Berberisides A-D: three novel prenylated benzoic acid derivatives and a clerodane glycoside from Berberis tsarica aherndt.

Article abstract of DOI:10.1080/14786419.2020.1839460

Three undescribed prenylated benzoic acid derivatives berberisides A-C (1-3) and a new clerodane glycoside berberiside D (4) were isolated from Berberis tsarica Aherndt. Their structures were elucidated on the basis of extensive NMR and HR-ESI-MS analysis. The in?vitro cytotoxic activities of all isolates were studied against lung carcinoma A549, hepatocellular carcinoma HepG2 and breast carcinoma MDA-MB-231 cell lines. Among them, compounds 1 and 4 exhibited anti-proliferative effects against three tumor cell lines with IC₅₀ ranging from 28.97 ± 2.18 to 35.83 ± 0.72 μM.

Full text of DOI:10.1080/14786419.2020.1839460

Natural Product Research
Formerly Natural Product Letters
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/gnpl20
Berberisides A-D: three novel prenylated benzoic
acid derivatives and a clerodane glycoside from
Berberis tsarica aherndt.
Zhao-Yue Dong , Qing-Hong Zeng , Lin Wei , Xin Guo , Yan Sun , Fan-Cheng
Meng , Guo-Wei Wang , Xiao-Zhong Lan , Zhi-Hua Liao & Min Chen
To cite this article: Zhao-Yue Dong , Qing-Hong Zeng , Lin Wei , Xin Guo , Yan Sun , Fan-Cheng
Meng , Guo-Wei Wang , Xiao-Zhong Lan , Zhi-Hua Liao & Min Chen (2020): Berberisides A-D:
three novel prenylated benzoic acid derivatives and a clerodane glycoside from Berberisꢀtsarica
aherndt., Natural Product Research, DOI: 10.1080/14786419.2020.1839460
To link to this article: https://doi.org/10.1080/14786419.2020.1839460
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NATURAL PRODUCT RESEARCH
https://doi.org/10.1080/14786419.2020.1839460
Berberisides A-D: three novel prenylated benzoic acid
derivatives and a clerodane glycoside from Berberis
tsarica aherndt.
a
a
a
a
a
Zhao-Yue Dong , Qing-Hong Zeng , Lin Wei , Xin Guo , Yan Sun , Fan-Cheng
a
a
b
c
a
Meng , Guo-Wei Wang , Xiao-Zhong Lan , Zhi-Hua Liao and Min Chen
a
b
College of Pharmaceutical Sciences, Southwest University, Chongqing, P.R. China; TAAHC-SWU
Medicinal Plant R&D Center, XiZang Agriculture and Animal Husbandry College, Nyingchi, Tibet, P.R.
c
China; School of Life Sciences, Southwest University, Chongqing, P.R. China
ABSTRACT
ARTICLE HISTORY
Three undescribed prenylated benzoic acid derivatives berberi-
sides A-C (1-3) and a new clerodane glycoside berberiside D (4)
were isolated from Berberis tsarica Aherndt. Their structures were
elucidated on the basis of extensive NMR and HR-ESI-MS analysis.
The in vitro cytotoxic activities of all isolates were studied against
lung carcinoma A549, hepatocellular carcinoma HepG2 and breast
carcinoma MDA-MB-231 cell lines. Among them, compounds 1
and 4 exhibited anti-proliferative effects against three tumor cell
lines with IC50 ranging from 28.97 ± 2.18 to 35.83 ± 0.72 lM.
Received 4 August 2020
Accepted 15 October 2020
KEYWORDS
Berberis tsarica Aherndt.;
Berberisides A-D; diterpene;
prenylated benzoic acids;
cytotoxicity
1. Introduction
Cancer is a major public health problem worldwide. According to statistics, in 2018,
those tumor accounts for the highest mortalities were liver cancer (22.0%) and lung
cancer (10.2%) in males, as well as mammary cancer (15.0%) and lung cancer (13.8%)
in females (Ferlay et al. 2019). Herbs have been identified as a sound source of anti-
cancer agents (Howes 2018). From 1981 to 2019, approximately 65% of all small
CONTACT Min Chen
mminchen@swu.edu.cn
Supplemental data for this article can be accessed online at https://doi.org/10.1080/14786419.2020.1839460.
ß 2020 Informa UK Limited, trading as Taylor & Francis Group

2
Z.-Y. DONG ET AL.
Figure 1. The structure of compounds 1–4.
anticancer drugs that are used clinically are either natural products, analogues or
mimics of the parent natural products, such as paclitaxel, camptothecin and cephalo-
taxine (Newman and Cragg 2020).
Plants of Berberis are widely used for treatment of cancers, dysentery, jaundice and
eczema with a long history (Yao et al. 2016). Among them, Berberidis Radix were
included in Pharmacopoeia of the People’s Republic of China (Chinese Pharmacopoeia
Commission 2020). Previous phytochemistry and pharmacology investigations have
shown that extractions or constituents from Berberis exhibiting various activities, such
as anticancer, antioxidant, antimicrobial, hypoglycemic and hypocholesterolemic activ-
ities (Kong et al. 2009; Zhang et al. 2010; Bahare et al. 2019; Cossiga et al. 2019;
Zhang et al. 2019). Especially, the anti-cancer research of alkaloids from Berberis has
attracted much attention in recent years (Jabbarzadeh Kaboli et al. 2014; Boudjlida
et al. 2019; Koutova et al. 2020).
Berberis tsarica Aherndt., mainly distributed in Tibet of China (Editorial Committee
of flora of China 2001), also used as a folk herbal medicine. However, there has been
no chemical or biological report about it. In order to explore active compounds for
treatment of cancer, the phytochemical investigation on dry branches of B. tsarica led
to isolation of 4 novel compounds (Figure 1) including three bisprenylated benzoic
acids (1-3) and a clerodane glycoside (4) . Their structures were identified by HR-ESI-
MS, NMR, ORD (Optical Rotatory Dispersion) and acid hydrolysis analysis. This paper
deals with the isolation and structural elucidation of new compounds as well as evalu-
ation of their in vitro cytotoxicity.
2
. Results and discussion
.1. Structural elucidation of compounds
Compound 1 was purified as colorless gum. The molecule formula, C H O , was
2
17 22 4
-
established by HR-ESI-MS (m/z 289.1445 [M-H] , calcd. for C H O 289.1440), requiring
17 21 4
seven indices of hydrogen deficiency.
1
The H-NMR spectrum showed two aromatic protons (d : 7.68 (s, H-6), 7.64 (s, H-2),
H
together with an olefinic proton signals at d : 5.31 (t, J ¼ 7.47 Hz, H-9) which was
H
linked with a methylene (3.30, J ¼ 7.43 Hz, H-8), an oxygenated methane signal at d :
H
4
.68 (dd, J ¼ 9.31, 8.26 Hz, H-14). At the same time, another methylene (3.22 (dd,
J ¼ 8.67, 3.70 Hz, H-13) and four methyl groups signals at d : 1.74 (s, H-11), 1.73 (s, H-
H

NATURAL PRODUCT RESEARCH
3
1
1
1
2), 1.25 (s, H-17) and 1.24 (s, H-16) also be observed. The H- H COSY spectrum of
compound 1 indicated the correlations from H-8 (3.30 (d, J ¼ 7.43 Hz)) to H-9 (5.31 (t,
J ¼ 7.47 Hz) and H-14 (4.68 (dd, J ¼ 9.31, 8.26 Hz)) to H-13 (3.22 (dd, J ¼ 8.67, 3.70 Hz)),
revealing the presence of two spin-coupled fragments.
1
3
The C-NMR and HSQC spectra showed nine unsaturated carbons in the low field
(dC 170.8-123.0) including three tertiary carbons and six quaternary carbons, which
indicated that there are an aromatic ring, a carboxyl group and a pair of olefinic car-
13
bons. From d 91.3 to 18.0, the C-NMR spectrum of compound 1 exhibited eight car-
C
bons, attributed a quaternary, a methine, two methylene and four methyl groups.
1
13
Comparison of the H and C-NMR data (Table S1) with known compound revealed
that compound 1 was a derivative of anodendroic acid (Zhao et al. 2017).
From the HMBC date, the proton resonance at H-11 (d : 1.74)/H-12 (d : 1.73) corre-
H
H
lated with the signals at d 134.0 (C-10) and 123.0 (C-9), H-8 correlated with the C-2 (d :
C
C
1
1
1
31.7), C-3 (d : 124.0), C-4 (d : 163.5) and C-9 (d : 123.0). And the H- H COSY spectrum
C C C
showed the cross-peaks from H-9 (d : 5.31 (t, J ¼ 7.47 Hz)) to H-8 (d : 3.30 (d,
H
H
J ¼ 7.43Hz)). The above data were indicative of the presence of an isopentenyl group
which located in C-3. A connection of carboxyl to C-1 (123.0) was determined due to the
correlation between H-2 (7.64)/H-6 (7.68) with C-7 (170.8) in the HMBC spectrum (Figure
S35). Thus, the planar structure was established as anodendroic acid-3-isopentenyl. The
absolute configuration of C-14 was determined by comparison of the optical rotation
(
[a]25 D ¼ þ 79.5 (c 0.20 MeOH)) with (þ)-S-anodendroic acid ([a]25 D ¼ þ 74 (c 0.70
EtOH)) (Prompanya et al. 2016). The compound 1 has the same optical rotation proper-
ties as (þ)-S-anodendroic acid, therefore, C-14 of compound 1 has the same stereoscopic
configurationthe structure as (þ)-S-anodendroic acid. Then compound 1 was unequivo-
cally established as (þ)-S-anodendroic acid-3-isopentenyl, named berberiside A.
Compound 2 was purified as a yellow gum. Its HR-ESI-MS displayed a protonated
þ
molecule at m/z 313.1410 [M þ Na] (calcd. 313.1416), which is consistent with a
molecular formula of C H O with seven degrees of unsaturation.
1
7 22 4
1
The H-NMR spectrum of compound 2 showed signals for two aromatic protons (d :
H
7
.60 (s, H-2), 7.58 (s, H-6)), an olefinic proton (d : 5.28 (t, J ¼ 7.34Hz, H-9), an oxymethy-
H
line proton (d : 3.77 (dd, J ¼ 7.48, 5.37 Hz, H-14)) and two methylene groups (d : 3.26 (d,
H
H
J ¼ 7.34 Hz, H-8), 3.03 (dd, J ¼ 16.61, 5.33 Hz, H-13a), 2.75 (dd, J ¼ 16.50, 7.53 Hz, H-13b)),
together with four methyl groups (d : 1.73 (s, H-11), 1.72 (s, H-12), 1.36 (s, H-17), 1.26 (s,
H
1
1
H-16)). Meanwhile, the H- H COSY spectrum (Figure S35) showed two optional coupling
systems duo to the correlations of H-8/H-9 and H-13/H-14.
13
Based on the detailed analysis of the C-NMR and HSQC data, an aromatic ring (dC:
155.5 (C-4), 130.7 (C-6), 130.4 (C-2), 130.0 (C-3), 123.7 (C-1), 120.4 (C-5)), an carboxyl group
(
d : 172.2) and a pair of olefinic carbons (d : 133.0 (C-10), 123.7 (C-9) were confirmed. At
C
C
the same time, four methyl groups which signals at 26.1 (C-17), 26.0 (C-12), 21.3 (C-16),
13
1
13
1
8.0 (C-11) also be observed from the C-NMR spectrum. Comparison of the H and C-
NMR data (Table S1) further with known compound revealed that compound 2 was a
derivative of 2H-1-benzopyran-6-carboxylic acid, 3,4-dihydro-2, 2-dimethyl-8-(3-methyl-2-
buten-1-yl)- (Kunisuke et al. 1969). However, The chemical shift of C-14 moved from dC:
22.5 to 70.2. And further analysis of HMBC spectrum (Fig. S35) confirmed that C-14 was
derived from methylene to oxymethylene, thus the planar structure was determined. And

4
Z.-Y. DONG ET AL.
the absolute configuration of C-14 was defined as S by comparing the optical rotation
(
[a]25 D ¼ ꢀ22.5 (c 2.0 MeOH)) with (-) methyl-2, 2-dimethyl-3-hydroxychromanyl-6-for-
mate ([a]25 D ¼ ꢀ12 (c 2.5 CHCl ) (Xie et al. 2004) and named berberiside B.
3
Compound 3 was purified as a yellow gum with the molecular formula C H O ,
13 14 4
þ
which was established by the HR-ESI-MS at m/z 233.0828 [M þ Na] (calcd. for
C H NaO 233.0814), requiring seven indices of hydrogen deficiency. The 1D (Table
1
3
14
4
S1) and 2D NMR data of compound 3 closely resembled those of 4-hydroxy-3-prenyl-
benzoic acid (I oꢀ ca et al. 2016) suggested that compound 3 shared the same skeleton
with that of 4-hydroxy-3-prenyl-benzoic acid, except for the presence of an aldehyde
group instead of the proton of C-5 in 4-hydroxy-3-prenyl-benzoic acid. This conclusion
was confirmed by the HMBC correlations (Figure S35) from H-13 (d : 9.96) to C-4 (d :
H
C
1
63.1) C/C-5 (d : 121.1)/C-6 (d : 135.0), thus the structure of compound 3 was identi-
C C
fied as 5-aldehyde-4-hydroxy-3-prenyl-benzoic acid, and was named as berberiside C.
Compound 4 was obtained as colorless gum. Its molecule formula was determined
þ
as C H O by HR-ESI-MS (m/z 491.2981 [M þ Na] , calcd. for C H NaO 491.2979),
2
6
44
7
26 44
7
which indicated five degrees of unsaturation in the structure.
1
The H-NMR spectrum of compound 4 showed two olefinic proton signals at d :
H
5
.75 (1H, t, J ¼ 4.0 Hz, H-3), 5.37 (1H, t, J ¼ 6.8 Hz, H-14), two oxygenated methylenes at
d : 4.41 (1H, d, J ¼ 12.2 Hz, H-18a), 4.17 (1H, d, J ¼ 12.2 Hz, H-18b), 4.09 (2H, d,
H
J ¼ 6.8 Hz, H-15), and four methyl groups at d : 1.7 (3H, s, H-16), 1.16 (3H, s, H-19),
H
0
.84 (3H, s, H-20), 0.81 (3H, d, J ¼ 6.71 Hz, H-17), together with a glucopyranosyl moiety
0
(
5
d : 4.32 (1H, d, J ¼ 7.8 Hz, H-1 ), 3.89 (1H, d, J ¼ 11.7 Hz, H-6’a), 3.69 (1H, dd, J ¼ 12.0,
H
0
0
0
.3 Hz, H-6’b), 3.35 (1H, m, H-5 ), 3.29 (1H, m, H-4 ), 3.27 (1H, m, H-3 ), 3.20 (1H, t,
0
13
J ¼ 8.0 Hz, H-2 ). Based on the detailed analysis of the C-NMR, HSQC and DEPT 135
data, the carbon signals were assigned as four methyl signals at d : 35.0, 18.0, 16.5,
C
1
7
6.3 and two oxygenated methylenes at d : 71.9, 59.5. Six carbon signals (d : 103.9,
C C
8.3, 78.0, 75.3, 71.7, 62.8) were assigned as glucopyranosyl. Besides, two pair of ole-
finic carbons (d : 140.7, 124.4 and 141.0, 127.6) were confirmed via analysis of the
C
1
13
HMBC data combined with HSQC data. By comparison of the H and C-NMR data of
compound 4 with phocantoside B (Li et al. 2017), it was revealed that compound 4
was a clerodane-type diterpene glycoside (Table S1).
The HMBC spectrum (Figure S36) showed the cross-peaks from d : 4.32 to d : 71.9,
H
C
which suggested the glucopyranosyl was linked at C-18. In the NOESY spectrum, the cor-
relations was observed between H-14 with H-12, this suggests that C-12 and H-14 are
located on the same side of the double bond, therefore, The E configuration of
C(13)¼C(14) bond was determined (Figure S36), The correlations between H-8 and 19, H-
1
0 and 19, H-10 and H -11a in the NOESY spectrum indicated that the A/B rings were
2
cis fused in clerodane skeleton. Thus, the relative configuration of compound 4 could be
identified as 5 a, 10 a-cis- or 5 b, 10 b-cis-clerodane. Meanwhile, according to the litera-
ture data, the chemical shifts of methyl protons of CH -20 is affected by its orientation.
3
Usually, for 5 b, 10 b-cis-clerodanes, the chemical shift is about d 0.84, while about 1.08
H
for 5 a, 10 a-cis-clerodanes (Cifuente et al. 2002; Bl €a s et al. 2004; Li et al. 2017). Thus, the
proton chemical shift at d 0.84 of CH -20 in compound 4 suggested that the absolute
H
3
configuration of compound compound 4 was identified as 5 S, 8 R, 9 S, 10 R. The cou-
pling constant value (J1’/2
¼ 7.8 Hz) of the anomeric proton confirmed the b
0

NATURAL PRODUCT RESEARCH
5
configuration of glucopyranosyl (Kumar et al. 2019). Analysis of the acid hydrolysate of
compound 4 and the standard monosaccharides using HPLC method (see in supplemen-
tary material) together with the NMR data proved the existences of a b-D-glucopyrano-
syl. Therefore, the structure of compound 4 was established as (5S, 8 R, 9S, 10 R)-cis-
cleroda-3,13(E)-diene-18-O-b-D-glucopyranoside, which was named as Berberiside D.
2.2. Inhibitory
The cytotoxicity of all isolated compounds 1-4 were evaluated against human lung
cancer (A549), breast cancer (MDA-MB-231) and hepatocellular carcinoma (HepG2) cell
lines using the MTT assay. The results revealed that two compounds (compound 1
and 4) exhibited inhibitory effects against the tested human cancer cell lines (Table
S2). Among them, compound 4 displayed moderate inhibitory effect against MDA-MB-
231, HepG2 and A549 cell lines with IC50 values of 29.13 ± 0.71, 28.97 ± 2.18 and
35.83 ± 0.72 Mm. Compound 1 showed selective inhibitory effect with IC50 values of
30.56 ± 2.01 lM against HepG2 cell.
3. Conclusions
The phytochemical investigations had led to isolation of three undescribed prenylated
benzoic acid derivatives Berbersides A-C (1-3), togerther with one clerodane diterpen-
oid Berberside D (4). To the best of our knowledge, this is the first time that diterpen-
oid has been obtained from Berberis Linn. Meanwhile, compound 1 and 4 exhibited
inhibitory effects on three different cancer cell lines, human lung cancer (A549), breast
cancer (MDA-MB-231) or hepatocellular carcinoma (HepG2) cell lines in vitro.
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
This work was supported by National Natural Science Foundation of China (No. 81774005),
Innovative Research Project for Postgraduate Students of Chongqing (No. CYS19099),
Chongqing Social Undertaking and Livelihood Security Project (No. cstc2017shmsA130079).
References
Bahare S, Zeliha S, Bilge S, Mehtap K, Arun KJ, Nunziatina DT, Chiara S, Luigi M, Jovana R,
Flaviana Mb MB, et al. 2019. Berberis plants-drifting from farm to food applications, phytother-
apy, and phytopharmacology. Foods. 8:522.
Bl €a s B, Zapp J, Becker H. 2004. ent-Clerodane diterpenes and other constituents from the liver-
wort Adelanthus lindenbergianus (Lehm.) Mitt. Phytochemistry. 65(1):127–137.
Boudjlida A, Kaci S, Karaki S, Benayad T, Rocchi p, Smati D, Aouichat SB. 2019. Berberis hispanica
alkaloids extract induced cell death and apoptosis in human laryngeal cancer cells Hep-2. S
Afr J Bot. 125:134–141.

6
Z.-Y. DONG ET AL.
Chinese Pharmacopoeia Commission. 2020. Pharmacopoeia of the People’s Republic of China,
vol.1, China Medical Science Press, Beijing, p. 1p. 4. 15.
Cifuente DA, Borkowski EJ, Sosa ME, Gianello JC, Giordano OS, Tonn CE. 2002. Clerodane diter-
penes from Baccharis sagittalis: insect antifeedant activity. Phytochemistry. 61(8):899–905.
Cossiga V, Lembo V, Guarino M, Tuccillo C, Morando F, Pontillo G, Fiorentino A, Caporaso N,
Morisco F. 2019. Berberis aristata, Elaeis guineensis and Coffea canephora extracts modulate
the insulin receptor expression and improve hepatic steatosis in NAFLD patients: a pilot clin-
ical trial. Nutrients. 11(12):3070.
Editorial Committee of flora of China. 2001. Chinese Academy of Sciences, Flora of China, vol.29,
Science Press, Beijing, p. 80.
Ferlay J, Colombet M, Soerjomataram I, Mathers C, Parkin DM, Pi n~ eros M, Znaor A, Bray F. 2019.
Estimating the global cancer incidence and mortality in 2018: GLOBOCAN sources and meth-
ods. Int J Cancer. 144(8):1941–1953.
Howes MR. 2018. The evolution of anticancer drug discovery from plants. Lancet Oncol. 19(3):
293–294.
Jabbarzadeh Kaboli P, Rahmat A, Ismail P, Ling K-H. 2014. Targets and mechanisms of berberine,
a natural drug with potential to treat cancer with special focus on breast cancer. Eur J
Pharmacol. 740:584–595.
Kong W-J, Zhang H, Song D-Q, Xue R, Zhao W, Wei J, Wang Y-M, Shan N, Zhou Z-X, Yang P,
et al. 2009. Berberine reduces insulin resistance through protein kinase C-dependent up-regu-
lation of insulin receptor expression. Metabolism. 58(1):109–119.
Koutova D, Kulhava M, Havelek R, Majorosova M, Kr ꢀa lovec K, Habartova K, Ho ꢁs t' ꢀa lkov ꢀa A, Opletal
ꢁ
L, Cahlikova L, Rez ꢀa ꢁc ov ꢀa M. 2020. Bersavine: a novel bisbenzylisoquinoline alkaloid with cyto-
toxic, antiproliferative and apoptosis-inducing effects on human leukemic cells. Molecules. 25
(4):964.
Kumar P, Dev K, Sharma K, Sahai M, Maurya R. 2019. New lignan glycosides from Cissus quadran-
gularis stems. Nat Prod Res. 33(2):233–238.
Kunisuke N, Mieko M, Yoshimasa H. 1969. Chemotaxonomical alkaloid studies structures of
Liparis alkaloids. Tetrahedron. 25(13):2723–2741.
Li B, Ali Z, Chan M, Li J, Wang M, Abe N, Wu CR, Khan IA, Wang W, Li SX. 2017. Chemical con-
stituents of Pholidota cantonensis. Phytochemistry. 137:132–138.
I oꢀ ca LP, Rommingera S, Santos MFC, Bandeira KF, Rodrigues FT, Kossuga MH, Nicacio KJ, Ferreira
ELF, Morais-Urano RP, Passos MS. 2016. A strategy for the rapid identification of fungal
metabolities and the discovery of the antivieal activity of pyrenocine A and harzianoptridone.
Quim Nova. 39(6):720–731.
Newman DJ, Cragg GM. 2020. Natural products as sources of new drugs over the nearly four
decades from 01/1981 to 09/2019. J Nat Prod. 83(3):770–803.
Prompanya C, Dethoup T, Gales L, Lee M, Pereira JAC, Silva AMS, Pinto MMM, Kijjoa A. 2016.
New polyketides and new benzoic acid derivatives from the marine sponge-associated fungus
Neosartorya quadricincta KUFA 0081. Mar Drugs. 14(7):134.
Xie ZX, Hu Y, Li Y. 2004. First asymmetric synthesis of (-) methyl 2, 2-dimethyl-3-hydroxychro-
manyl-6-formate. J Chin Phar Sci. 13(2):115–118.
Yao X, Xiao W, Meng YF, Xiao PG. 2016. Perspective on resource utilizaton of the Berberis fruits.
Mod Chin Med. 18(11):1506–1512.
Zhang H, Wei J, Xue R, Wu J-D, Zhao W, Wang Z-Z, Wang S-K, Zhou Z-X, Song D-Q, Wang Y-M,
et al. 2010. Berberine lowers blood glucose in type 2 diabetes mellitus patients through
increasing insulin receptor expression. Metabolism. 59(2):285–292.
Zhang YP, Deng YJ, Tang KR, Chen RS, Liang S, Liang YJ, Han L, Jin L, Liang ZE, Chen YN, et al.
2019. Berberine ameliorates high-fat diet-induced Non-Alcoholic Fatty Liver Disease in Rats
via Activation of SIRT3/AMPK/ACC Pathway . Curr Med Sci. 39(1):37–43.
Zhao MB, Zhou SX, Zhang QY, Wei WF, Li MH, Xing JY, Jiang Y, Tu PF. 2017. Prenylated benzoic
acid derivatives from the stem of Euodia lepta. Nat Prod Res. 31(13):1589–1593.