Fermentation of Illigera aromatica with Clonostachys rogersoniana producing novel cytotoxic menthane-type monoterpenoid dimers

Illigera aromatica , a medicinal liana, was fermented with Clonostachys rogersoniana . Two novel menthane-type monoterpenoid dimers, dimericilligerates E ( 1 ) and F ( 2 ) were isolated from the fermented material. Their structures were identified by 1D/2D NMR, electric circular dichroism, derivatization, and Mosher's method. A novel elimination reaction that formed a benzene ring from a menthane moiety afforded derivative 1a , which possesses more resolved NMR signals than the dimeric monoterpenoid, dimericilligerate E ( 1 ). The determination of 1a verified the estimation of 1 . Compounds 1 and 2 showed potent cytotoxic activities; especially, 1 possessed significant activities against the liver hepatocellular carcinoma cell line (SMMC-7721) with an IC 50 value of 3.89 ± 0.23 μM. Three novel precursors, dimericilligerates A–C ( 3–5 ), were identified by HPLC-MS and isolated from the original I. aromatica . This paper presents a novel class of monoterpenoid dimers and suggests that C. rogersoniana -fermented I. aromatica is effective to produce cytotoxic dimeric monoterpenoids from inactive original materials.