np7b01025_si_007.cif (554.91 kB)
Structurally Diverse Diterpenoids from Sandwithia guyanensis
datasetposted on 2018-03-01, 13:21 authored by Simon Remy, Florent Olivon, Sandy Desrat, Florent Blanchard, Véronique Eparvier, Pieter Leyssen, Johan Neyts, Fanny Roussi, David Touboul, Marc Litaudon
Bioassay-guided fractionation of an EtOAc extract of the trunk bark of Sandwithia guyanensis, using a chikungunya virus (CHIKV)-cell-based assay, afforded 17 new diterpenoids 1–17 and the known jatrointelones A and C (18 and 19). The new compounds included two tetranorditerpenoids 1 and 2, a trinorditerpenoid 3, euphoractines P-W (4–11), and euphactine G (13) possessing the rare 5/6/7/3 (4–7), 5/6/6/4 (8–11), and 5/6/8 (13) fused ring skeletons, sikkimenoid E (12), and jatrointelones J-M (14–17) possessing jatropholane and lathyrane carbon skeletons, respectively. Jatrointelones J (14) and M (17) represent the first naturally occurring examples of C-15 nonoxidized lathyrane-type diterpenoids. The structures of the new compounds were elucidated by NMR spectroscopic data analysis. The relative configuration of compound 16 and the absolute configurations of compounds 3–6 and 14 were determined by single-crystal X-ray diffraction analysis. In addition, jatrointelone K (15) was chemically transformed to euphoractine T (8) supporting the biosynthetic relationships between the two types of diterpenoids. Only compound 15 showed a moderate anti-CHIKV activity with an EC50 value of 14 μM. Finally, using a molecular networking-based dereplication strategy, several close analogues of 12-O-tetradecanoylphorbol-13-acetate (TPA), one of the most potent inhibitors of CHIKV replication, were dereplicated.
Sandwithia guyanensis Bioassay-guided fractionationtetranorditerpenoids 1EC 50 valuelathyrane carbon skeletonsJatrointelones JNMR spectroscopic data analysisTPAeuphactine Gjatrointelone Kjatrointelones J-MC -15 nonoxidized lathyrane-type diterpenoidsconfigurationStructurally Diverse Diterpenoidsring skeletonstetradecanoylphorbol -13-acetateSandwithia guyanensisanti-CHIKV activityCHIKV replicationeuphoractines P-W12- Obiosynthetic relationshipsnetworking-based dereplication strategychikungunya virustrinorditerpenoid 3euphoractine Tcompound 15trunk barkcompound 16sikkimenoid Esingle-crystal X-ray diffraction analysis14 μ M