Three Unusual Sesquiterpenes with Distinctive Ring Skeletons from <i>Daphne penicillata</i> Uncovered by Molecular Networking Strategies

Abstract

Daphnenoids A-C (<b>1</b>-<b>3</b>), three unusual sesquiterpenes with distinctive ring skeletons, together with a biogenetically related daphnenoid D (<b>4</b>) were obtained from the herb of <i>Daphne penicillata</i> by molecular networking strategies. Daphnenoid A (<b>1</b>) possesses a unique caged tetracyclo [5.3.2.0¹,⁶.0⁴,¹¹] dodecane scaffold by unexpected cyclizations of C-1/C-11 and C-2/C-14. Daphnenoids B and C (<b>2</b> and <b>3</b>) 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 (<b>a</b>), including a key intermediate (<b>4</b>) was proposed. Daphnenoids B and C (<b>2</b> and <b>3</b>) exhibited potential inhibitory activities on the production of NO against LPS-induced BV2 microglial cells.