Immunomodulatory Constituents of (Snake Liverwort) and the Relationship of Isolepidozenes to Germacranes and Humulanes.

Structural elucidation of three new sesquiterpenoids, namely, (1,4)-lepidoza-1(10),4-dien-14-ol (), -(1(10),4,5,7)-germacra-1(10),6 diene-11,14-diol (), and -(1(10),4,5,7)-humula-1(10),5-diene-7,14-diol (), isolated from the liverwort , was accomplished by a combination of extensive NMR experiments, H NMR simulation, and other means. Additionally, the change of the identity of bicyclogermacren-14-al, previously reported as a constituent, to isolepidozen-14-al is proposed. Compounds and appear to be related to via hydration involving a shared intermediate, a substituted cyclopropylmethyl cation, formed by a highly regio- and stereoselective protonation of , followed by a stereospecific fission of the three-membered ring. In other words, an isolepidozene derivative might be a branchpoint to humulanes and germacranes; this transformation could be of, up to now, unknown, biosynthetic and/or synthetic relevance. Multivariate statistical analysis of the compositional data of extract constituents was used to probe the hypothesized biochemical relations. The immunomodulatory effect of - and conocephalenol () was evaluated in an in vitro model on both nonstimulated and mitogen-stimulated rat splenocytes. The compounds displayed varying degrees of cytotoxicity to nonstimulated splenocytes, whereas and were found to exert immunosuppressive effects on concanavalin A-stimulated splenocytes while not being cytotoxic at the same concentrations.