Vlasouliolides A-D, four rare C17/C15 sesquiterpene lactone dimers with potential anti-inflammatory activity from Vladimiria souliei

Li-Ping Chen,Yun-Heng Shen,Jian-Ping Zhang,Hui-Liang Li,Guo-Zhen Wu,Qing-Xin Liu,Wei-Dong Zhang,Ji Ye

doi:10.1038/srep43837

Abstract

Vlasouliolides A-D (1–4), four rare sesquiterpene lactone dimers, were isolated from Vladimiria souliei. The common structural characteristic of 1–4 is the C32 skeleton comprising two sesquiterpene lactone units linked by a C11-C13′ single bond with one acetyl connected to the C-13 position of one of the two sesquiterpene lactone units. The stereochemistries of 1–4 were assigned by a combination of NOESY correlations and Cu-Κα X-ray crystallographic analyses. Compounds 1–4 strongly inhibited the production of NO in LPS-stimulated RAW 264.7 cells. Furthermore, 1 and 2 inhibited the activation of NF-κB in LPS-induced 293T cells.

Highlights

Occurring sesquiterpene lactone dimers (SLDs) are a type of complex found in natural products with many pharmacological activities[1,2]
Sesquiterpenes, as major constituents isolated from the Vladimiria species, possess various types of structures including guaianolide, carabrane, eudesmane and germacrane sesquiterpenes[8,9,10,11,12]
In the course of our investigation on structurally novel SLDs from the family of Asteraceae, four rare SLDs with C32 cores were discovered from Vladimiria souliei, and they were designated vlasouliolides A-D (1–4) (Fig. 1)

Summary

Results and Discussion

The HMBC spectrum of 1 showed the key correlations of four typical terminal alkylene groups (Fig. 2A), including H2-14/C-1 and C-9; H2-15/C-3 and C-5; H2-14′/C-1′and C-9′;and H2-15′/C-3′and C-5′.subunits A and B were deduced to be two guaianolide moieties similar to dehydrocostus lactone[14,15]. The relative configuration of subunit B was deduced by analysis of the NOESY correlations (Fig. 4A). The structure of 3 was elucidated as shown, and the absolute configuration was assigned as 1R, 5R, 6S, 7S, 11S, 5′S, 6′S, 7′S, 10′S, 11′Sby Cu-Κα X-ray crystallographic analysis (Fig. 4B) The structure of 3 was elucidated as shown in Fig. 1, and the absolute configuration was assigned as 1R, 5R, 6S, 7S, 11S, 5′S, 6′S, 7′S, 10′S, 11′Sby Cu-Κα X-ray crystallographic analysis (Fig. 4B)

Vlasouliolide same molecular

Methods

Author Contributions

Additional Information