Elsevier

Tetrahedron

Volume 70, Issue 41, 14 October 2014, Pages 7476-7483
Tetrahedron

Claoxylones A–I, prenylbisabolane diterpenoids with anti-Coxsackie B virus activity from the branches and leaves of Claoxylon polot

https://doi.org/10.1016/j.tet.2014.08.021Get rights and content

Abstract

Nine new prenylbisabolane diterpenoids, claoxylones A–I (19), were isolated from the branches and leaves of Claoxylon polot. This is the first example of prenylbisabolane diterpenoids with furan and tetrahydrofuran rings. Their structures and relative configurations were established by spectroscopic and conformational analysis, and the absolute configurations were determined by single-crystal X-ray diffraction and electronic circular dichroism (ECD) analysis. Compounds 19 exhibited antiviral activity against Coxsackie B3 virus, with IC50 values of 6.0–33.3 μM.

Introduction

Claoxylon A. Juss. is a genus comprising about 90 species confined to the tropics as trees or shrubs, of which five are present in China. Claoxylon polot (Burm.) Merr. (Euphorbiaceae) is a toxic shrub, 3–12 m tall, widely distributed in southwest China and used as a Chinese folk medicine commonly known as ‘diu liao bang’ for treating rheumatism, inflammation, and bleeding.1 Previous investigation of the leaves of C. polot yielded several triterpenoids.2 As part of an on-going program to study toxic medicinal plants for bioactive compounds with unusual structures, we have examined the EtOH extract of the dried branches and leaves of C. polot and succeeded in isolating nine new prenylbisabolane diterpenoids (19) (Fig. 1). Although several prenylbisabolane diterpenoids with long chains moieties have previously been reported in nature,3 and some of them showed cytotoxicity,3a antimalarial,3b and insecticidal activities,3e prenylbisabolane diterpenoids containing furan and tetrahydrofuran rings like those in 19 have not been previously reported from natural sources. Compounds 19 showed potent activities in vitro against the Coxsackie virus. Details of the isolation, structural elucidation, and bioactivities of these compounds are reported herein.

Section snippets

Results and discussion

Claoxylone A (1) was obtained as colorless needle-like crystals. The molecular formula was established as C20H26O6 by HRESIMS at m/z 363.1816 [M+H]+ (calcd 363.1802) and the NMR spectroscopic data (Table 1, Table 2), representing eight indices of hydrogen deficiency. The IR spectrum indicated the presence of hydroxy (3444 cm−1) and conjugated carbonyl groups (1667 cm−1). The 1H NMR spectrum exhibited two olefinic protons [δH 7.05 (s), 7.37 (s)], four methyls [δH 2.08 (3H, br s), 1.89 (3H, s),

Conclusions

In summary, nine new diterpenoids were isolated from the branches and leaves of C. polot. It is worthy of note that these prenylbisabolane diterpenoids with furan and tetrahydrofuran rings have not previously encountered in nature. Their configurations were determined by spin decoupling, JHMBC experiments, single-crystal X-ray diffraction, and electronic circular dichroism (ECD). Biologically, these new diterpenoids showed potent anti-Coxsackie B3 virus activity, especially, compounds 3 and 7

General experimental procedures

Melting points were determined on an XT5B (Beijing Keyi Electric Light Instrument Co., Ltd) micromelting point apparatus and are uncorrected. Optical rotations were measured on a JASCO P-2000 automatic digital polarimeter. UV spectra were obtained on a JASCO V650 spectrophotometer. IR spectra were recorded on a Nicolet 5700 FT-IR microscope instrument (FT-IR microscope transmission). 1D and 2D NMR spectra were recorded on Bruker Avance III-400, INOVA-500, Bruker Avance III-600, and Bruker

Acknowledgements

This project was supported by the National Science and Technology Project of China (No. 20012ZX09301002-002) and the National Natural Science Foundation of China (No. 21132009), and PCSIRT (No. IRT1007). We are grateful to the Department of Instrumental Analysis, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College for the IR, UV, NMR, and MS measurements and to the Instrumental Analysis Center of Beijing University of Chemical Technology for the

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