3,4- Seco -Isopimarane Diterpenes from the Twigs and Leaves of Isodon Flavidus .

Three isopimarane diterpenes [fladins B ( 1 ), C ( 2 ), and D ( 3 )] were isolated from the twigs and leaves of Chinese folk medicine, Isodon flavidus . The chemical structures were determined by the analysis of the comprehensive spectroscopic data, and the absolute configuration was confirmed by X-ray crystallographic analysis. The structures of 1 - 3 were formed from isopimaranes through the rearrangement of ring A by the bond break at C-3 and C-4 to form a new δ -lactone ring system between C-3 and C-9. This structure type represents the first discovery of a natural isopimarane diterpene with an unusual lactone moiety at C-9 and C-10. In the crystal of 1 , molecules are linked to each other by intermolecular O-H···O bonds, forming chains along the b axis. Compounds 1 - 3 were evaluated for their bioactivities against different diseases. None of these compounds displayed cytotoxic activities against HCT116 and A549 cancer cell lines, antifungal activities against Trichophyton rubrum and T. mentagrophytes , or antiviral activities against HIV entry at 20 µg/mL (62.9-66.7) µM. Compounds 1 and 3 did not show antiviral activities against Ebola entry at 20 µg/mL either; only 2 was found to show an 81% inhibitory effect against Ebola entry activity at 20 µg/mL (66.7 µM). The bioactivity evidence suggested that this type of compound could be a valuable antiviral lead for further structure modification to improve the antiviral potential.