Three Unusual Sesquiterpenes with Distinctive Ring Skeletons from Daphne penicillata Uncovered by Molecular Networking Strategies

Daphnenoids A–C ( 1 – 3 ), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D ( 4 ) were obtained from the herb of Daphne penicillata by molecular networking strategies. Daphnenoid A ( 1 ) possesses a unique caged tetracyclo [5.3.2.0 1, 6 .0 4, 11 ] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C ( 2 and 3 ) were the first discovered natural sesquiterpenes with unique 5/5 spirocyclic systems in nature. Their structures were determined by NMR spectroscopic analysis, computer-assisted structure elucidation methods, quantum chemical calculations, and X-ray diffraction. A hypothetical biogenetic pathway begins with typical guaiane sesquiterpene ( a ), including a key intermediate ( 4 ) was proposed. Daphnenoids B and C ( 2 and 3 ) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.