Antiviral chlorinated daphnane diterpenoid orthoesters from the bark and wood of Trigonostemon cherrieri

The chemical investigation of the bark and wood of Trigonostemon cherrieri (Euphorbiaceae) led to the isolation of ten chlorinated daphnane diterpenoid orthoesters (DDO) named trigocherrins A–F (1–6) and trigocherriolides A–D (7–10). Several DDO exhibited strong antiviral activity against chinkungunya, Sindbis and Semliki forest virus. [Display omitted] ► Ten daphnane diterpenoid orthoesters were isolated from Trigonostemon cherrieri. ► They all possess a mono- or dichlorovinyl group on the daphnane core. ► They were isolated using bioassay-guided and LC/MS-guided fractionations. ► They are a class of non-nucleosidic inhibitor of the DENV NS5 RdRp. ► They showed strong antiviral activity against CHIK, Sindbis and Semliki forest virus. The chemical study of the bark and the wood of Trigonostemon cherrieri, a rare endemic plant of New Caledonia, led to the isolation of a series of highly oxygenated daphnane diterpenoid orthoesters (DDO) bearing an uncommon chlorinated moiety: trigocherrins A–F and trigocherriolides A–D. Herein, we describe the isolation and structure elucidation of the DDO (trigocherrins B–F and trigocherriolides A–D). We also report the antiviral activity of trigocherrins A, B and F (1, 2 and 6) and trigocherriolides A, B and C (7–9) against various emerging pathogens: chikungunya virus (CHIKV), Sindbis virus (SINV), Semliki forest virus (SFV) and dengue virus (DENV).