Bioorganic & Medicinal Chemistry Letters 28 (2018) 476–481

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Bioorganic & Medicinal Chemistry Letters

journal homepage: www.elsevier.com/locate/bmcl

Chemical constituents from Taraxacum officinale and their a-glucosidase

inhibitory activities
Janggyoo Choi a, Kee Dong Yoon b, Jinwoong Kim a,⇑
a
College of Pharmacy and Research Institute of Pharmaceutical Science, Seoul National University, Seoul 08826, Republic of Korea
b
College of Pharmacy, The Catholic University of Korea, Bucheon 14662, Republic of Korea

a r t i c l e i n f o a b s t r a c t

Article history: Three novel butyrolactones (1–3) and butanoates (4–6), namely taraxiroside A–F, were isolated from
Received 26 October 2017 Taraxacum officinale along with twenty-two known compounds (7–28). Their chemical structures were
Revised 6 December 2017 elucidated by interpretation of spectroscopic data and comparison with those of literatures. All isolates
Accepted 7 December 2017
were evaluated for their a-glucosidase inhibitory activities. Novel compounds 1–6 (IC50 145.3–181.3
Available online 8 December 2017
lM) showed inhibitory activities similar to that of acarbose (IC50 179.9 lM). Compound 7 and 12 were
the most potent inhibitor with IC50 values of 61.2 and 39.8 lM respectively. Compounds 2 and 12 showed
Keywords:
as mixed-type inhibition, whereas compound 7 and acarbose showed competitive inhibition.
Taraxacum officinale
Butyrolactone
Ó 2017 Elsevier Ltd. All rights reserved.
Butanoate
a-Glucosidase inhibitor
Mixed-type inhibition

Diabetes mellitus is one of the most serious health problems; it
is a chronic metabolic disease resulting in hyperglycemia due to
imbalanced glucose metabolism.1 It is typically classified into
two subtypes; type 1 diabetes mellitus is identified by an acute
deficiency of insulin secretion, whereas type 2 diabetes mellitus
is characterized by hyperglycemia induced by insulin-resistance
that can eventually cause multiple organ damage and various
cardiovascular diseases.2 Type 2 diabetes mellitus accounts for
approximately 90–95% of diabetes cases worldwide. Although
there are several treatment approaches, it is challenging to achieve
optimum glycemic control without adverse effects.3 Therefore,
research is going to find novel antidiabetic. a-Glucosidase inhibitor
suppresses the activity of carbohydrates digesting enzyme to
decrease the absorption of glucose in intestine. Acarbose and
voglibose are clinically used a-glucosidase inhibitors; however,
they cause several gastrointestinal side effects such as flatulence
and diarrhea.4
Taraxacum officinale F.H. Wigg (Compositae) is abundant in the
warm temperate regions of the northern Hemisphere.5 This herba-
ceous plant is traditionally used to treat hepatic disease, diabetes
mellitus, rheumatoid arthritis, cancer and jaundice.6 It exerts
anti-hyperglycemic,7 anti-oxidants,8 anti-inflammatory,9 anti-
allergic and anti-coagulant10 activities. Phytosterols, sesquiterpene
lactones, flavonoids and phenolic acids of T. officinale are
⇑ Corresponding author.
E-mail address: jwkim@snu.ac.kr (J. Kim).
responsible for antidiabetic actions.11 Thus, the aim of this study
was to indentify and isolate novel potent a-glucosidase inhibitors
from T. officinale.12 We isolated six novel compounds (1–6) (Fig. 1)
along with twenty-two known compounds (7–28),13,14 and evalu-
ated them for their a-glucosidase inhibitory activities.
Compound 1 was isolated as a colorless gum, and its molecular
formula was determined to be C26H28O12 by HRESIMS at m/z
555.1465 [M+Na]+ (calcd. for C26H28O12Na, 555.1478). The 1H
NMR spectrum of 1 exhibited signals assignable to two 1, 4-substi-
tuted benzene rings [dH 6.98 (2H, d, J = 8.5 Hz), 6.91 (2H, d, J = 8.5
Hz), 6.69 (2H, d, J = 8.5 Hz) and 6.68 (2H, d, J = 8.5 Hz)], an anome-
ric proton [dH 4.75 (1H, d, J = 8.1 Hz)], a methylene group [dH 2.80
(1H, dd, J = 17.8, 5.9 Hz) and 2.18 (1H, d, J = 17.7 Hz)], two
oxygenated methylene protons [dH 4.34 (2H, m), 3.68 (1H, dd,
J = 11.1, 5.4 Hz), and 3.49 (1H, m)], two carbonyl methylene pro-
tons (dH 3.38 (2H, m) and 3.26 (2H, m) and five oxygenated
methine protons [dH 4.99 (1H, t, J = 9.6 Hz), 4.61 (1H, dd, J = 9.8,
8.1 Hz), 4.53 (1H, dd, J = 6.1, 4.6 Hz), 3.40 (1H, m) and 3.37 (1H,
m)]. The 13C NMR spectrum of 1 indicated the presence of 26 car-
bons, and HSQC, 1H–1H COSY correlations (H-3/H-4, H-4/H-5) and
the HMBC correlations (H-4/C-2, H-5/C-2, H-70 0 /C-200 and C-800 and
H-7000 /C-200 0 and C-8000 ) confirmed the presence of two 4-hydrox-
yphenylacetyl groups and a c-butyrolactone group (Fig. 2). The
13
C NMR signals at dC 98.7, 76.6, 74.9, 71.2, 67.6 and 60.2, as well
as coupling constant of an anomeric proton (J = 8.1 Hz) and LC
analysis15 indicated a b-D-glucose moiety. The connectivity
between the assigned functional groups and the glucose moiety

https://doi.org/10.1016/j.bmcl.2017.12.014
0960-894X/Ó 2017 Elsevier Ltd. All rights reserved.
 J. Choi et al. / Bioorganic & Medicinal Chemistry Letters 28 (2018) 476–481 477

form according to calculated DdSR H values (Fig. 3). According to full

Fig. 1. Chemical structures of compounds 1–6.
was established by HMBC cross peaks of H-10 /C-4, H-20 /C-800 and H-
30 /C-8000 . The absolute configuration of butyrolactone was deter-
mined by Mosher’s method.16 Hydrolysis of compound 1 by b-glu-
cosidase yielded the partial structure of butyrolactone, which was
then treated with (R) and (S)-MTPA-Cl to afford (S)- and (R)-MTPA
esters (1a and 1b, respectively).17,18 The C-4 of 1 was identified as R
analysis of spectroscopic data, compound 1 was identified as 4R-O-
[2,3-di-O-(4-hydroxyphenylacetyl)-b-D-glucopyranosyl]-c-butyro-
lactone, namely taraxiroside A.19
Taraxiroside B (2) was obtained as a colorless gum, and its
molecular formula (C26H28O11) was determined by HRESIMS at
m/z 561.1602 [M+HCOO] (calcd. for C27H29O13, 561.1608). Com-
pound 2 showed 1H and 13C NMR resonances similar to those of
compound 1; however the 4-hydroxyphenylacetyl group was
replaced with a phenylacetyl group. Proton signals observed at
dH 7.30 (2H, t, J = 7.1 Hz), 7.22 (2H, d, J = 6.8 Hz), 7.26 (1H, d, J =
7.2 Hz) and 3.25 (2H, d, J = 5.1 Hz) were assigned to a phenyl group,
and HMBC correlation between H-30 (dH 5.11) and C-8000 (dC 172.9)
indicated that the phenylacetyl group was connected to the C-30
position of a glucopyranosyl moiety (Fig. 2). Based on Mosher’s
rule, the C-4 was determined as R configuration (Fig. 3). Therefore,
the chemical structure of 2 was determined to be 4R-O-[2-O-(4-
hydroxyphenylacetyl)-3-O-(phenylacetyl)-b-D-glucopyranosyl]-c-
butyrolactone.20
Taraxiroside C (3) was obtained as colorless gum and the molec-
ular formula was identified as C18H22O10 by positive mode HRE-
SIMS at m/z 421.1125 [M+Na]+ (calcd. for C18H22O10Na,
421.1111). The 1H and 13C NMR spectra were similar to those of
compound 1, except for the absence of the 4-hydroxyphenylacetyl
group at the C-30 position of the glucose moiety. The C-4 was

Fig. 2. 1H–1H COSY and HMBC correlation of 1–6.

Fig. 3. DdSR
H values for the MTPA esters of 1–6.
478 J. Choi et al. / Bioorganic & Medicinal Chemistry Letters 28 (2018) 476–481

determined to be R configuration, based on Mosher’s method
(Fig. 3). Consequently, compound 3 was elucidated as 4R-O-[2-O-
(4-hydroxyphenylacetyl)-b-D-glucopyranosyl]-c-butyrolactone.21
The molecular formula of taraxiroside D (4) was determined to
be C27H30O13 negative ion peak at m/z 561.1598 [MH] (calcd. for
C27H29O13, 561.1608) from HRESIMS. The exhaustive interpretation
of 1D and 2D NMR spectra revealed the presence of four partial
groups, including glucose, methylbutanoate, 4-hydroxyphenylgly-
oxyl and phenylacetyl groups (Fig. 1; Tables 1 and 2). A b-glucose
moiety was confirmed by six signals at dC 101.7, 78.0, 76.7, 74.5,
69.8 and 62.1, as well as J value of an anomeric proton
(J = 8.0 Hz). The methylbutanoate, 4-hydroxyphenylglyoxyl and

Table 1
1
H NMR (500 MHz) data of 1–6.

No. 1a 2b 3b No. 4b 5b 6b
3 2.80 (1H, dd, 17.8, 5.9), 2.68 (1H, dd, 18.0, 6.2) 2.65 (1H, dd, 18.0, 6.) 2 2.60 (1H, dd, 16.6, 4.6) 2.50 (1H, dd, 16.2, 4.8) 2.48 (1H, dd, 16.3, 5.0)
2.18 (1H, d, 17.7) 2.17 (1H, d, 18.0) 2.13 (1H, d, 18.0) 2.55 (1H, dd, 16.6, 8.1) 2.36 (1H, dd, 16.2, 8.3) 2.32 (1H, dd, 16.2, 8.1)
4 4.53 (1H, t, 6.1) 4.53 (2H, t, 6.1) 4.50 (2H, t, 6.0) 3 4.16 (1H, dd, 8.1, 4.6) 4.07 (1H, dd, 8.3, 4.8) 4.04 (1H, dd, 8.1, 4.8)
5 4.36 (1H, dd, 10.4, 4.3) 4.41 (1H, t, 9.4) 4.41 (1H, t, 10.0) 4 3.65 (2H, d, 4.8) 3.58 (2H, d, 4.8) 3.57 (2H, d, 4.8)
4.33 (1H, t, 9.6) 4.37 (1H, dd, 10.4, 4.3) 4.37 (1H, dd, 10.4, 4.2)
OMe 3.42 (3H, s) 3.67 (3H, s) 3.67 (3H, s)
10 4.75 (1H, d, 8.1) 4.64 (1H, d, 8.0) 4.52 (1H, d, 8.2) 10 4.87 (1H, d, 8.0) 4.69 (1H, d, 8.0) 4.57 (1H, d, 8.0)
20 4.61 (1H, dd, 9.8, 8.1) 4.77 (1H, dd, 9.8, 8.1) 4.69 (1H, t, 8.6) 20 5.02 (1H, dd, 9.8, 8.0) 4.75 (1H, dd, 9.7, 8.0) 4.68 (1H, t, 9.0)
30 4.99 (1H, t, 9.6) 5.11 (1H, t, 9.5) 3.54 (1H, t, 9.2) 30 5.24 (1H, dd, 9.4, 9.6) 5.09 (1H, t, 9.5) 3.52 (1H, t, 9.0)
40 3.40 (1H, m) 3.57 (1H, m) 4.35 (1H, t, 9.2) 40 3.66 (1H, m) 3.56 (1H, m) 3.37 (1H, t, 9.0)
50 3.37 (1H, m) 3.41 (1H, ddd, 9.8, 5.5, 2.2) 3.31 (1H, m) 50 4.16 (1H, dd, 8.1, 4.8) 3.42 (1H, m) 4.16 (1H, m)
60 3.68 (1H, dd, 11.1, 5.4) 3.86 (1H, dd, 12.1, 2.2) 3.87 (1H, d, 12.1) 60 3.90 (1H, dd, 12.0, 2.2) 3.83 (1H, dd, 12.0, 2.3) 3.87 (1H, d, 12.0)
3.49 (1H, m) 3.69 (1H, dd, 12.1, 5.5) 3.67 (1H, dd, 12.1, 5.4) 3.74 (1H, dd, 12.1, 5.2) 3.70 (1H, dd, 11.0, 4.1) 3.68 (1H, m)
200 6.98 (2H, d, 8.5) 6.97 (2H, d, 8.6) 7.11 (2H, d, 8.2) 200 7.77 (2H, d, 8.8) 6.99 (2H, d, 8.8) 7.12 (2H, d, 8.3)
300 6.69 (2H, d, 8.5) 6.72 (2H, d, 8.6) 6.75 (2H, d, 8.2) 300 6.85 (2H, d, 8.8) 6.70 (2H, d, 8.8) 6.72 (2H, d, 8.3)
500 6.69 (2H, d, 8.5) 6.72 (2H, d, 8.6) 6.75 (2H, d, 8.2) 500 6.85 (2H, d, 8.8) 6.70 (2H, d, 8.8) 6.72 (2H, d, 8.3)
600 6.98 (2H, d, 8.5) 6.97 (2H, d, 8.6) 7.11 (2H, d, 8.2) 600 7.77 (2H, d, 8.8) 6.99 (2H, d, 8.8) 7.12 (2H, d, 8.3)
700 3.38 (2H, m) 3.55 (2H, d, 15.5) 3.57 (2H, d, 9.7) 700 3.59 (1H, d, 4.9) 3.60 (2H, s)
3.32 (1H, m)
20 00 6.91 (2H, d, 8.5) 7.22 (2H, d, 6.8) 20 00 7.24 (2H, m) 7.18 (2H, d, 8.3)
30 00 6.68 (2H, d, 8.5) 7.30 (2H, t, 7.1) 30 00 7.22 (2H, m) 7.28 (2H, t, 6.3)
40 00 7.26 (1H, d, 7.2) 40 00 7.17 (1H, t, 7.6) 7.24 (1H, d, 7.2)
50 00 6.68 (2H, d, 8.5) 7.30 (2H, t, 7.1) 50 00 7.22 (2H, m) 7.28 (2H, t, 6.3)
60 00 6.91 (2H, d, 8.5) 7.22 (2H, d, 6.8) 60 00 7.24 (2H, m) 7.18 (2H, d, 8.3)
70 00 3.26 (2H, m) 3.25 (2H, d, 5.1) 70 00 3.71 (2H, s) 3.52 (1H, d, 14.8)
3.43 (1H, m)
a
Data were obtained in DMSO-d6.
b
Data were obtained in MeOH-d4.

Table 2
13
C NMR (125 MHz) data of 1–6.

No. 1a 2b 3b No. 4b 5b 6b
1 1 173.2 173.2 173.3
2 175.5 178.1 178.2 2 37.6 37.7 37.7
3 34.9 36.1 36.1 3 79.1 79.7 79.5
4 74.8 76.6 76.5 4 65.4 65.2 65.2
5 73.7 75.8 75.9 OMe 52.2 52.3 52.4
10 98.7 101.2 101.6 10 101.7 102.1 102.4
20 71.2 73.1 75.2 20 74.5 73.3 75.5
30 74.9 76.8 76.0 30 76.7 77.0 76.1
40 67.6 69.5 71.5 40 69.8 69.6 71.6
50 76.6 78.1 78.3 50 78.0 77.8 78
60 60.2 62.2 62.6 60 62.1 62.2 62.5
100 123.8 126.0 126.4 100 125.1 126.0 126.4
200 130.1 131.6 131.6 200 134.1 131.7 131.7
300 115.0 116.5 116.4 300 117.1 116.4 116.3
400 156.2 157.8 157.7 400 166.1 157.8 157.6
500 115.0 116.5 41.4 500 117.1 116.4 116.3
600 130.1 131.6 173.1 600 134.1 131.7 131.7
700 39.1 41.1 178.2 700 185.4 41.0 41.1
800 170.1 172.4 36.1 800 164.7 172.7 173.3
10 00 124.2 135.5 10 00 135.2 135.4
20 00 130.2 130.6 20 00 130.7 130.6
30 00 115.3 129.7 30 00 129.6 129.6
40 00 156.1 128.2 40 00 128.1 128.1
50 00 115.3 129.7 50 00 129.6 129.6
60 00 130.2 130.6 60 00 130.7 130.6
70 00 39.4 42.0 70 00 41.9 41.8
80 00 170.1 172.9 80 00 172.9 172.9
a
Data were obtained in DMSO-d6.
b
Data were obtained in MeOH-d4.
 J. Choi et al. / Bioorganic & Medicinal Chemistry Letters 28 (2018) 476–481
phenylacetyl groups were determined by HSQC, 1H–1H COSY (H-2/
H-3 and H-3/H-4) and HMBC (-OCH3/C-1, H-2/C-1, H-2 /C-7 and
H-2000 /C-7000 ) cross peaks. The HMBC correlations at H-10 /C-3,
H-20 /C-80 0 and H-30 /C-8000 verified the connectivity between these
partial structures. (Fig. 2) Acid hydrolysis of 4 yielded the butano-
ate structure, the addition of Mosher’s reagents afforded the (S)-
and (R)-MTPA esters (4a and 4b, respectively).22,23 Mosher’s
method revealed that the C-3 position of 4 was in the R configura-
tion (Fig. 3). Thus, compound 4 was elucidated to be methyl-3R-O-
[2-O-(4-hydroxyphenylglyoxyl)-3-O-(phenylacetyl)-b-D-glucopy-
ranosyl]-butanoate.
Compound 5 was isolated as a colorless gum with a molecular
formula of C27H32O12, as deduced by HRESIMS at m/z 593.1863
[M+HCOO] (calcd. for C28H33O14, 593.1870). The 1H and 13C
NMR spectra of 5 were similar to those of compound 4; however
Table 3
a-Glucosidase inhibitory activities of compounds 1–12.
Sample Inhibition rate (%)a
1 58.3 ± 4.6
2 58.9 ± 2.9
3 57.6 ± 2.9
4 56.6 ± 1.6
5 59.7 ± 4.0
6 56.6 ± 1.6
7 77.6 ± 2.9
8 56.9 ± 2.3
9 57.4 ± 2.2
10 1.6 ± 1.4
11 59.1 ± 1.2
12 99.6 ± 6.6
Acarboseb 51.8 ± 3.8
a
Inhibition rate measured at 200 lM. Data expressed as mean ± SD of triplicate
experiments.
b
Positive control.
c
Not determined.
Fig. 4. Lineweaver-Burk plot of a-glucosidase by (a) compound 2, (b) compound 7, (c) compound 12 and (d) acarbose (positive control). [a: 290 lM;
no inhibitor; b: 120 lM; 60 lM; 30 lM; no inhibitor; c: 78 lM;
479
the absence of a carbonyl resonance at C-700 indicated that 5 has
00 00 a 4-hydroxylphenylacetyl moiety, instead of a 4-hydroxylphenyl-
glyoxyl group. HMBC correlations from H-200 (dH 6.99) to C-700
(dC 41.0) indicated that the 4-hydroxyphenylacetyl unit is con-
nected to C-200 (Fig. 2). The C-3 position was deduced to be R con-
figuration by Mosher’s method (Fig. 3). As a result, compound 5
was determined to be methyl-3R-O-[2-O-(4-hydroxypheny-
lacetyl)-3-O-(phenylacetyl)-b-D-glucopyranosyl]-butanoate,
namely taraxiroside E.24
Taraxiroside F (6) was obtained as colorless gum with a molec-
ular formula of C19H26O11 deduced by HRESIMS. The 1H and 13C
NMR spectra showed that its structure was close to that of com-
pound 4; however the phenylacetyl group at the C-30 position
was absent. Correlations at H-3/C-10 and H-20 /C-800 indicated that
a butanoate group was connected to the phenylacetyl group
(Fig. 2). Mosher’s rule confirmed that C-3 has an R configuration
(Fig. 3). Thus, compound 6 was identified as methyl-3R-O-[2-O-
(4-hydroxyphenylacetyl)-b-glucopyranosyl]-butanoate.25
The twenty-two known compounds were identified as 1,2,5-tri-
IC50 (lM) O-p-hydroxyphenylacetyl-L-chiro-inositol (7)26, chrysoeriol (8)27,
151.9 ± 0.6 5,7,30 -hydroxy-40 ,50 -dimethoxy flavone (9)28, methyl 3,4-dihydrox-
145.3 ± 3.6 ycinnamate (10)29, 5,7,40 -hydroxy-30 ,50 -dimethoxy flavone (11)30,
181.3 ± 4.3 luteolin (12)31, 3-glycerindole (13)32, calquiquelignan D (14),
165.1 ± 4.5
calquiquelignan E (15)33, tricin 40 -O-[threo-b-guaiacyl-(700 -O-
149.9 ± 0.6
165.1 ± 0.6 methyl)-glyceryl] ether (16), tricin 40 -O-[erythro-b-guaiacyl-(700 -
61.2 ± 3.5 O-methyl)-glyceryl] ether (17)34, loliolide (18)35, epiloliolide
155.9 ± 3.2 (19)36, annuionone D (20)37, 11b,13-dihydrotaraxinic acid b-O-glu-
154.1 ± 2.5 copyranoside (21)38, 3,4-dihydroxy-5,7-megastigmadien-9-one
NDc
161.6 ± 2.2
(22)39, komaroveside A (23)40, 6S,9R-roseoside (24), 6S,9S-roseo-
39.8 ± 4.2 side (25)41, adenosine (26)42, aesculetin-7-O-b-D-glucopyranoside
179.9 ± 2.9 (27)43 and syringin (28)44, by the comparison with their spectro-
scopic data and those of literatures.
Compounds 1–28 were evaluated for their a-glucosidase inhibi-
tory effect (Table 3 and Supplementary Table S1).3,45 Novel com-
pounds 1–6 showed a-glucosidase inhibition rates (56.6–61.1%)
145 lM; 72.5 lM;
39 lM; 18 lM; no inhibitor; d: 360 lM; 180 lM; 90 lM; no inhibitor].
480 J. Choi et al. / Bioorganic & Medicinal Chemistry Letters 28 (2018) 476–481
and IC50 values (145.3–181.3 lM) similar to those of acarbose, the
positive control (51.8% and 179.9 M, respectively). Compounds 7
and 12 showed the most potent inhibitory activities against a-glu-
cosidase (77.6 and 99.6%, respectively) at a concentration of 200
lM. Flavonoids with simple functional groups (8, 9 and 11) exhib-
ited inhibitory activities (56.9, 57.4 and 59.1%, respectively) similar
to that of acarbose. The side effects due to the a-glucosidase inhi-
bitor, such as flatulence and diarrhea, were induced by undigested
poly- and oligosaccharides in the colon, leading to bacterial
fermentation.46–48 Acarbose, a complex oligosaccharide, led to
increased side effects as polysaccharides entered the colon com-
pared to voglibose possessing monosaccharide–mimicking struc-
ture (Supplementary Fig. S7).49–51 For this reason, compounds
1–7 could be expected to have fewer side effects than those due
to acarbose, as they have a monosaccharide-based structure.
The type of inhibition exhibited by compounds 2, 7 and 12 were
determined using Lineweaver-Burk plots (Fig. 4).52 Because no
intersection on the Y axis, compound 2 and 12 were identified to
exhibit a mixed-type inhibition. Compound 7 competitively inhib-
ited a-glucosidase similar to acarbose which displayed inhibition
consistent with previous reports.53,54
In summary, twenty-eight compounds were isolated from
T. officinale, including three novel acylated c-butyrolactone glyco-
sides (1–3) and three new acylated butanoate glycosides (4–6).
All compounds were evaluated for their inhibitory effects against
a-glucosidase; compounds 7 and 12 displayed outstanding inhibi-
tory activities (IC50 61.2 and 39.8 lM respectively). The novel
isolates showed activities (IC50 145.3–181.3 lM) similar to acar-
bose (IC50 179.9 lM) and displayed mixed-type inhibition as
observed from their Lineweaver-Burk plots.
Acknowledgement
This work was supported by a grant from National Foundation
of Korea (Grant No. NRF-2017R1A2B4003888).
Conflicts of interest
None.
A. Supplementary data
Supplementary data associated with this article can be found, in
the online version, at https://doi.org/10.1016/j.bmcl.2017.12.014.
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fractionated dandelion (Taraxacum officinale) flower extracts in Vitro. J Agric
Food Chem. 2003;51:301–310.
9. Chen HJ, Inbaraj BS, Chen BH. Determination of phenolic acids and flavonoids in
Taraxacum formosanum Kitam by liquid chromatography-tandem mass
spectrometry coupled with a post-column derivatization technique. Int J Mol
Sci. 2012;13:260–285.
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(Taraxacum officinale) in type 2 diabetes. Rev Diabet Stud. 2016;13:113–131.
12. The whole plant of Taraxacum officinale DAHLST was purchased from
Humanherb Co., Ltd. (Kyungsan, South Korea) and was identified by one of
the author (J.K.). A voucher specimen was deposited in Catholic university of
Korea (# CU201508T/O).
13. General Experimental Procedures: Optical rotations were obtained on a P-2000
digital polarimeter (Jasco, Tokyo, Japan). 1D and 2D NMR spectra (1H and 13C
NMR, 1H–1H COSY, HSQC, and HMBC) were performed using an AscendTM 800
and 500 spectrometer (Bruker, Germany). Mass spectra were recorded on a
6530 ESI-Q-TOF mass spectrometer (Agilent Technologies, Santa Clara, CA,
USA). UV spectra were collected using a UV-1800 spectrometer (Shimadzu,
Japan). Compound isolation was performed on an Agilent 1260 infinity HPLC
system (Agilent Technologies, Santa Clara, CA, USA) equipped with an Inno C18
column (5 lm, 20.0 mm  250 mm, Young Jin Biochrom Co. Ltd., Korea) at a
flow rate of 4.0 ml/min. All organic solvents used for chromatography were of
analytical grade and were obtained from Dae-Jung Chemicals & Metals Co. Ltd.
(Gyunggido, Korea). HPLC grade solvents, including acetonitrile and methanol,
were purchased from JT baker Scientific Korea (Seoul, Korea) and deionized
water was produced using a Millipore Milli-QÒ water purification system. The
following materials were employed for chromatographic analysis: Silica gel 60
and RP-C18 silica gel (Merck, Kenilworth, NJ, USA); Sephadex LH-20
(Pharmacia Co., Stockholm, Sweden); TLC plates pre-coated with silica gel
and silica gel RP-18 (Merck, Kenilworth, NJ, USA).
14. The whole plant of T. officinale (5.0 kg) was powdered and extracted with
methanol (12 L) using an ultrasonic bath. The resulting extract (952.1 g),
obtained by evaporation of the solvent under reduced pressure, was suspended
in water and partitioned with n-hexane, chloroform, ethyl acetate, and butanol.
The CHCl3 fraction was subjected to column chromatography using HP-20
resin, and was eluted with 90% MeOH to afford two subfractions, namely TC1
and TC2. The TC1 subfraction was subjected to column chromatography on a
silica gel column, eluting with CHCl3-MeOH (40:1 ? 1:1) to give five
subfractions, (TC 1-1 to 1-5). Fraction TC 1-2 was then separated using a
Sephadex LH-20 column chromatography, eluting with MeOH to afford four
fractions (TC 1-2-1 to 1-2-4). Fraction TC 1-2-2 was then separated by silica gel
chromatography, eluting with hexane-EtOAc (2:1 ? 1:3) to give four
subfractions (TC 1-2-2-1 to 1-2-2-4). Subsequently, TC 1-2-2-2 and TC 1-2-2-
3 were purified by HPLC (23–35% aqueous MeCN) to yield compounds 18 (10.0
mg), 19 (2.5 mg), 20 (1.7 mg), and 22 (2.0 mg), while TC 1-2-3 was subjected to
HPLC (60% aqueous MeCN) to give compounds 10 (5.3 mg), 11 (15.0 mg), 13
(3.0 mg), 16 (4.9 mg), and 17 (7.3 mg). Compound 8 (7.0 mg) and 9 (2.0 mg)
were obtained by the HPLC purification of fraction TC 1-2-4 (60% aqueous
MeCN). In addition, TC 1-3 was separated by silica gel column chromatography,
eluting with a hexane-EtOAc-MeOH (10:10:0.5 ? 10:10:1) and CHCl3-MeOH
solvent system (5:1 ? 1:1) to yield five subfractions (TC 1-3-1 to 1-3-5).
Compound 12 (35.0 mg) was obtained by the recrystallization of TC 1-3-2.
Furthermore, TC 1-3-3 was separated on a Sephadex LH-20 column
chromatography, eluting with 100% MeOH to give five subfractions (TC 1-3-
3-1 to 1-3-3-5). Compounds 14 (11.0 mg) and 15 (4.0 mg) were obtained by
HPLC purification of fraction TC 1-3-3-5 (42% aqueous MeCN). TC 1-3-4 was
subjected to repeated column chromatography (RP-silica gel and sephadex LH-
20) followed by further purification by HPLC (35% aqueous MeCN) to yield
compounds 2 (8.0 mg), 4 (2.0 mg), and 5 (2.3 mg). Moreover, TC 1-4 was
purified over RP-silica gel column chromatography, eluting with a gradient of
0–10% aqueous MeOH to give a further four fractions (TC 1-4-1 to 1-4-4).
Finally, compounds 1 (7.0 mg), 7 (2.0 mg), and 21 (2.0 mg) were obtained by
HPLC purification of fraction The butanol fraction was separated over a HP-20
column eluted with MeOH-H2O (1:4 ? 4:1) to yield five subfractions (TB 1–5).
The subfraction TB 2 was subjected to a normal silica gel chromatography
eluting with CHCl3-MeOH (10:1 ? 2:8) to get eight subfractions (TB 2-1 to 2-
8). Compound 3 (10.0 mg), 26 (3.5 mg), 27 (12.0 mg) and 28 (8.0 mg) were
isolated by repeated chromatography from TB 2-3 [RP and HPLC, eluting with
MeOH-H2O (1:9 ? 10:0) and MeCN-H2O (30:70 ? 50:50)]. Fraction TB 3 was
chromatographed on a normal silica gel column eluted with CHCl3-MeOH
(10:1 ? 1:1) to give nine subfraction (TB 3-1 to 3-9). Fraction TB 3-4 was
 J. Choi et al. / Bioorganic & Medicinal Chemistry Letters 28 (2018) 476–481
subjected to RP column with MeOH-H2O (1:9 ? 10:0) to give five subfractions
(TB 3-4-1 to TB 3-4-5). Subfraction TB 3-4-2 was isolated by HPLC eluted with
MeCN-H2O (10:90 ? 50:50) to yield four subfractions (TB 3-4-2-1 to TB 3-4-2-
4). Compound 6 (21.0 mg), 23 (7.0 mg), 24 (7.0 mg) and 25 (5.5 mg) were
obtained by HPLC purification of fraction TB 3-4-2-4 (23% aqueous MeCN).
15. Tanaka T, Nakashima T, Ueda T, Tomii K, Kouno I. Facile discrimination of
aldose enantiomers by reversed-phase HPLC. Chem Pharm Bull.
2007;55:899–901.
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NMR. Chem Rev. 2004;104:17–117.
17. Compounds 1–3 (5.0 mg, 5.0 mg and 5.0 mg, respectively) were dissolved in
H2O (3 ml) and hydrolyzed by b-glucosidase (5 mg/ml) at 37 °C for seven days.
After evaporating the solvent under reduced pressure, the mixture was
dissolved in MeOH (2 ml). The supernatant (after centrifuging at 10,000 rpm)
was subjected to RP-HPLC (10% MeCN) to afford a butyrolactone fraction.
18. The butyrolactone fraction was suspended in anhydrous pyridine (800 ll), (R)-
or (S)-MTPA-Cl (10 ll) and 4-(N,N-dimethylamino) pyridine (DMAP). The
mixture was incubated at room temperature overnight, and dried in nitrogen.
(S)-and (R)-MTPA esters (1a and 1b) were isolated by RP-HPLC (10 ? 80%
MeCN). (S)-MTPA ester (1a): 1H NMR (800 MHz, MeOH-d4) dH 8.07 (2H, d, J =
7.2 Hz), 7.63 (1H, m), 7.28 (1H, m), 6.91 (2H, d, J = 5.9 Hz), 4.53 (1H, m), 4.38
(1H, dd, J = 10.0, 4.2 Hz), 4.18 (1H, d, J = 10.0 Hz), 3.67 (3H, s), 2.78 (1H, dd, J =
17.7, 5.9 Hz) and 2.33 (1H, d, J = 17.7). (R)-MTPA-ester (1b): 1H NMR (800 MHz,
MeOH-d4) dH 8.08 (2H, d, J = 7.5 Hz), 7.65 (1H, m), 7.29 (1H, m), 6.88 (2H, d, J =
7.4 Hz), 4.54 (1H, m), 4.40 (1H, dd, J = 10.0, 4.3 Hz), 4.20 (1H, d, J = 10.0 Hz),
3.67 (3H, s), 2.76 (1H, dd, J = 17.8, 5.9 Hz) and 2.31 (1H, d, J = 17.7 Hz).
19. Taraxiroside A (1): Colorless gum; [a]20 D +52.4 (c 0.70, MeOH); UV (MeOH) kmax
218 (4.06), 278 (3.32); 1H NMR (500 MHz) and 13C NMR (125 MHz) see Tables 1
and 2; HRESIMS m/z 555.1465 [M+Na]+ (calcd. for C26H28O12Na, 555.1478).
20. Taraxiroside B (2): Colorless gum; [a]20 D +49.8 (c 0.23, MeOH); UV (MeOH) kmax
219 (3.98), 268 (3.53); 1H NMR (500 MHz) and 13C NMR (125 MHz) see Tables 1
and 2; HRESIMS m/z 561.1602 [M+HCOO] (calcd. for C27H29O13, 561.1608).
(S)-MTPA ester (2a): 1H NMR (800 MHz, MeOH-d4) dH 8.07 (2H, d, J = 7.2 Hz),
7.64 (1H, m), 7.28 (1H, m), 6.90 (2H, d, J = 5.9 Hz), 4.54 (1H, m), 4.39 (1H, dd, J =
10.0, 4.2 Hz), 4.19 (1H, d, J = 10.0 Hz), 3.67 (3H, s), 2.80 (1H, dd, J = 17.7, 5.9 Hz)
and 2.35 (1H, d, J = 17.7). (R)-MTPA-ester (2b): 1H NMR (800 MHz, MeOH-d4) dH
8.08 (2H, d, J = 7.5 Hz), 7.65 (1H, m), 7.29 (1H, m), 6.88 (2H, s), 4.54 (1H, m),
4.41 (1H, dd, J = 10.0, 4.3 Hz), 4.21 (1H, d, J = 10.0 Hz), 3.67 (3H, s), 2.79 (1H, dd,
J = 17.8, 5.9 Hz) and 2.34 (1H, d, J = 17.7 Hz).
21. Taraxiroside C (3): Colorless gum; [a]20 D +25.3 (c 1.00, MeOH); UV (MeOH) kmax
222 (1.43), 274 (0.79); 1H NMR (500 MHz) and 13C NMR (125 MHz) see Tables 1
and 2; HRESIMS m/z 421.1125 [M+Na]+ (calcd. for C18H22O10Na, 421.1111). (S)-
MTPA ester (3a): 1H NMR (800 MHz, MeOH-d4) dH 8.07 (2H, d, J = 7.2 Hz), 7.64
(1H, m), 7.29 (1H, m), 6.92 (2H, d, J = 5.9 Hz), 4.53 (1H, m), 4.39 (1H, dd, J = 10.0,
4.2 Hz), 4.19 (1H, d, J = 10.0 Hz), 3.67 (3H, s), 2.79 (1H, dd, J = 17.7, 5.9 Hz) and
2.33 (1H, d, J = 17.8). (R)-MTPA-ester (3b): 1H NMR (800 MHz, MeOH-d4) dH
8.08 (2H, d, J = 7.5 Hz), 7.65 (1H, m), 7.29 (1H, m), 6.91 (2H, d, J = 7.4 Hz), 4.54
(1H, m), 4.41 (1H, dd, J = 10.0, 4.2 Hz), 4.21 (1H, d, J = 10.0 Hz), 3.67 (3H, s), 2.77
(1H, dd, J = 17.8, 5.9 Hz) and 2.32 (1H, d, J = 17.8 Hz).
22. Compounds 4–6 (1.0 mg, 1.0 mg and 10 mg, respectively) were hydrolyzed by
1N H2SO4 (2 ml), heated at 90 °C for 4 h and neutralized with aqueous Na2CO3
solution. After filtration, the mixtures were purified by RP-HPLC (10% MeCN) to
afford a butanoate fraction.
23. Taraxiroside D (4): Colorless gum; [a]20 D +26.2 (c 0.20, MeOH); UV (MeOH) kmax
219 (4.05), 267 (3.50); 1H NMR (500 MHz) and 13C NMR (125 MHz) see Tables 1
and 2; HRESIMS m/z 561.1598 [MH] (calcd. for C27H29O13, 561.1608). (S)-
MTPA ester (4a): 1H NMR (800 MHz, MeOH-d4) dH 8.08 (2H, d, J = 7.2 Hz), 7.63
(1H, m), 7.37 (1H, m), 6.95 (2H, d, J = 5.9 Hz), 4.45 (1H, m), 4.34 (1H, dd, J = 10.0,
4.4 Hz), 4.18 (1H, d, J = 10.1 Hz), 3.67 (3H, s), 2.53 (1H, dd, J = 17.1, 5.7 Hz) and
2.16 (1H, d, J = 17.1). (R)-MTPA-ester (4b): 1H NMR (800 MHz, MeOH-d4) dH
8.08 (2H, d, J = 7.2 Hz), 7.62 (1H, m), 7.32 (1H, m), 6.99 (2H, d, J = 5.9 Hz), 4.45
(1H, m), 4.37 (1H, dd, J = 10.0, 4.2 Hz), 4.22 (1H, d, J = 10.0 Hz), 3.67 (3H, s), 2.52
(1H, dd, J = 17.8, 5.9 Hz) and 2.13 (1H, d, J = 17.8 Hz).
24. Taraxiroside E (5): Colorless gum; [a]20 D +33.8 (c 0.80, MeOH); UV (MeOH) kmax
218 (3.99), 265 (3.32); 1H NMR (500 MHz) and 13C NMR (125 MHz) see Tables 1
and 2; HRESIMS m/z 593.1863 [M+HCOO] (calcd. for C28H33O14, 593.1870).
(S)-MTPA ester (5a): 1H NMR (800 MHz, MeOH-d4) dH 8.08 (2H, d, J = 7.2 Hz),
7.65 (1H, m), 7.29 (1H, m), 6.88 (2H, s), 4.44 (1H, m), 4.35 (1H, dd, J = 10.0, 4.4
Hz), 4.20 (1H, d, J = 10.1 Hz), 3.57 (3H, s), 2.55 (1H, dd, J = 17.1, 5.7 Hz) and 2.15
(1H, d, J = 17.1). (R)-MTPA-ester (5b): 1H NMR (800 MHz, MeOH-d4) dH 8.08
(2H, d, J = 7.2 Hz), 7.64 (1H, m), 7.29 (1H, m), 6.88 (2H, s), 4.44 (1H, m), 4.39
(1H, dd, J = 10.0, 4.2 Hz), 4.23 (1H, d, J = 10.0 Hz), 3.71 (3H, s), 2.50 (1H, dd, J =
17.8, 5.9 Hz) and 2.13 (1H, d, J = 17.8 Hz).
25. Taraxiroside F (6):Colorless gum; [a]20 D +32.0 (c 0.50, MeOH); UV (MeOH) kmax
218 (3.99), 265 (3.32); 1H NMR (500 MHz) and 13C NMR (125 MHz) see Tables 1
and 2; HRESIMS m/z 453.1392 [M+Na]+ (calcd. for C19H26O11Na, 453.1373). (S)-
MTPA ester (6a): 1H NMR (800 MHz, MeOH-d4) dH 8.07 (2H, d, J = 7.2 Hz), 7.64
(1H, m), 7.29 (1H, m), 6.82 (2H, s), 4.45 (1H, m), 4.34 (1H, dd, J = 10.0, 4.7 Hz),
4.20 (1H, d, J = 10.0 Hz), 3.54 (3H, s), 2.54 (1H, dd, J = 17.6, 5.0 Hz) and 2.16 (1H,
d, J = 17.5). (R)-MTPA-ester (6b): 1H NMR (800 MHz, MeOH-d4) dH 8.09 (2H, d, J
= 7.2 Hz), 6.98 (2H, d, J = 5.9 Hz), 4.44 (1H, m), 4.38 (1H, dd, J = 10.0, 4.2 Hz),
4.24 (1H, d, J = 10.0 Hz), 3.54 (3H, s), 2.51 (1H, dd, J = 17.2, 5.9 Hz) and 2.13 (1H,
d, J = 17.1 Hz).
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