Ent-atisane diterpenoids from Euphorbia wallichii and their anti-influenza A virus activity

The study entailed the investigation of the roots of Euphorbia wallichii, which resulted in the isolation of 29 ent-atisane diterpenoids (1–29), 14 of which were previously unknown. These previously undescribed ones were named euphorwanoids A–N (3–5, 7, 9, and 10–18). Various techniques, including comprehensive spectroscopic methods and calculated electronic circular dichroism, were employed to determine their molecular structures. Additionally, the absolute configurations of ten ent-atisane diterpenoids (1, 2, 5, 6, 8, 9, 11, 12, 14 and 16) were established through X-ray crystallographic analyses. All isolated compounds' potential to inhibit the influenza A virus in vitro were evaluated. Compounds 18, 20, and 24 exhibited notable antiviral activity against the A/Puerto Rico/8/1934 strain. Their effective concentrations for reducing viral activity (EC50 values) were found to be 8.56, 1.22, and 4.97 μM, respectively. An intriguing aspect of this research is that it marks the first instance of ent-atisane diterpenes displaying anti-H1N1 activity. Empirical NMR rules were established with Δδ to distinguish the R/S configurations of C-13 and C-16 in ent-atisanes.