A new lignan from Schefflera arboricola

Abstract

A new lignan, arborlignan A, along with five known substances, neoechinulin A, 4-hydroxy-3,5-dimethoxybenzaldehyde, 3,3′-dimethoxy-4,4′-dihydroxystilbene, β-hydroxypropiovanillone, and coniferyl aldehyde, are isolated from Schefflera arboricola. Their structures are elucidated by mass spectrometry and nuclear magnetic resonance spectroscopy experiments and by comparison with literature data. These compounds are isolated from the genus Schefflera for the first time.

Introduction

Schefflera arboricola (Araliaceae), a spineless tree or shrub, is widely distributed in tropical and subtropical areas, mainly in the southwest and southeast regions of China. ¹ Several species of this genus are widely used in traditional medicine, such as S. delavayi and S. leucantha.^2–4 The main phytochemical constituents reported from S. arboricola were triterpenoids, steroids, sesquiterpenoids, organic acids, benzyl glycosides, lignans, quinones, and diterpenes.^5–7 Previous bioactivity studies have confirmed their medicinal properties as analgesic, anti-inflammatory, antitumor, antibacterial, antiviral, and anti-allergic.^8–10 As part of our continuing efforts to search for bioactive compounds derived from Schefflera, a new lignan, arborlignan A (1) along with five known substances, neoechinulin A (2), ¹¹ 4-hydroxy-3,5-dimethoxybenzaldehyde (3), ¹² 3,3′-dimethoxy-4,4′-dihydroxystilbene (4), ¹³ β-hydroxypropiovanillone (5), ¹⁴ and coniferyl aldehyde (6), ¹⁵ are obtained from S. arboricola. Herein, the isolation and structure characterization of these compounds are presented.

Results and discussion

Arborlignan A (1) is obtained as a colorless oil, and has the molecular formula C₂₁H₂₄O₈, as determined by high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) (m/z 405.1541 [M + H]⁺, calcd for 405.1544), corresponding to 10 degrees of unsaturation. The optical rotation value is ${[\alpha ]}_D^{25}$ 33.33 (c 0.05 mg/mL, MeOH). Ultraviolet (UV) absorptions (λ_max (log ε) in MeOH) are observed at 207 (0.69) and 276 (0.19) nm. The infrared (IR) absorptions at 3392, 2947, 2835, 1450, and 1030 cm^−m indicate the presence of hydroxy, =C–CH₂, –CH₂, benzene and ether bonds, respectively.

The ¹H nuclear magnetic resonance (NMR) spectrum of compound 1 displays four aromatic protons at δ_H 6.70 (s, H-2′, H-6′), δ_H 6.97 (brs, H-2), δ_H 6.99 (brs, H-6) in the downfield region, indicating the presence of two tetrasubstituted benzenes. Two olefinic protons at δ_H 6.56 (dt, J = 15.8, 1.5 Hz, H-7) and 6.25 (dt, J = 15.8, 5.9 Hz, H-8), and one methylene at δ_H 4.22 (dd, J = 5.9, 1.5 Hz, H2-9), form the allyl segment. In addition, the large coupling constant between H-7 and H-8 (J_7,8 = 15.8 Hz) reveals the trans-configuration of the double bond (Table 1). The downfield region of the ¹³C NMR spectrum shows 14 carbon signals at δ_C 149.4 (C-3′, 5′), 149.2 (C-5), 145.5 (C-3), 136.4 (C-4′), 133.8 (C-4), 132.6 (C-1), 132.0 (C-7), 130.3 (C-1′), 127.6 (C-8), 116.5 (C-6), 112.1 (C-2), and 104.1 (C-2′, 6′), corresponding to the two benzene rings and double bond in 1, which occupy nine of the 10 degrees of unsaturation. Meanwhile, four protons δ_H 5.55 (d, J = 6.3 Hz, H-7′), 3.52 (m, H-8′), 3.81 (overlapped, H-9′a), and 3.88 (dd, J = 11.0, 5.3 Hz, H-9′b) in the ¹H NMR spectrum indicate the presence of an epoxy propane group. This was confirmed from the ¹H-¹H COSY spectrum (Figure 1) and accounting for the remaining one degree of unsaturation. The above information implies that compound 1 is a lignan. The three -OMe groups resonating at δ_H 3.91 (3H, s, 3-OMe) and δ_H 3.83 (6H, s, 3′, 5′-OMe) are assigned to C-3 and C-3′, 5′, and this was confirmed by the HMBC cross-peaks from 3-OMe to C-3, and from 3′, 5′-OMe to C-3′, 5′ and by the NOESY cross-peaks of 3-OMe/H-2 and 3′, 5′-OMe/H-2′, 6′. Detailed analysis of the 1D and 2D NMR spectra of 1 suggest that the above two units of 1 are connected via a C-9−C-9′ ether linkage, with further evidence being provided by the molecular weight. Thus, the planar structure of 1 is established as depicted (Figure 2).

Table 1.

¹H NMR (500 MHz) and ¹³C NMR (125 MHz) data for 1 in CD₃OD.

	δH, mult, (J in Hz)	δC
1	–	132.6
2	6.97, brs	112.1
3	–	145.5
4	–	133.8
5	–	149.2
6	6.99, brs	116.5
7	6.56, dt, (15.8,1.5)	132.0
8	6.26, dt, (15.8,5.9)	127.6
9	4.22, dd, (5.9, 1.5)	63.9
1′	–	130.3
2′	6.70, s	104.1
3′	–	149.4
4′	–	136.4
5′	–	149.4
6′	6.70, s	104.1
7′	5.55, d, (6.3)	89.4
8′	3.52, m	55.3
9′a	3.81, overlapped	64.9
9′b	3.88, dd, (11.0, 5.3)	–
3-OMe	3.91, s	56.8
3′-OMe	3.83, s	56.7
5′-OMe	3.83, s	56.7

Figure 1.

Key ¹H-¹H COSY and HMBC correlations for 1.

Figure 2.

The structures of compounds 1–6.

Indeed, the right epoxide part of 1 is identical as 4-[3′-(hydroxymethyl)oxiran-2′-yl]-2,6-dimethoxyphenol, except the configuration of the epoxy group. ¹⁶ An larger coupling constant of 6.3 Hz indicates a trans-disubstituted epoxide,^17,18 which was confirmed by the analysis of the NOESY spectrum (Figure 3). Moreover, their optical rotations are different (1, ${[\alpha ]}_D^{25}$ 33.3; 4-[3′-(hydroxymethyl)oxiran-2′-yl]-2,6-dimethoxyphenol, ${[\alpha ]}_D^{26}$ −3.0), which suggest 1 has a 7′S,8′S configuration.^19–23 Therefore, the structure of 1 is assigned as a new lignan linked via a C-9−C-9′ ether, which is named as arborlignan A.

Figure 3.

Key NOESY correlations for 1.

The obtained known compounds (Figure 1) are characterized as neoechinulin A (2), 4-hydroxy-3,5-dimethoxybenzaldehyde (3), 3,3′-dimethoxy-4,4′-dihydroxystilbene (4), β-hydroxypropiovanillone (5), and coniferyl aldehyde (6), by comparison of their NMR and MS data with those reported in the literature.

Conclusion

To the best of our knowledge, compounds 1–6 have been isolated from the genus Schefflera for the first time. Among these isolated compounds, there are multiple skeleton types, including lignan, alkaloid, stilbene, phenylpropanoid, and phenolic. Importantly, the presence of this neolignan skeleton is the first report from the genus Schefflera and S. arboricola, which is different from previous tetrahydrofuran lignans.

Experimental section

General experimental procedures

UV spectra were obtained in MeOH using a Shimadzu PharmaSpectra UV-1800 instrument. IR spectra were measured on a Thermo Scientific Nicolet iS10 FTIR spectrometer. NMR experiments were conducted on a Bruker Avance III 500 spectrometer. Electron-impact mass spectrometry (EI-MS) was conducted on an Agilent 7890B-5977A. Electrospray ionization mass spectrometry (ESI-MS) was conducted on an Agilent 1200/6320 ion trap XCT LC-MS spectrometer. HR-ESI-MS were performed with an Agilent 6320 LC-Q TOF High Mass. Optical rotations were measured on a Rudolph AUTOPOL^® IV polarimeter. Silica gel (200−300 mesh, Qingdao Maine Chemical Factory), and Sephadex LH-20 (Amersham Biosciences) were used for column chromatography. Samples were made visual by spraying with 10% H₂SO₄/EtOH (v/v) followed by heating. Semipreparative high-performance liquid chromatography (HPLC) was conducted on an Agilent 1100 system using a YMC-Pack ODS C-18 (250 × 10 mm, 5 μm) column with a flow rate of 2 mL/min.

Plant material

The twigs and leaves of S. arboricola were purchased from Quanzhou Zhongqiao Co., Ltd pharmaceutical company in July 2016 in Fujian Province, China.

Extraction and isolation

The dried twigs and leaves of S. arboricola (20 kg) were powdered and extracted with 95% EtOH at 80 °C (three times, 3 h each time). The filtrate was concentrated under reduced pressure to afford a crude extract. This was extracted with petroleum ether, chloroform, ethyl acetate, and n-butanol. The chloroform-soluble fraction (68.9 g) was subjected to silica gel column chromatography, eluting with a gradient of CH₂Cl₂/EtOAc (from 50:1 to 1:1), to give nine fractions, Fr. 1–9. Fr. 3 was further separated on a silica gel column, eluting with a gradient of PE/EtOAc (from 50:1 to 2:1), to afford Fr. 3.1–3.5. Fr. 3.4 was subjected to silica gel column chromatography, eluting with a gradient of PE/acetone (from 7:1 to 1:1). Finally then compound 3 (6 mg) was obtained by recrystallization from Fr. 3.4.7. Fr. 3.5 was separated on several silica gel columns, eluting with gradients of PE/acetone and CH₂Cl₂/EtOAc to afford Fr. 3.5.1–3.5.5, and then Fr. 3.5.2 and Fr. 3.5.3 were applied to Sephadex LH-20 eluting with CH₂Cl₂/MeOH (1:1), respectively, to obtain compounds 5 (4 mg) and 6 (5 mg). Fr. 4 was separated on several silica gel columns, eluting with gradients of PE/EtOAc (from 30:1 to 1:1) and PE/acetone (from 9:1 to 1:1) to afford Fr. 4.3.1–4.3.5, then Fr. 4.3.2 was applied to a Sephadex LH-20 column eluting with CH₂Cl₂/MeOH (1:1) to give compound 4 (4 mg). Fr. 9 was subjected to an MCI gel column eluting with MeOH/H₂O (from 30% to 100%) to removal pigment and then was separated on an ODS column eluting with MeOH/H₂O (from 30% to 100%) to give nine subfractions, Fr. 9.1–9.9. Fr. 9.3 was subjected to silica gel column chromatography, eluting with a gradient of CH₂Cl₂/MeOH (from 6:1 to 1:1), then Fr. 9.3.7 was applied to a Sephadex LH-20 column eluting with CH₂Cl₂/MeOH (1:1), and further purified by HPLC (MeOH/H₂O, 50%, 43%) to afford 2 (4 mg, t _R 31.5 min) and 1 (3 mg, t _R 41 min).

Neoechinulin A (2): yellow crystals, ¹H and ¹³C NMR data (see Supplemental Tables S1 and S2). EI-MS: m/z = 323 [M]⁺.

4-Hydroxy-3,5-dimethoxybenzaldehyde (3): white crystals, ¹H and ¹³C NMR data (see Supplemental Tables S1 and S2). EI-MS: m/z = 182 [M]⁺.

3,3′-Dimethoxy-4,4′-dihydroxystilbene (4): white powder, ¹H and ¹³C NMR data (see Supplemental Tables S1 and S2). EI-MS: m/z = 272 [M]⁺.

β-Hydroxypropiovanillone (5): yellow oil, ¹H and ¹³C NMR data (see Supplemental Tables S1 and S2). ESI-MS: m/z = 197 [M + H]⁺.

Coniferyl aldehyde (6): white solid, ¹H and ¹³C NMR data (see Supplemental Tables S1 and S2). ESI-MS: m/z = 201.1 [M + Na]⁺.

Supplemental Material

supporting_information – Supplemental material for A new lignan from Schefflera arboricola

Supplemental material, supporting_information for A new lignan from Schefflera arboricola by Chang-Qing Ye, Jia-Yi Zhang, Zhi-Cheng Ye, Mei-Tian Xiao, Xu-Dong Zhou and Jing Ye in Journal of Chemical Research