A new secoiridoid glycoside from the fruits of Cornus officinalis (Cornaceae)

Abstract A new secoiridoid glycoside, 7β-O-dimethyl butanedioate morroniside (1) was isolated from the fruits of Cornus officinalis (Cornaceae) along with the known compound, caffeoyltartaric acid dimethyl ester (2) which was isolated from the family Cornaceae for the first time. Their structures were elucidated by physical and spectroscopic data analysis, including 1D and 2D NMR, ESI-MS and CD experiments. Graphical Abstract


Introduction
The Cornaceae, also known as the dogwood family, includes the genera of Aucuba, Cornus, Curtisia, Griselinia, Helwingia, Mastixia, Melanophylla, and Toricellia (Mabberley 1987). In particular, the genus Cornus is a rich source of iridoid glycosides (He et al. 2014). Cornus officinalis Sieb. et Zucc., a deciduous tree, is indigenous to eastern Asia and it is widely distributed in Korea, China and Japan (Jeong et al. 2012). Fruits of C. officinalis were reported to have various pharmacological activities such as anti-inflammatory Wei et al. 2013), cytotoxic and anti-oxidant (Savikin et al. 2009), anti-antibacterial (Kim & Kwak 1998), antidiabetic (Ma et al. 2012), neuroprotective (Jeong et al. 2012), and anti-dementia effects (Youn et al. 2013). Phytochemical researches on this plant have been reported on the isolation of more than 150 natural constituents, including iridoid glycosides (Jeong et al. 2012), secoiridoid glycosides (Jeong et al. 2012), bisiridoid glycosides (Jiang et al. 2011), triterpenoids (Jeong et al. 2012), flavonoids (Xie et al. 2012), phenolic compounds (Lin et al. 2011) and organic acids (Miyazawa et al. 2003). As a part of ongoing study to find new active compounds from the fruits of C. officinalis, a new compound, 7β-O-dimethyl butanedioate morroniside (1) was isolated along with caffeoyltartaric acid dimethyl ester (2) which was isolated from the family Cornaceae for the first time. Herein, the structure of 1 was elucidated by physical and spectroscopic data analysis (Figure 1).
Compound 1 had very similar structure to that of the previously isolated natural product, morroniside, except for the presence of a dimethyl butanedioate in 1. Usually, morroniside derivatives have been found to naturally occur as the mixture of 7α-and 7β-forms, however 1 was clearly isolated as the 7β-isomer in the present study. To the best of our knowledge, this is the first report on the secoiridoid class containing the butanedioate dimethyl ester functionality which has been rarely found in nature, although malic acid and dimethyl malate were previously reported (Miyazawa et al. 2003). on the other hand, the dimethyl group of 1 could be produced by MeoH extraction procedure. However, this doubt about 1 as an artefact can be removed because the possible precursor of 1, 7β-O-butanedioate morroniside has not been isolated in this study as well as in the previous reports. In addition, structure of 1 includes morroniside and dimethyl malate which have been previously isolated from this plant, providing strong evidence for the naturally occurring compound 1. Due to its limited amount available, a reinvestigation on the identification of 1 from this plant material by extraction with different organic solvents cannot be attempted.

General
optical rotations were measured with a JASCo P-1010 polarimeter. Circular dichroism measurements were performed using JASCo J-715 CD/oRD spectropolarimeter. 1D and 2D NMR spectra were obtained by a Bruker Advance 700 MHz spectrometer and a Varian Unity INoVA 400-MHz FT-NMR instrument, using Me 4 Si as internal standard and CD 3 oD as solvent. HRESIMS was carried out in the positive ion mode on a Waters ACQUNITY UPLC system coupled to a Micromass Q-Tof Micro mass spectrometer and an Agilent 6220 Accurate-Mass ToF LC/MS system. Silica gel (Sio 2 , 70-230 mesh and 230-400 mesh; Merck, Germany), YMC Gel oDS-A (12 nm, S-150 μm; YMC, Japan) and Sephadex LH-20 (GE Healthcare Bio-Sciences AB, UK) were used for column chromatography. TLC plates were silica gel 60 F 254 and RP-18 F 254S silica-gel (Merck, Germany). The spots were observed under UV light and visualized by spraying with 10% aq. H 2 So 4 solution followed by heating at 120 for 5 min.

Plant material
The dried seedless fruits of C. officinalis were purchased in January 2013 from Nonglim oriental Herbal Market in Seoul, Korea and identified by Prof. Je-Hyun Lee (College of oriental Medicine, Dongguk University, Korea). A voucher specimen (No. EA336) was preserved in the Natural Product Chemistry Laboratory, College of Pharmacy, Ewha Womans University, Korea.

Conclusions
There have been reports that the main constituents of C. officinalis, loganin and morroniside (each 1.2% w/w) showed various biological activities such as anti-inflammatory (Lee et al. 1995;Park et al. 2010;Wei et al. 2013), anti-oxidant (Xu et al. 2006), antidiabetic (Yokozawa et al. 2008;Yamabe et al. 2010), and neuroprotective (Kwon et al. 2009;Wang et al. 2010), and anti-dementia effects (Youn et al. 2013). Since these main constituents are responsible for significant portions in quantity and biological activities, researches for isolation of their new derivatives have been pursued. In this study, 7β-O-dimethyl butanedioate morroniside (1) was identified as a new morroniside derivative, but not further subjected to the biological evaluation due to the limited amount available. The isolation of caffeoyltartaric acid dimethyl ester (2) from the family Cornaceae is reported herein for the first time.

Disclosure statement
No potential conflict of interest was reported by the authors.