carbon skeleton in 3-5 and epi-cyclopropane in 3 and 6 might have originated from trishizukaol A (7) with a normal 3/5/6-fused ring system through vinylcyclopropane rearrangement. The biomimetic conversion from 7 to 3-6 was successfully achieved by adding a 365 nm ultraviolet lamp and a free radical initiator, and 2 was also spontaneously converted to 5 in methanol and CDCl3, which proved the correctness of the structural identification and the speculation described above. Compounds 1-7 exhibited anti-inflammatory activity with IC50 values in the range of 2.90-22.80 μmol/L.