Journal of Asian Natural Products Research

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Three new areca alkaloids from the nuts of Areca

catechu

Shao-Nan Tang, Jian Zhang, Dong Liu, Zhi-Wen Liu, Xiao-Qi Zhang & Wen-Cai
Ye

To cite this article: Shao-Nan Tang, Jian Zhang, Dong Liu, Zhi-Wen Liu, Xiao-Qi Zhang & Wen-
Cai Ye (2017): Three new areca alkaloids from the nuts of Areca catechu, Journal of Asian Natural
Products Research, DOI: 10.1080/10286020.2017.1307187

To link to this article: http://dx.doi.org/10.1080/10286020.2017.1307187

Published online: 28 Mar 2017.

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Download by: [The UC San Diego Library] Date: 01 April 2017, At: 05:36
Journal of Asian Natural Products Research, 2017
http://dx.doi.org/10.1080/10286020.2017.1307187

Three new areca alkaloids from the nuts of Areca catechu

Shao-Nan Tang, Jian Zhang, Dong Liu, Zhi-Wen Liu, Xiao-Qi Zhang and Wen-Cai Ye
Guangdong Provincial Key Laboratory of Pharmacodynamic Constituents of TCM and New Drugs Research,
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University,
Guangzhou 510632, China

ABSTRACT ARTICLE HISTORY

Three new areca alkaloids arecatemines A-C (1–3), together with Received 13 November 2016
five known ones (4–8), were isolated from the nuts of Areca catechu. Accepted 13 March 2017
The structures of new compounds including absolute configurations KEYWORDS
were elucidated using comprehensive spectroscopic and electronic Areca catechu; Arecaceae;
circular dichroism (ECD). The known compounds were identified by areca alkaloids; structural
comparing with data in the literature. elucidation

1. Introduction
The plant Areca catechu L. is widely distributed and cultivated in southern China [1]. The nut
of this plant is a kind of popular food for chewing, and also has been used as a traditional
medicine for the treatment of parasitic infection and upset stomach in China [2,3]. Previous
phytochemical investigation of this plant has led to the isolation of more than 13 pyridines
alkaloids, which exhibited significant positive activities in the nervous system [4,5]. As a part
of a program to search for structurally unique and biologically interesting natural products
[6–8], three new areca alkaloids, arecatemines A-C (1–3) and five known ones, arecoline (4)
[9], arecaidine (5) [10], guvacine (8) [10], homoarecoline (6) [11], N-ethyl-1,2,5,6-tetrahydro-
1-methyl-3-pyridinecarboxamide (7) [12], were isolated from the nuts of A. catechu (Figure
1). In this paper, we describe the isolation and structure elucidation of these areca alkaloids.

2.  Results and discussion

Arecatemine A (1) was isolated as white amorphous powder. Its molecular formula was
assigned as C14H18N2O on the basis of HR-ESI-MS at m/z 231.1495 [M + H]+, representing

CONTACT  Xiao-Qi Zhang  xqzhang74@hotmail.com; Wen-Cai Ye  chyewc@gmail.com

© 2017 Informa UK Limited, trading as Taylor & Francis Group
2   S.-N. TANG ET AL.

Figure 1. Structures of compounds 1–3.

Table 1. 1H and 13C NMR spectral data of compounds 1–3 (CD3OD, δ in ppm, J in Hz)a.
1 2 3
Position δH δC Mult δH δC Mult δH δC Mult
2 3.15 q (2.5) 54.1 CH2 2.72–2.79 m 55.1 CH2 4.20–4.24 m 65.8 CH2
4.02 d (16.1)
3 – 132.9 C 3.17–3.24 m 44.7 CH – 125.2 C
4 6.61–6.63 m 132.0 CH 5.79–5.83 m 124.6 CH 7.14–7.17 m 137.7 CH
5 2.30–2.34 m 26.6 CH2 5.88–5.92 m 128.6 CH 2.86–2.93 m 24.1 CH2
2.52–2.57 m
6 2.51 t (3.8) 51.7 CH2 3.00 q (2.8) 54.7 CH2 3.42–3.49 m 62.5 CH2
7 2.36 s 45.7 CH3 2.37 s 45.5 CH3 3.29 s 59.2 CH3
8 – 169.0 C – 175.5 C – 166.1 C
10 4.40 s 44.0 CH2 4.38 s 44.0 CH2 3.78 s 52.5 OCH3
11 – 140.0 C – 140.0 C – –
12/16 7.26 d (6.3) 128.4 CH 7.27–7.28 m 128.4 CH – –
13/15 7.28–7.29 m 129.4 CH 7.30–7.34 m 129.5 CH – –
14 7.19–7.22 m 128.1 CH 7.23–7.26 m 128.2 CH – –
a
Recorded at 500 MHz for 1H NMR and 125 MHz for 13C NMR.

six degrees of unsaturation. The IR absorption revealed the presence of amino (3370 cm−1),
acylamide groups (1663 cm−1), and aromatic ring (1621, 1539 cm−1). The 1H NMR spectrum
of 1 showed the signals of a single substituted aromatic ring [δH 7.28 (2H, m, H-13/H-15),
7.26 (2H, d, J = 6.3 Hz, H-12/H-16), 7.21 (1H, m, H-14)], an olefinic proton [δH 6.62 (1H,
m, H-4)], a nitrogen methyl [δH 2.36 (3H, s, H-7)], and four methylenes [δH 4.40 (2H, s,
H-10), 3.15 (2H, q, J = 2.5 Hz, H-2), 2.51 (2H, t, J = 3.8 Hz, H-6), 2.32 (2H, m, H-5)]. The
13
C NMR and DEPT spectra of 1 indicated the presence of one nitrogen methyl (δC 45.7),
four methylenes (δC 54.1, 51.7, 44.0, and 26.6), four methines (δC 132.0, 129.4, 128.4, and
128.1), and three quaternary carbons (δC 169.0, 140.0, and 132.9). The above NMR data
suggested 1 could be an arecoline-type derivative. With the 1D and 2D NMR experiments,
all the 1H and 13C NMR signals of 1 were assigned as shown in Table 1.
The 1H-1H COSY spectrum of 1 revealed the presence of two spin-coupling systems
shown in bold in Figure 2. In the HMBC spectrum, the correlations between H-4 and
C-2/C-6/C-8, as well as between nitrogen methyl (H-7) and C-2/C-6, led to the fragment
A of the structure of 1 (Figure 2). Furthermore, the HMBC correlations between H-10 and
C-12/C-16 led to the fragment B of the structure of 1 (Figure 2). Fragment A was linked
to fragment B by the HMBC correlations of H-10 and C-8. Thus, the structure of 1 was
determined as shown.
Arecatemine B (2) was isolated as yellow oil. Its molecular formula was established
as C14H18N2O by HR-ESI-MS at m/z 231.1493 [M  +  H]+, indicating six degrees of
 JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH   3

Figure 2. 1H-1H COSY and key HMBC correlations of 1 and 2.

Figure 3. Calculated and experimental ECD spectra of 2.

unsaturation. The IR absorption revealed the presence of amino (3372 cm−1), acylamide

groups (1666 cm−1), and aromatic ring (1616, 1538 cm−1). The 1H and 13C NMR spectral
data revealed that 2 possessed 14 carbons, including a monosubstituted aromatic ring [δH
7.32 (2H, m, H-13/H-15), 7.27 (2H, m, H-12/H-16) and 7.25 (1H, m, H-14); δC 129.5, 128.4
and 128.2], a double bond [δH 5.90 (1H, m, H-5) and 5.81 (1H, m, H-4), δC 128.6 and 124.6],
three methylenes [δH 4.38 (2H, s, H-10), 3.00 (2H, q, J = 2.8 Hz, H-6) and 2.76 (2H, m, H-2),
δC 44.0, 55.1 and 54.7], and a nitrogen methyl [δH 2.37 (3H, s, H-7); δC 45.5]. The 1D NMR
data of 2 resembled those of compound 1, except for the absence of a methylene (δC 26.6),
a quaternary carbon (δC 132.9), and the presence of two methine carbons (δC 128.6, 44.7).
The olefinic carbon (δC 128.6) was assigned to C-5 based on the 1H-1H COSY correlations
between δH 5.81 (H-4)–5.90 (H-5)–3.00 (H-6). The signal at δC 44.7 was assigned to C-3
based on the 1H-1H COSY correlations between δH 2.76 (H-2)–3.21 (H-3)–5.81 (H-4).
Furthermore, the experimental electronic circular dichroism (ECD) spectrum of 2 showed
positive Cotton effect at 207 nm (Δε + 13.4), which was similar to that in the quantum
chemical ECD calculation in Gaussian 09 software [13] (Figure 3). Hence, the absolute
configuration of 2 was elucidated as 3S.
Arecatemine C (3) was isolated as yellow oil. The molecular formula C8H13NO3 was
established by the HR-ESI-MS ([M + H]+ at 172.0962, calcd for C8H14NO3, 172.0968), 16
mass higher than those of arecoline (4). Analysis of the NMR data of 3 and comparison with
those of arecoline (4) revealed that 3 was an N-oxide of compound 4, which was supported
4   S.-N. TANG ET AL.

by the characteristic downfield shifts of C-2, 6, and 7 (δC 65.8, 62.5 and 59.2). Therefore,
the structure of 3 was established.

3. Experimental
3.1.  General experimental procedures
Optical rotation was carried out using a Jasco P-1020 digital polarimeter (JASCO, Tokyo,
Japan). UV spectra were obtained on a Jasco V-550 UV/VIS spectrometer (JASCO, Tokyo,
Japan), and IR spectra on a Jasco FT/IR-480 plus infrared spectrometer (JASCO, Tokyo,
Japan) with KBr discs. HR-ESI-MS data were detected on an Agilent 6210 ESI/TOF mass
spectrometer (Agilent, Palo Alto, CA, USA). NMR spectra were recorded on Bruker AV-500
spectrometer (Bruker, Karlsruhe, Germany). Column chromatography (CC) was performed
on silica gel (80–100 and 200–300 mesh; Qingdao Marine Chemical Inc., Qingdao, China),
ODS (YMC, Kyoto, Japan), and Sephadex LH-20 (Pharmacia Biotech AB). Preparative
HPLC was carried out on an Agilent 1260 system (G1311 pump and G1315D photodiode
array detector) with a C18 reversed-phase column (20  ×  250  mm, 5  μm, Shiseido Fine
Chemicals Ltd., Japan).

3.2.  Plant material

The areca nuts were collected from Sanya, Hainan Province, China, in October 2014
and identified by Prof. Guang-Xiong Zhou (Jinan University). A voucher specimen (No.
CP2014101403) was deposited at the herbarium of the College of Pharmacy, Jinan University,
Guangzhou, China.

3.3.  Extraction and isolation

The air-dried and powdered areca nuts (30.0 kg) were extracted at room temperature with
95% EtOH to afford a residue (1.1 kg), which was partitioned with CHCl3 and 0.5% HCl
solution. The acidic aqueous phase was basified with aqueous ammonia to pH 9–10 and
partitioned with CHCl3 to obtain the crude alkaloids (40.6 g). The total alkaloid extract
was subjected to silica gel column chromatography and eluted with CHCl3–CH3OH (100:0
→ 0:100) to afford 14 fractions (Fr. A−N). Fr. C (3.8 g) was chromatographed on Sephadex
LH-20 (CH3OH–CHCl3, 7:3) and HPLC (CH3CN–H2O, 20:80) to afford 3 (6.2  mg, tR
15.2 min), 4 (18.2 mg, tR 11.7 min), and 5 (10.4 mg, tR 8.6 min). Fr. E (2.3 g) was subjected
to ODS CC (CH3OH–H2O, 1:9 → 7:3) and HPLC (CH3CN–H2O, 25:75) to yield 1 (5.7 mg, tR
10.8 min), 2 (4.1 g, tR 16.8 min), and 6 (6.5 mg, tR 20.5 min). Fr. G (1.9 g) was separated by
Sephadex LH-20 (CH3OH–CHCl3, 1:1) and further HPLC to afford 7 (7.2 mg, tR 22.8 min)
and 8 (8.5 mg, tR 25.8 min).

3.3.1.  Arecatemine A (1)

White amorphous powder; UV (CH3OH) λmax (log ε): 208 (4.95) nm; IR (KBr) νmax 3370,
2787, 1663, 1621, 1539, 1131, 711, 616 cm−1; 1H and 13C NMR spectral data, see Table 1;
HR-ESI-MS: m/z 231.1495 [M + H]+ (calcd for C14H19N2O, 231.1492).
 JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH   5

3.3.2.  Arecatemine B (2)

D  + 14.8 (c 0.10, CH3OH); UV (CH3OH) λmax (log ε): 207 (4.74) nm; ECD
Yellow oil; [𝛼]25
(MeOD)Δε207.4 nm + 13.4, Δε223.4 nm + 4.1, Δε248.5 nm −1.1; IR (KBr) νmax 3372, 2790, 1666,
1616, 1538, 1133, 710, 619 cm−1; 1H and 13C NMR spectral data, see Table 1; HR-ESI-MS:
m/z 231.1493 [M + H]+ (calcd for C14H19N2O, 231.1492).

3.3.3.  Arecatemine C (3)

Yellow oil; UV (CH3OH) λmax (log ε): 208 (4.71) nm; IR (KBr) νmax 3417, 2927, 1715, 1444,
1382, 1272, 1115 cm−1; 1H and 13C NMR spectral data, see Table 1; HR-ESI-MS: m/z 172.0962
[M + H]+ (calcd for C8H14NO3, 172.0968).

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

Funding
This research work was supported by the National Natural Science Foundation of China [grant
number 81373935] and [grant number U1401225]; and Science and Technology Planning Project
of Guangdong Province [grant number 2013A022100028] and [grant number 2016B030301004].

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