(±)-Japonones A and B, two pairs of new enantiomers with anti-KSHV activities from Hypericum japonicum.

Linzhen Hu,Hua Li,Hucheng Zhu,Weiguang Sun,Jianping Wang,Junjun Liu,Zengwei Luo,Lei Li,Jinfeng Huang,Yonghui Zhang,Yu Zhang,Yongbo Xue

doi:10.1038/srep27588

Abstract

Two pairs of new enantiomers with unusual 5,5-spiroketal cores, termed (±)-japonones A and B [(±)-1 and (±)-2], were obtained from Hypericum japonicum Thunb. The absolute configurations of (±)-1 and (±)-2 were characterized by extensive analyses of spectroscopic data and calculated electronic circular dichroism (ECD) spectra, the application of modified Mosher’s methods, and the assistance of quantum chemical predictions (QCP) of 13C NMR chemical shifts. Among these metabolites, (+)-1 exhibited some inhibitory activity on Kaposi’s sarcoma associated herpesvirus (KSHV). Virtual screening of (±)-1 and (±)-2 were conducted using the Surflex-Dock module in the Sybyl software, and (+)-1 exhibited ability to bind with ERK to form key interactions with residues Lys52, Pro56, Ile101, Asp165, Gly167 and Val99.

Highlights

Hypericum japonicum Thunb, an annual herbaceous plant of the genus Hypericum (Hypericaceae), widely distributed in Asia, Oceania, and North America, has been historically used for the treatment of hepatitis, tumors, and gastrointestinal disorder in Chinese traditional medicine[1,2]
In our continuous investigations of structurally unique and biologically active organic substances from the genus Hypericum, a substantial number of phloroglucinol derivatives were obtained from H. sampsonii, H. ascyron, and H. attenuatum[8,9,10]
The aerial parts of H. japonicum (30 kg) were dried naturally and immersed in 95% EtOH for three weeks at 25 °C to afford a brown syrup (0.75 kg), which was successively extracted with petroleum ether and chloroform against water

Summary

Introduction

Hypericum japonicum Thunb, an annual herbaceous plant of the genus Hypericum (Hypericaceae), widely distributed in Asia, Oceania, and North America, has been historically used for the treatment of hepatitis, tumors, and gastrointestinal disorder in Chinese traditional medicine[1,2]. Our sustained interest in this genus led to the discovery of two pairs of new 1,6-dioxaspiro[4.4]non-2-en-4-one enantiomers (i.e., (±)-japonones A and B) (Fig. 1) from the aerial parts of H. japonicum. The structural connectivity of 1 was established by analyses of its 1H − 1H COSY and HMBC spectra aided by its HSQC spectrum (Fig. 2).

Results

Conclusion