An efficient semi-synthesis of 1-hydroxyl oleanolic acid analogs

Article abstract of DOI:10.1080/10286020.2017.1311873

An efficient route for the semi-synthesis of either 1α- or 1β-OH epimers of 1-hydroxy-3-deoxyolean-12-en-28-oic acid (1), 6–8 steps from oleanolic acid is reported. The synthesis involves stereoselective formation of α,β-unsaturated epoxy ketone and subsequent Wharton reaction as key steps, offering a new access to the 1-O-substituted oleanolic acid-type pentacyclic triterpenoids.

Full text of DOI:10.1080/10286020.2017.1311873

Journal of Asian Natural Products Research
ISSN: 1028-6020 (Print) 1477-2213 (Online) Journal homepage: http://www.tandfonline.com/loi/ganp20
An efficient semi-synthesis of 1-hydroxyl oleanolic
acid analogs
Da-Hui Zhang, Wei-Shuo Fang & Shao-Rong Wang
To cite this article: Da-Hui Zhang, Wei-Shuo Fang & Shao-Rong Wang (2017): An efficient semi-
synthesis of 1-hydroxyl oleanolic acid analogs, Journal of Asian Natural Products Research, DOI:
10.1080/10286020.2017.1311873
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Date: 10 April 2017, At: 02:07

Journal of asian natural Products research, 2017
http://dx.doi.org/10.1080/10286020.2017.1311873
An efficient semi-synthesis of 1-hydroxyl oleanolic acid
analogs
Da-Hui Zhanga, Wei-Shuo Fanga and Shao-Rong Wanga,b
astate Key laboratory of Bioactive substances and functions of natural Medicines, institute of Materia Medica,
b
chinese academy of Medical sciences & Peking union Medical college, Beijing 100050, china; center for
drug evaluation, china food and drug administration, Beijing 100038, china
ABSTRACT
ARTICLE HISTORY
received 23 January 2017
accepted 21 March 2017
An efficient route for the semi-synthesis of either 1α- or 1β-OH
epimers of 1-hydroxy-3-deoxyolean-12-en-28-oic acid (1), 6–8 steps
from oleanolic acid is reported. The synthesis involves stereoselective
formation of α,β-unsaturated epoxy ketone and subsequent Wharton
reaction as key steps, offering a new access to the 1-O-substituted
oleanolic acid-type pentacyclic triterpenoids.
KEYWORDS
oleanolic acid; semi-
synthesis; 1-hydroxy-3-
deoxyolean-12-en-28-oic
acid; Wharton reaction
1. Introduction
In the past decades, many pentacyclic triterpenes with an O-linked substituent at C-1
from natural source were reported. Biological evaluations of these compounds disclosed
their diverse biological activities, such as antibacterial [1–3], antifungal [4], antitumor
[5–12], antiproliferative [13,14], inhibition against α-glucosidase [15], antioxidant [3],
and inhibition of NO production [16]. In some reports, it was indicated that the presence
of C-1 O-substituent, especially 1-OH, may play a critical role for biological properties
[3,4,10,11,14]. To facilitate the systematic understanding of the biological importance of
1-oxygenated triterpenes, the synthesis of 1-OH triterpenes from abundant naturally occur
-
ring 3-OH triterpenes (such as oleanolic acid, ursolic acid, and betulinic acid), instead of
isolation of natural compounds is desired.
Here, we report an efficient access to 1-hydroxy-3-deoxyolean-12-en-28-oic acid (1) from
oleanolic acid (2). To the best of our knowledge, this is the first report on the synthesis of
1, which has not been found in natural resource (Figure 1).
CONTACT shao-rong Wang
wangshaorong@outlook.com, purplewinds@126.com
supplemental data for this article can be accessed at http://dx.doi.org/10.1080/10286020.2017.1311873.
© 2017 informa uK limited, trading as taylor & francis Group

2
D.-H. ZHANG ET AL.
2. Results and discussion
e synthesis of 1 is illustrated in Scheme 1. e 3-OH of 2 was oxidized to ketone by
Jones’ reagent to give 3-oxoolean-12-en-28-oic acid (3) in 92% yield. en, 28-COOH in
3 was protected with benzyl, by reacting with benzyl chloride in the presence of K2CO3
in dioxane, to afford 4 in 86% yield [17]. e introduction of the double bond into ring A
was first attempted by bromination at the α position of the ketone, followed by elimination
of the bromine atom. However, it was unsuccessful. Direct oxidation-elimination with the
mild oxidant 2-iodoxybenzoic acid (IBX) also failed to furnish the desired product [18].
Afer a few experiments, it was found that with PhSeCl/H2O2, compound 5 can be obtained
in good yield [19], but this method is not applicable to large-scale synthesis because of the
use of expensive and high-toxic selenium reagent. Finally, 4 was transformed to trimethyl-
silyl enol ether and then oxidized by 2,3-dichloro-5,6-dicyanobenzoquinone (DDQ) in the
Figure 1. structures of compounds 1 and 2.
Scheme 1. synthesis of compound 1. reagents and conditions: (a) Jones’ reagent, chcl3:acetone (1:1),
r.t., 92%; (b) Bncl, K2co3, dioxane, 85 °c, 86%; (c) i. tMsotf, et3n, ch2cl2, −78 °c; ii. ddQ, Bstfa, toluene,
75 °c, 80% for two steps; (d) h2o2, naoh, thf, 90%; (e) 85% aq. nh2nh2·h2o, acoh, etoh, reflux, 94%; (f)
Pd/c, h2, Meoh, 83%; (g) Jones’ reagent, chcl3:acetone (1:1), r.t., 82%; (h) cecl3·7h2o, naBh4, etoh:thf
(1:1), 0 °c, 42% for 1a, 48% for 1b.

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
3
presence of N,O-bis(trimethylsily) trifluoroacetamide (BSTFA) to afford benzyl 3-oxoolean-
1,12-dien-28-oate (5) with a yield of 80.0% for two steps [20,21]. Next, the double bond of
the α,β-unsaturated ketone was regioselectively epoxidized by H2O2 under basic condition
without affecting another double bond in ring C. Compound 6 was obtained stereospecifi-
cally, and the stereochemistry of epoxide was assigned as α by the comparison of its 1HNMR
coupling constant with that of structurally similar 1α, 2α-epoxy-3-oxo-oleanolic acid deriv-
ative [19]. A reasonable explanation for this specificity is that the reaction occurred at the
less sterically hindered α face of the molecule, and the formation of β epoxide is disfavored
due to very strong 1,3-interaction between the methyl groups at C-24 and C-25. en 6 was
transformed into allylic alcohol 7 by Wharton reaction, by the treatment with 85% hydrazine
hydrate in the presence of excess AcOH [22]. Microwave irradiation (50 W, 110 °C) could
accelerate the reaction significantly. During the hydrogenation of 2, 3-double bond over 10%
Pd/C, 28-benzyl protective group was also removed to furnish 1a in 83.3% yield. e double
bond at C-12 was not affected as well, since the steric hindrance around ring C prevents
the substrate approaching the surface of the catalyst used in the hydrogenation reaction.
e 1HNMR signal for H-1 of 1a appeared as a singlet, proving its equatorial orientation,
consistent with the reported coupling constant of 1α-hydroxy-3-deoxy glycyrrhetinic acid
[23]. Oxidation of 1-OH in 7 furnished the 1-oxo-3-deoxyolean-12-en-28-oic acid (8),
which was reduced by NaBH4 to afford 1a and its isomer 1b in almost equal amount in the
presence of CeCl3·7H2O. In contrast to 1a, the 1HNMR signal for H-1 of 1b appeared as a
double doublet (J = 4.8, 10.8 Hz) indicating its axial orientation.
Although there are some reports with respect to the introduction of a hydroxyl group into
C-1 of other triterpenes by direct allylic oxidation of the 2, 3-dehydro derivatives [24,25],
the yields of these reactions are not satisfactory or the methodology was not applicable to
the substrates bearing two double bonds in both rings A and C because of poor selectivity.
For example, Amer et al. [23] provided an alternative way when exploring the synthesis of
1α-hydroxy-3-deoxy glycyrrhetinic acid, in which a key step of epoxidizing 2, 3-double bond
by m-chloroperbenzoic acid (m-CPBA) was involved. But this method is not applicable to
most oleanane and ursane triterpenes, as the double bond in ring C frequently observed in
these triterpenes could also be oxidized.
In summary, we have completed an efficiently synthetic approach to both 1α- and 1β-OH
epimers of 1 stereoselectively, offering a new access to 1-O-substituted-3-deoxy pentacyclic
triterpenes. Further derivatization and biological evaluation of their analogs are under
investigation in our lab.
3. Experimental
3.1. General experimental procedures
1H and 13C NMR spectra were measured on Varian spectrometers (Varian Corp., CA,
USA). e mass spectra (MS) were measured on Agilent 1100 LC/MSD high performance
ion trap mass spectrometer (Agilent Technologies, Waldbronn, Germany). Oleanolic acid
(purity > 98%) was purchased from the Division of Chinese Materia Medica and Natural
Products, National Institute for the Control of Pharmaceutical and Biological Products
(NICPBP), China Food and Drug Administration, Beijing, China. All other reagents were
purchased from Alfa Aesar, Shanghai, China, and of standard quality and used without

4
D.-H. ZHANG ET AL.
further purification. All solvents were purchased from Beijing Chemical Works, Beijing,
China, and dried before use through standard workflow.
3.2. 3-Oxoolean-12-en-28-oic acid (3)
To a suspension of oleanolic acid (2) (500 mg, 1.1 mmol) in 50 ml of CHCl3/acetone (1:1) was
added a solution of Jones’ reagent (4 ml) dropwise over 30 min at room temperature until
the color of the solution maintained yellow, and the mixture was stirred for an additional
15 min. en MeOH (10 ml) was added, and the resulting mixture was stirred for another
15 min to remove the excess oxidant before it was concentrated in vacuo. e residue was
diluted with CH2Cl2, washed with a saturated solution of NaHCO3, dried over Na2SO4
and concentrated in vacuo. e residue was purified by column chromatography on silica
gel (hexane:acetone = 5:1) to afford 3 (460 mg, 92%) as a white solid. 1HNMR (300 MHz,
CDCl3): δ 5.30 (1H, t, J = 3.3 Hz, H-12), 2.68 (1H, dd, J = 4.5, 13.8 Hz, H-18), 2.54–2.36
(2H, m, H-2), 2.00–1.81 (m, 4H), 1.81–1.48 (m, 6H), 1.48–1.09 (m, 11H), 1.14 (3H, s, CH3),
1.08 (3H, s, CH3), 1.04 (3H, s, CH3), 1.02 (3H, s, CH3), 0.92 (3H, s, CH3), 0.90 (3H, s, CH3),
0.80 (3H, s, CH3). 13CNMR (75 MHz, CDCl3): δ 217.7, 183.9, 143.6, 122.4, 55.3, 47.4, 46.9,
46.6, 45.8, 41.7, 41.0, 39.2, 39.1, 36.8, 34.1, 33.8, 33.0, 32.4, 32.1, 30.7, 27.7, 26.4, 25.8, 23.5,
23.5, 22.9, 21.4, 19.5, 16.9, 15.0. ESI-MS: m/z 455.4 [M + H]+.
3.3. Benzyl 3-oxoolean-12-en-28-oate (4)
To a solution of compound 3 (20 mg, 0.044 mmol) in dioxane (2 ml) was added K2CO3
(42.8 mg, 0.31 mmol) and benzyl chloride (50 μl, 0.44 mmol). e mixture was refluxed
at 85 °C for 6 h before filtration. e filtrate was concentrated in vacuo. e residue was
purified by column chromatography on silica gel (hexane:acetone = 10:1) to afford product
4 (20.4 mg, 86%) as a white solid. 1HNMR (300 MHz, CDCl3): δ 7.36–7.26 (5H, m, Bn),
5.31 (1H, t, J = 3.6 Hz, H-12), 5.12–5.04 (2H, ABq, J = 12.4 Hz, CH2 of Bn), 2.92 (1H, dd,
J = 6.0, 13.6 Hz, H-18), 2.58–2.32 (2H, m, H-2), 2.05–1.80 (m, 4H), 1.80–1.50 (m, 5H),
1.50–1.10 (m, 11H), 1.13 (3H, s, CH3), 1.08 (3H, s, CH3), 1.04 (3H, s, CH3), 1.01 (3H, s,
CH3), 0.92 (3H, s, CH3), 0.90 (3H, s, CH3), 0.65 (3H, s, CH3). 13CNMR (75 MHz, CDCl3):
δ 217.7, 177.4, 143.8, 136.4, 128.4 (2C), 128.0 (2C), 127.9, 122.3, 65.9, 55.3, 47.4, 46.8, 46.8,
45.8, 41.8, 41.5, 39.3, 39.1, 36.7, 34.1, 33.9, 33.1, 32.3, 32.2, 30.7, 27.6, 26.4, 25.8, 23.6, 23.5,
23.0, 21.5, 19.6, 16.8, 15.0. ESI-MS: m/z 545.3 [M + H]+.
3.4. Benzyl 3-oxoolean-1,12-dien-28-oate (5)
To a solution of compound 4 (94 mg, 0.17 mmol) in dry CH2Cl2 (1 ml) was added Et3N
(0.2 ml, 1.5 mmol) and TMSOTf (0.13 ml, 0.73 mmol) at −78 °C under N2. Afer 1 h, the
reaction mixture was diluted with CH2Cl2 (5 ml) and quenched with cold water (3 ml), then
extracted with CH2Cl2. e organic layer was dried over MgSO4 and concentrated in vacuo.
e crude product was used in the next step without further purification.
e residue mentioned above dissolved in dry toluene (2 ml) was added BSTFA (40 μl,
0.17 mmol) and DDQ (183 mg, 0.85 mmol) at room temperature, and then the mixture was
heated to 75 °C. Afer 2.5 h, the reaction was quenched with a mixture of CH2Cl2 (6 ml) and
aq. NaHSO3 (1%, 2 ml), filtrated, washed with 2 N hydrochloric acid, and dried over Na2SO4

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
5
before it was concentrated in vacuo. e residue was purified by column chromatography
on silica gel (hexane:EtOAc = 20:1) to afford product 5 (74.9 mg, 80%) as a white solid.
1HNMR (300 MHz, CDCl3): δ 7.36–7.30 (5H, m, Bn), 7.02 (1H, d, J = 10.2 Hz, H-1), 5.79
(1H, d, J = 10.5 Hz, H-2), 5.35 (1H, t, J = 3.9 Hz, H-12), 5.13–5.03 (2H, ABq, J = 12.3 Hz,
CH2 of Bn), 2.92 (1H, d, J = 9.0 Hz, H-18), 2.20–1.90 (m, 3H), 1.85–1.41 (m, 10H), 1.44–1.05
(m, 3H), 1.14 (6H, s, CH3), 1.13 (3H, s, CH3), 1.09 (3H, s, CH3), 0.93 (3H, s, CH3), 0.90 (3H,
s, CH3), 0.90–0.80 (m, 2H), 0.67 (3H, s, CH3). 13CNMR (75 MHz, CDCl3): δ 205.3, 177.3,
159.1, 144.2, 136.4, 128.4 (2C), 128.1 (2C), 128.0, 125.0, 121.8, 66.0, 53.4, 46.8, 45.7, 44.5,
42.0, 41.7, 41.6, 40.0, 39.4, 33.8, 33.1, 32.5, 32.3, 30.7, 27.8, 27.6, 25.7, 23.6, 23.3, 23.0, 21.6,
18.9, 18.6, 17.3. ESI-MS: m/z 543.3 [M + H]+.
3.5. Benzyl 1α,2α-epoxy-3-oxoolean-12-en-28-oate (6)
To a solution of compound 5 (72.6 mg, 0.15 mmol) in THF (3.5 ml) was added 2 N aq. NaOH
(0.5 ml) and a MeOH (1 ml) solution of 30% aq. H2O2 (0.5 ml) at 0 °C. e mixture was
stirred at room temperature for 4.5 h and quenched with a mixture of saturated aq. NaHSO3
(5 ml) and aq. NaOH (5%, 5 ml). e organic layer was concentrated in vacuo and the water
layer was acidized with 6 N hydrochloric acid before it was extracted with CH2Cl2, washed
with saturated solution of NaHCO3 and dried over Na2SO4. Afer concentrated in vacuo,
the residue was purified by column chromatography on silica gel (hexane:EtOAc = 1:1) to
1
afford product 6 (67 mg, 90%) as a white solid. HNMR (300 MHz, CDCl3): δ 7.35–7.30
(5H, m, Bn), 5.34 (1H, br s, H-12), 5.12–5.03 (2H, ABq, J = 12.6 Hz, CH2 of Bn), 3.48 (1H, d,
J = 4.5 Hz, H-2), 3.36 (1H, d, J = 4.5 Hz, H-1), 2.93 (1H, d, J = 11.5 Hz, H-18), 2.20–1.80 (m,
5H), 1.80–1.50 (m, 4H), 1.80–1.25 (m, 5H), 1.25–1.10 (m, 2H), 1.19 (3H, s, CH3), 1.10–0.80
(m, 2H), 1.09 (3H, s, CH3), 0.99 (3H, s, CH3), 0.93 (6H, s, CH3), 0.91 (3H, s, CH3), 0.64 (3H, s,
CH3). 13CNMR (75 MHz, CDCl3): δ 211.8, 177.3, 144.2, 136.4, 128.4 (2C), 128.0 (2C), 127.9,
121.7, 65.9, 63.9, 56.9, 46.8, 46.0, 45.7, 44.8, 41.9, 41.6, 40.6, 39.5, 38.5, 33.8, 33.1, 32.3, 32.1,
30.7, 28.0, 27.6, 25.6, 23.8, 23.6, 23.00 20.9, 18.8, 17.2, 14.9. ESI-MS: m/z 559.6 [M + H]+.
3.6. Benzyl 1α-hydroxy-3-deoxyolean-2,12-dien-28-oate (7)
To a solution of compound 6 (5 mg, 0.009 mmol) in EtOH (0.2 ml) was added 85% aq.
NH2NH2·H2O (9.8 μl, 0.27 mmol) at 0 °C. Afer 15 min, a portion of AcOH (92.6 μl,
1.62 mmol) was added, and the reaction mixture was heated to reflux for 6 h and then
quenched by water (1 ml). e water layer was extracted with CH2Cl2, washed with satu-
rated solution of NaHCO3, dried over Na2SO4, and concentrated in vacuo. e residue was
purified by column chromatography on silica gel (hexane:EtOAc = 25:1) to afford product
1
7 (4.6 mg, 94%) as a white solid. HNMR (300 MHz, CDCl3): δ 7.35–7.30 (5H, m, Bn),
5.73 (1H, dd, J = 6.0, 10.2 Hz, H-2), 5.52 (1H, d, J = 9.9 Hz, H-3), 5.32 (1H, t, J = 3.6 Hz,
H-12), 5.13–5.03 (2H, ABq, J = 12.6 Hz, CH2 of Bn), 3.54 (1H, d, J = 5.7 Hz, H-1), 2.92
(1H, d, J = 10.5 Hz, H-18), 2.15–1.80 (m, 3H), 1.80–1.20 (m, 9H), 1.20–1.00 (m, 7H), 1.19
(3H, s, CH3), 0.98 (3H, s, CH3), 0.92 (3H, s, CH3), 0.89 (3H, s, CH3), 0.88 (3H, s, CH3), 0.87
(3H, s, CH3), 0.68 (3H, s, CH3). 13CNMR (75 MHz, CDCl3): δ 177.5, 143.2, 141.6, 136.4,
128.4 (2C), 128.0 (2C), 127.9, 124.0, 122.7, 69.2, 65.9, 46.8, 45.8, 45.0, 42.2, 41.5, 40.3, 39.0,
36.3, 34.8, 33.9, 33.1, 32.4, 31.8, 31.6, 30.7, 27.6, 25.7, 23.6, 23.1 (2C), 22.6, 19.4, 16.9, 15.6.
ESI-MS: m/z 567.3 [M + Na]+.

6
D.-H. ZHANG ET AL.
3.7. 1α-Hydroxy-3-deoxyolean-12-en-28-oic acid (1a)
Compound 7 (20 mg, 0.037 mmol) dissolved in MeOH (1 ml) was hydrogenated over 10%
Pd/C (8 mg) under 1 atm at room temperature for 8 h, and then filtered. e filtrate was
concentrated and the residue was purified by column chromatography on silica gel (hex-
ane:acetone = 8:1) to afford product 1a (14 mg, 83%) as a white solid. 1HNMR (600 MHz,
CDCl3): δ 5.29 (1H, t, J = 3.6 Hz, H-12), 3.50 (1H, s, H-1β), 2.82 (1H, dd, J = 4.2, 13.2 Hz,
H-18), 2.40–1.85 (m, 5H), 1.85–1.00 (m, 16H), 1.18 (3H, s, CH3), 1.00–0.80 (m, 3H), 0.93
(3H, s, CH3), 0.93 (3H, s, CH3), 0.90 (6H, s, CH3), 0.83 (3H, s, CH3), 0.77 (3H, s, CH3).
13CNMR (150 MHz, CDCl3): δ 183.0, 143.7, 122.5, 70.9, 43.4, 46.5, 46.9, 42.0, 41.1, 40.9,
39.2, 38.2, 34.6, 33.8, 33.2, 33.0, 32.9, 32.4, 32.0, 30.7, 27.6, 26.0, 25.4, 23.6, 23.0, 23.0, 21.7,
18.3, 17.3, 16.1. ESI-MS: m/z 479.4 [M + Na]+.
3.8. 1-Oxo-3-deoxyolean-12-en-28-oic acid (8)
To a suspension of compound 1a (15 mg, 0.033 mmol) in 2 ml of CHCl3/acetone (1:1)
was added a solution of Jones’ reagent (25 μl) dropwise over 30 min at room temperature
until the color of the solution maintained yellow, and then the mixture was stirred for an
additional 15 min. MeOH (0.5 ml) was added, and the resulting mixture was stirred for
another 15 min to remove the excess oxidant before it was concentrated in vacuo. e
residue was diluted with CH2Cl2, washed with a saturated solution of NaHCO3, dried over
Na2SO4 and concentrated in vacuo. e residue was purified by column chromatography
on silica gel (hexane:EtOAc = 6:1) to afford product 8 (12.2 mg, 82%) as a white solid.
1HNMR (300 MHz, CDCl3): δ 5.29 (1H, br s, H-12), 2.85–2.05 (m, 5H), 2.05–1.40 (m, 9H),
1.40–0.70 (m, 10H), 1.28 (3H, s, CH3), 1.16 (3H, s, CH3), 1.04 (3H, s, CH3), 0.95 (3H, s,
CH3), 0.93 (3H, s, CH3), 0.91 (3H, s, CH3), 0.81 (3H, s, CH3). 13CNMR (75 MHz, CDCl3):
δ 217.3, 183.9, 142.3, 123.5, 56.3, 51.5, 46.7, 45.5, 41.8, 41.3, 41.2, 39.6, 39.2, 35.5, 33.9,
33.1, 32.9, 32.4, 31.9, 30.6, 29.8, 27.6, 25.7, 25.3, 23.5, 23.1, 22.9, 19.0, 17.8, 15.1. ESI-MS:
m/z 477.4 [M + Na]+.
3.9. 1β-Hydroxy-3-deoxyolean-12-en-28-oic acid (1b)
To a solution of compound 8 (13 mg, 0.029 mmol) in 0.2 ml of EtOH/THF (1:1), CeCl3·7H2O
(16 mg, 0.043 mmol) and NaBH4 (3.3 mg, 0.086 mmol) were added at 0 °C. e mixture
was stirred at room temperature for 3 h, and then quenched with 1 N hydrochloric acid
before it was extracted with CH2Cl2 and washed with saturated aq. NaHCO3. Afer dried
over Na2SO4, the organic layer was concentrated in vacuo and the residue was purified by
column chromatography on silica gel (hexane:EtOAc = 6:1) to afford 1a (5.6 mg, 42%) and
1b (6.1 mg, 48%) as white solids. Compound 1b: 1HNMR (600 MHz, CDCl3): δ 5.28 (1H,
t, J = 3.6 Hz, H-12), 3.32 (1H, dd, J = 4.8, 10.8 Hz, H-1α), 2.80 (1H, dd, J = 4.2, 13.8 Hz,
H-18), 2.40–1.80 (m, 4H), 1.80–1.00 (m, 17H), 1.15 (3H, s, CH3), 1.00–0.80 (m, 3H), 0.97
(3H, s, CH3), 0.93 (3H, s, CH3), 0.91 (3H, s, CH3), 0.85 (3H, s, CH3), 0.80 (3H, s, CH3), 0.77
(3H, s, CH3). 13CNMR (150 MHz, CDCl3): δ 183.1, 142.7, 123.4, 81.7, 54.9, 48.4, 46.5, 45.8,
43.2, 41.4, 40.8, 40.0, 39.9, 33.8, 33.1, 32.9, 32.6, 32.4, 30.7, 29.7, 29.3, 27.7, 27.2, 25.9, 23.6,
22.9, 21.3, 18.7, 17.4, 11.1. ESI-MS: m/z 457.4 [M + H]+.

JOURNAL OF ASIAN NATURAL PRODUCTS RESEARCH
7
Disclosure statement
No potential conflict of interest was reported by the authors.
Funding
is work was financially supported by the National Natural Science Foundation of China [grant
number 81473118] and the Hong Kong, Macao and Taiwan Science & Technology Cooperation
Program of China [grant number 2012DFH30030].
ORCID
Wei-Shuo Fang
http://orcid.org/0000-0002-0972-0640
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