Anti-inflammatory Alkaloids, Papaversomni A, a Hexacyclic-Membered Morphinan, and Two Pairs of E/Z Nonseparable Stereoisomers, Papaversomni C and Sinoracutinal, from Papaver somniferum.

Five new alkaloids, including papaversomnis A-C (1, 3, and 4), sinoracutinal (5), and ethoxyepiglaudine (6), along with two known alkaloids, 2 and 7, were discovered from Papaver somniferum. 1 has unprecedented 6/6/6/6/5/5-fused hexacyclic framework, representing a novel type of morphinan, whereas 4 and 5 are two pairs of E/Z nonseparable stereoisomers. Their stereochemistries were identified via single crystal X-ray diffraction analysis, the exciton chirality method evaluation of ECD, comparison of the experimental and calculated 1H and 13C NMR, and ECD data. 1 and 2 exhibited stronger anti-inflammatory effects on NO production in lipopolysaccharide-stimulated RAW 264.7 macrophages, with IC50 values of 16.63 ± 0.83 and 12.78 ± 0.95 μM, respectively, than the positive control, with IC50 value of 22.10 ± 0.63 μM. Western blotting analysis displayed that 1 and 2 could inhibit the expression of iNOS and COX-2 as key mediators in the inflammatory responses.