Maplexins, new α-glucosidase inhibitors from red maple (Acer rubrum) stems

Article abstract of DOI:10.1016/j.bmcl.2011.10.073

Thirteen gallic acid derivatives including five new gallotannins, named maplexins A-E, were isolated from red maple (Acer rubrum) stems. The compounds were identified by spectral analyses. The maplexins varied in number and location of galloyl groups attached to 1,5-anhydro-d-glucitol. The isolates were evaluated for α-glucosidase inhibitory and antioxidant activities. Maplexin E, the first compound identified with three galloyl groups linked to three different positions of 1,5-anhydro-d-glucitol, was 20 fold more potent than the α-glucosidase inhibitory drug, Acarbose (IC₅₀ = 8 vs 160 μM). Structure-activity related studies suggested that both number and position of galloyls attached to 1,5-anhydro-d-glucitol were important for α-glucosidase inhibition.

Full text of DOI:10.1016/j.bmcl.2011.10.073

Bioorganic & Medicinal Chemistry Letters 22 (2012) 597–600
Contents lists available at SciVerse ScienceDirect
Bioorganic & Medicinal Chemistry Letters
journal homepage: www.elsevier.com/locate/bmcl
Maplexins, new
a-glucosidase inhibitors from red maple (Acer rubrum) stems
Chunpeng Wan a,b, , Tao Yuan b, , Liya Li b, Vamsikrishna Kandhi c, Nadja B. Cech c, Mingyong Xie a,
,
⇑
Navindra P. Seeram b,
⇑
a State Key Laboratory of Food Science and Technology, Nanchang University, Nanchang 330047, Jiangxi, China
b Bioactive Botanical Research Laboratory, Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, United States
c Department of Chemistry and Biochemistry, University of North Carolina Greensboro, PO Box 26170, Greensboro, NC 27402, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Thirteen gallic acid derivatives including five new gallotannins, named maplexins A–E, were isolated
Received 6 October 2011
Revised 20 October 2011
Accepted 21 October 2011
Available online 28 October 2011
from red maple (Acer rubrum) stems. The compounds were identified by spectral analyses. The maplexins
varied in number and location of galloyl groups attached to 1,5-anhydro-
evaluated for -glucosidase inhibitory and antioxidant activities. Maplexin E, the first compound identi-
fied with three galloyl groups linked to three different positions of 1,5-anhydro- -glucitol, was 20 fold
more potent than the -glucosidase inhibitory drug, Acarbose (IC50 = 8 vs 160 M). Structure–activity
related studies suggested that both number and position of galloyls attached to 1,5-anhydro- -glucitol
were important for -glucosidase inhibition.
D-glucitol. The isolates were
a
D
a
l
Keywords:
Acer rubrum
Red maple
Maplexin
D
a
Ó 2011 Elsevier Ltd. All rights reserved.
Gallotannins
a-Glucosidase inhibitory
Diabetes is one of the most prevalent human diseases in the
with a
-glucosidase inhibitory activities.8–13 However, the red ma-
world. At least 220 million people suffer from diabetes worldwide
and this figure is estimated to double by 2030 (World Health Orga-
nization, 2010). Type 2 diabetes mellitus (also called non-insulin-
resistant diabetes mellitus) accounts for 90–95% of all diabetes
(Centers for Disease Control and Disease Prevention, 2010), which
is characterized by insulin resistance, relative insulin deficiency,
and hyperglycemia.1 Type 2 diabetes is associated with chronic
complications such as circulatory disease, stroke, hypertension,
blindness, kidney failure, uremia and gangrene of the lower limbs.2
At present, the therapies for type 2 diabetes rely mainly on several
anti-diabetic drugs including insulin itself, sulfonylureas, bigua-
ple is yet to be investigated for such effects. Recently various plant
part extracts of the red maple have been shown to have potent
antioxidant activities but the active compounds were not
identified.14
Our laboratory has reported on the identification and a-glucosi-
dase inhibitory activities of phenolic compounds isolated from ma-
ple syrup from Canada, from where the majority (ca. 85%) of the
world’s supply originates.15–18 In our ongoing efforts to discover
anti-diabetic compounds from natural sources, we initially
screened plant part extracts of various North American maple spe-
cies for
twigs extract inhibited
4–10 g/mL, prompting the current study.
a-glucosidase inhibitory activities. The red maple stems/
nides, thiazolidinediones and
a-glucosidase inhibitors. However,
a-glucosidase with IC50 values ranging from
several synthetic drugs have limited efficacy, limited tolerability
and significant side effects.3 Therefore, the search for natural prod-
ucts to serve as more effective antidiabetic drugs, with reduced
side effects, has attracted scientific interest.4–6
The red maple species (Acer rubrum L.) is native to eastern North
America and has been used for medicinal purposes by the Native
Americans.7 Both the red and sugar maple (Acer saccharum) species
are widely regarded for their sap which is concentrated to produce
maple syrup, a natural sweetener. Previous phytochemical studies
of some maple species have resulted in the isolation of gallotannins
l
Here we report the isolation and characterization of thirteen
gallic acid derivatives from red maple stems that include five
new gallotannins, compounds 2, 3, 5, 6, 9, assigned the common
names of maplexins A–E, respectively (Fig. 1). Also, the antioxidant
and a-glucosidase inhibitory properties, as well as structure–activ-
ity relationship (SAR) studies of the isolates are described herein.
The stems of red maple were extracted with methanol and par-
titioned sequentially with n-hexanes, EtOAc, and n-butanol. From
the EtOAc extract, thirteen gallic acid derivatives were isolated
by chromatographic methods,19 and their structures were charac-
terized using physicochemical and spectroscopic methods. The de-
tailed structural elucidation of the new compounds 2, 3, 5, 6, 9 are
described below and their 1H and 13C NMR data are shown in
Tables 1 and 2, respectively.
⇑
Corresponding authors. Tel.: +1 401 874 9367; fax: +1 401 874 5787.
E-mail addresses: myxie@ncu.edu.cn (M. Xie), nseeram@mail.uri.edu, nseer
am@uri.edu (N.P. Seeram).
These authors contributed equally.
0960-894X/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmcl.2011.10.073

598
C. Wan et al. / Bioorg. Med. Chem. Lett. 22 (2012) 597–600
O
OR1
O
OR4
O
6
4
5
R3O
R2O
R2O
OR4
1
HO
OH
1
2
3
OR
OR3
OH
Galloyl
1 R1 = Galloyl, R2 = R3 = R4 = H
2 R2 = Galloyl, R1 = R3 = R4 = H
3 R3 = Galloyl, R1 = R2 = R4 = H
4 R4 = Galloyl, R1 = R2 = R3 = H
5 R1 = R2 = Galloyl, R3 = R4 = H
6 R1 = R3 = Galloyl, R2 = R4 = H
7 R1 = R4 = Galloyl, R2 = R3 = H
8 R2 = R4 = Galloyl, R1 = R3 = H
9 R1 = R3 = R4 = Galloyl, R2 = H
10 R1 = R2 = R3 = R4 = H
11 R1 = CH3, R2 = R3 = R4 = H
12 R1 = R4 = CH3, R2 = R3 = H
13 R1 = R2 = R4= CH3, R3 = H
Figure 1. Structures of compounds 1–13.
Table 1
1H NMR [d, (multiplicity, JHH in Hertz)] spectroscopic data for compounds 2, 3, 5, 6 and 9a
No.
2
3
5
6
9
1ax
1eq
2
3
4
3.27 (1H, dd, 10.3, 9.9)
3.98 (1H, dd, 10.3, 5.8)
3.71 (1H, ddd, 9.9, 9.3, 5.8)
5.04 (1H, dd, 9.4, 9.3)
3.52 (1H, dd, 9.5, 9.4)
3.29 (1H, m)
3.24 (1H, dd, 10.8, 10.0)
3.99 (1H, dd, 10.8, 5.0)
3.58 (1H, m)
3.45 (1H, m)
4.89 (1H, overlap)
3.58 (1H, m)
3.45 (1H, dd, 10.9, 10.6)
4.20 (1H, dd, 10.9, 5.3)
5.08 (1H, m)
5.40 (1H, dd, 9.5, 9.3)
3.69 (1H, dd, 10.0, 9.5)
3.39 (1H, m)
3.40 (1H, dd, 10.9, 10.5)
4.18 (1H, dd, 10.9, 5.7)
4.99 (1H, m)
3.99 (1H, dd, 9.4, 9.3)
5.02 (1H, dd, 9.4, 8.9)
3.56 (1H, m)
3.46 (1H, dd, 11.5, 10.5)
4.22 (1H, dd, 11.5, 5.0)
5.02 (1H, m)
4.03 (1H, dd, 9.3, 9.2)
5.22 (1H, dd, 9.8, 9.3)
3.85 (1H, m)
5
6
3.85 (1H, dd, 11.9, 1.8)
3.66 (1H, dd, 11.9, 5.4)
7.14 (2H, d, 1.5)
—
3.58 (1H, m)
3.88 (1H, brd, 11.6)
3.72 (1H, dd, 11.6, 5.4)
7.05 (2H, d, 1.2)
6.96 (2H, d, 1.4)
—
3.61 (1H, brd, 9.9)
3.56 (1H, dd, 9.9, 5.6)
7.09 (2H, d, 1.1)
7.11 (2H, d, 1.0)
—
4.40 (1H, brd, 11.6)
4.19 (1H, dd, 11.6, 5.4)
7.11 (2H, d, 2.1)
7.11 (2H, d, 2.1)
7.08 (2H, d, 2.0)
3.49 (1H, dd, 11.3, 6.2)
7.09 (2H, d, 1.4)
—
20, 60
200, 600
2000, 6000
—
—
a
Data were measured in CD3OD at 500 MHz.
Table 2
13C NMR (d values) spectroscopic data for compounds 2, 3, 5, 6 and 9a
5.04 indicated the presence of a sugar substructure. Apart from
the galloyl carbon signals, six oxygenated carbon signals at dC
81.1, 79.8, 69.5, 68.6, 68.5 and 61.3 were observed in the 13C
NMR spectrum, which also supported the presence of a sugar moi-
ety. Further combined analysis of the 1H–1H COSY, HSQC and
HMBC spectra allowed the establishment of the structure of 2.
The HSQC spectrum allowed the assignment of all the protons at-
tached to their corresponding carbons. From the 1H–1H COSY spec-
trum, a 1-deoxysugar moiety (i.e., C-1 to C-6; Fig. 2a) was
established, and their relative stereochemistry was determined
by the proton coupling constants (J1ax,2 = 9.9 Hz, J2,3 = 9.3 Hz,
J3,4 = 9.4 Hz, J4,5 = 9.5 Hz). Thus, a 1-deoxysugar moiety was deter-
mined as 1,5-anhydro-glucitol. The HMBC correlations between H-
3 and the ester carbonyl (C-70) indicated that the galloyl group was
linked at C-3 of the 1,5-anhydro-glucitol moiety. Acid hydrolysis of
No.
2
3
5
6
9
1
2
3
4
5
6
69.5
68.5
79.8
68.6
81.1
61.3
69.6
70.2
79.5
71.4
76.4
61.4
66.4
70.0
76.5
68.5
81.3
61.2
66.6
71.9
73.5
71.4
79.6
61.2
66.6
71.8
73.5
71.1
76.8
62.7
1’
120.5
108.9
145.0
140.5
167.1
—
—
—
—
—
119.6
108.9
145.1
138.4
166.3
—
—
—
—
—
119.2
108.9
144.9
138.4
166.0
120.0
108.9
145.0
138.7
166.8
—
119.7
108.9
145.1
138.6
166.3
119.6
108.9
145.1
138.6
166.2
—
119.6
108.9
145.0
138.6
166.2
119.6
108.8
145.0
138.5
166.0
119.8
109.0
145.1
138.7
166.7
20, 60
30, 50
40
70
100
200, 600
300, 500
400
2 afforded 1,5-anhydro-
D-glucitol, which was identified by direct
700
1000
co-TLC comparison with an authentic sample. Therefore,
—
—
—
—
—
—
—
—
2000, 6000
3000, 5000
4000
—
—
—
—
—
—
—
—
OH
O
6
7000
—
—
OH
4
O
5
HO
HO
OH
1
a
Data were measured in CD3OD at 125 MHz.
2
3
OH
O
7'
7'
OH
O
Compound 2,20 a colorless amorphous solid, had a molecular
6
4
HO
O
5
O
formula of C13H16O9 determined by HRESIMS at m/z 315.0717
[MꢀH]ꢀ (calcd for C13H15O9, 315.0716). Its IR absorptions implied
the presence of ester carbonyl (1693 cmꢀ1) and aromatic ring
(1610 cmꢀ1). Inspection of the NMR data showed signals indicative
of galloyl moiety at dH 7.14 (s, 2H) and dC 167.1, 145.0 (2 ꢁ C),
140.5, 120.5, and 108.9 (2 ꢁ C). Eight proton signals at dH 3.27–
1
HO
OH
2
3
OH
OH
a
b
Figure 2. (a) 1H–1H COSY ( ) and key HMBC correlations (H?C) of 2; (b) 1H–1H
COSY ( ) and key HMBC correlations (H?C) of 3.

C. Wan et al. / Bioorg. Med. Chem. Lett. 22 (2012) 597–600
599
compound 2 was elucidated as 3-O-galloyl-1,5-anhydro-
assigned the common name of maplexin A.
D-glucitol,
aqueous layer was neutralized with Na2CO3 and then concentrated
to dryness. The concentrate was dissolved in methanol and puri-
Compound 3,21 had the same molecular formula as compound 2
(i.e., C13H16O9 as per HRESIMS data) as well as similar UV and IR
data. The 1H and 13C NMR spectra indicated the presence of similar
galloyl and 1,5-anhydro-glucitol substructures as for compound 2.
Further analyses of the 1H–1H COSY, HSQC and HMBC data showed
that the only difference between 2 and 3 was the linkage position
connecting the galloyl to the 1,5-anhydro-glucitol moiety. The gal-
loyl was eventually deduced to be attached to C-4 of the glucitol
substructure by the HMBC correlations from H-4 to C-70 (Fig. 2b).
fied by Sephadex LH-20 chromatography to give 1,5-anhydro-D-
glucitol, which was identified by co-TLC and specific rotation with
an authentic standard (Rf = 0.43, CHCl3–MeOH, 10:1 v/v, positive
value for optical rotation). The ESIMS and NMR data further sup-
ported these results.
Apart from the maplexins reported here, eight known com-
pounds were identified as ginnalins B (1),25 C (4),25 and A (7),26
3,6-di-O-galloyl-1,5-anhydro-D
-glucitol (8),12 gallic acid (10),27
methyl gallate (11),27 3,4-dihydroxy-5-methoxybenzoic acid
methyl ester (12)28 and methyl syringate (13)29 on the basis of
NMR and ESIMS data.
The
D-configuration of the glucitol was determined by the similar
acid hydrolysis method as described for compound 2. Compound
3 was thus determined as 4-O-galloyl-1,5-anhydro-D-glucitol as-
We investigated the in vitro
ties and the structure–activity relationship (SAR) of all thirteen iso-
lates. Compounds 5–9 and 11 were found to be inhibitors of
a
-glucosidase inhibitory16 proper-
signed the common name of maplexin B.
Compound 5,22 obtained as a colorless amorphous solid, had a
molecular formula of C20H20O13 as determined by HRESIMS at m/
z 467.0826 [MꢀH]ꢀ (calcd for C20H19O13, 467.0826). The 1H and
13C NMR data were similar to those of compounds 2 and 3, indicat-
ing that the structures of both compounds were closely related,
and the only difference was likely the presence of an additional
galloyl moiety in 5. Further analysis of the 2D NMR data allowed
the establishment of the structure of 5. In the HMBC spectrum,
the correlations from H-2 to C-70, and from H-3 to C-700 indicated
that the two galloyl groups were linked at C-2 and C-3 of 1,5-anhy-
a-
glucosidase enzyme in a concentration-dependent manner (Table
3). Compounds 1–4, which possess one galloyl group each, did
not show any activity in this assay, while compounds 5–8, which
possess two galloyl groups each, showed moderate
a-glucosidase
inhibitory activity. This is in agreement with a recent report sug-
gesting that the a-glucosidase inhibitory activities of gallotannins
are influenced by the number of their galloyl groups.10 Remark-
ably, maplexin E (9), which was the only isolate that contained
three galloyl groups, showed powerful
a-glucosidase inhibitory
dro-glucitol, respectively. The
D
-configuration of the glucitol was
activity. Maplexin E was 20 fold more potent than the known a-
determined by the same method as for compound 2. Compound
5 was therefore elucidated as 2,3-di-O-galloyl-1,5-anhydro-D-gluc-
glucosidase inhibitory drug, Acarbose (IC50 = 8.26 vs161.38
respectively).
lM,
itol assigned the common name of maplexin C.
Based on the
5–8 (IC50 = 1745.78, 1221.84, 95.38 and 88.42
a
-glucosidase inhibitory activities of compounds
Compound 6,23 had the same molecular formula (i.e.,
lM, respectively),
C20H20O13
)
as compound
5
based on the HRESIMS at m/z
which have two galloyl groups each, SAR inferences could be made.
467.0821 [MꢀH]ꢀ (calcd for C20H19O13, 467.0826). The IR and UV
spectra were also similar to 5. Initial analyses of the 1H and 13C
NMR data revealed the presence of two galloyl groups and a 1,5-
anhydro-glucitol moiety. The only difference between 6 and 5
was the linkage position of the galloyl to the 1,5-anhydro-glucitol
group. The two galloyl groups were finally assigned to attachment
at C-2 and C-4 of the 1,5-anhydro-glucitol on the basis of the HMBC
correlations from H-2 to C-70 and from H-4 to C-700, respectively.
Compounds 7 and 8 showed stronger activities than compounds 5
and 6, which suggested that the a-glucosidase inhibitory activities
of these gallotannins were influenced by both the number and
positions of the galloyl groups. Thus, it was apparent that a galloyl
group attached at the C-6 position of the 1,5 anhydro-glucitol moi-
ety increased activity.
The antioxidant activities of compounds 1–13 were evaluated in
the diphenylpicrylhydrazyl (DPPH) free radical scavenging assay.17
All of the isolates except 12 and 13 showed better antioxidant
activities than the positive controls, vitamin C, and the commercial
synthetic antioxidant, butylated hydroxytoluene (Table 3). The IC50
The
D-configuration of the glucitol was determined similar to that
for compound 2. Compound 6 was thus elucidated as 2,4-di-O-gal-
loyl-1,5-anhydro-
plexin D.
D-glucitol assigned the common name of ma-
values of compounds 1–4 ranged from 30.49 to 47.99 lM,
Compound 9,24 obtained as a colorless amorphous solid had a
molecular formula of C27H24O17 as determined by HRESIMS at
m/z 619.0916 [MꢀH]ꢀ (calcd for C27H23O17, 619.0935). From the
NMR spectra, three sets of signals for galloyl moieties, eight proton
signals at dH 3.46–5.22, and six oxygenated carbon signals at dC
76.8, 73.5, 71.8, 71.1, 66.6 and 62.7 were observed. The aforemen-
tioned data suggested that compound 9 was similar to the above
compounds, the only difference being the presence of three galloyl
groups attached to the 1,5-anhydro-glucitol moiety. The HMBC
correlations from H-2 to C-70, from H-4 to C-700, and from H2-6 to
C-7000 indicated that the three galloyl groups were linked at C-2,
Table 3
Antioxidant and
a
-glucosidase inhibitory activities of compounds 1–13
M)a
Compounds
IC50
(l
DPPH
a
-Glucosidase
1
2
3
4
5
6
7
8
32.70 0.48
47.99 1.11
45.57 1.45
30.49 0.80
18.80 0.77
18.59 0.77
17.74 0.21
18.52 0.44
13.06 0.16
20.39 0.34
16.49 0.26
116.50 4.98
990.57 80.60
71.02 1.61
1634.09 16.07
—
n.d.
n.d.
n.d.
n.d.
1745.78 168.05
1221.84 16.30
95.38 11.65
88.42 6.94
8.26 0.37
n.d.
317.39 3.70
6541.11 19.90
n.d.
C-4, and C-6 of the 1,5-anhydro-glucitol, respectively. The D-config-
uration of the glucitol was determined similar to that described for
compound 2. Compound 9 was thus elucidated as 2,4,6-tri-O-gal-
9
loyl-1,5-anhydro-
D
-glucitol assigned the common name of
10
11
12
13
maplexin E. To the best of our knowledge, this is the first gallotan-
nin reported to date that has three galloyl groups attached to three
different positions of a 1,5-anhydro-glucitol moiety.
Maplexins A–E (each 2 mg), were individually added to a mix-
ture of concentrated HCl (0.5 mL), H2O (2 mL) and dioxane (3 mL)
and refluxed for 2 h. After completion of the reaction (monitored
by TLC), the mixture was evaporated to dryness. The dry reaction
mixture was partitioned between CHCl3 and H2O (3 ꢁ 5 mL). The
b
Vitamin C
—
—
BHTb
Acarboseb
161.38 5.5
n.d. = not detected; BHT = butylated hydroxytoluene.
a
IC50 values are shown as mean S.D. from three independent experiments.
Positive control.
b

600
C. Wan et al. / Bioorg. Med. Chem. Lett. 22 (2012) 597–600
10. Ogawa, A.; Miyamae, Y.; Honma, A.; Koyama, T.; Yazawa, K.; Shigemori, H.
compounds 5–8 ranged from 17.74 to 18.80 lM, and compound 9
was 13.06 lM. These results suggested that the antioxidant activ-
ity of these gallotannins were influenced mainly by the number
Chem. Pharm. Bull. 2011, 59, 672.
11. Honma, A.; Koyama, T.; Yazawa, K. Food Chem. 2010, 123, 390.
12. Kumamoto, O. Chem. Pharm. Bull. 1960, 8, 72.
13. Koyama, T.; Honma, A.; Yazawa, K. J. Wood Sci. 2010, 56, 507.
14. Royer, M.; Diouf, P. N.; Stevanovic, T. Food Chem. Toxicol. 2011, 49, 2180.
15. Li, L.; Seeram, N. P. J. Funct. Foods 2011, 3, 125.
16. Apostolidis, E.; Li, L.; Lee, C.; Seeram, N. P. J. Funct. Foods 2011, 3, 100.
17. Li, L.; Seeram, N. P. J. Agric. Food Chem. 2011, 59, 7708.
18. Li, L.; Seeram, N. P. J. Agric. Food Chem. 2010, 58, 11673.
19. The dried stems (500 g) of Red maple species were ground and extracted
exhaustively with methanol. The combined dried methanol extract was re-
suspended in water and partitioned successively with n-hexanes, EtOAc and n-
of the galloyl groups, while the location of the galloyl group on
the 1,5-anhydro-
dant potential.
D-glucitol moiety was less important for antioxi-
In conclusion, we have identified thirteen compounds including
five new gallotannins, named maplexins A–E, from red maple with
a-glucosidase inhibitory potential. A new a-glucosidase inhibitory
gallotannin, named pycnalin, has recently been identified from the
Japanese red maple, Acer pycnanthum.10 Our SAR results are in
agreement with that study10 suggesting that the number of galloyl
butanol. The EtOAc fraction (18 g) was subjected to
a silica gel column
chromatography (CHCl3/MeOH) to yield three fractions (A1–A3). Fraction A3
(8 g) was chromatographed on a Sephadex LH-20 column and eluted with
MeOH to give seven sub-fractions (B1–B7). Fraction B4 was chromatographed
on a C18 MPLC column eluting with a gradient system of MeOH/H2O (1:9 to
7:3, v/v) to afford 14 sub-fractions (C1–C14). Fraction C2 was separated by semi-
preparative HPLC eluted with MeOH/H2O (20/80 v/v, 3.2 mL/min) to yield
compounds 2 (2.8 mg), 3 (2.5 mg) and 10 (460 mg). Fraction C3 was separated
by semi-preparative HPLC eluted with MeOH/H2O (25/75 v/v, 3.2 mL/min) to
yield compounds 1 (18 mg) and 4 (9.2 mg). Fraction C5 was separated by semi-
preparative HPLC eluted with MeOH/H2O (30/70 v/v, 3.2 mL/min) to yield
compounds 5 (5.3 mg) and 11 (7.7 mg). Fraction C6 was separated by semi-
preparative HPLC eluted with MeOH/H2O (27/73 v/v, 3.2 mL/min) to yield
compound 6 (25 mg). Fraction C9 was separated by semi-preparative HPLC
eluted with MeOH/H2O (25/75 v/v, 3.2 mL/min) to yield compounds 7 (13 mg)
and 12 (4.6 mg). Fraction C12 was separated by semi-preparative HPLC eluted
with MeOH/H2O (41/59 v/v, 3.2 mL/min) to yield compound 13 (0.8 mg).
Fraction B6 was chromatographed on a C18 MPLC column eluting with a
gradient system of MeOH/H2O (2:8 to 7:3, v/v) to afford 10 sub-fractions (D1–
groups attached to the 1,5-anhydro-
inhibition of -glucosidase. However, we have now demonstrated
that both number and location of the galloyl groups on the
1,5-anhydro- -glucitol moiety are important for activity. Thus,
synthetic manipulation of these gallotannins may result in com-
pounds with enhanced -glucosidase inhibitory potential. How-
D-glucitol are important for
a
D
a
ever, whether these natural compounds could serve as potential
therapeutic agents for type-2 diabetes would require further
studies.
Acknowledgments
This project was supported by funding provided by Agriculture
and Agri-Food Canada through the Developing Innovative Agri-
Products (DIAP) initiative. The Federation of Maple Syrup Produc-
ers of Quebec participated in the collection of plant materials from
Quebec, Canada. The authors would like to thank Mr. J. Peter Mor-
gan and Dr. Emmanouil Apostolidis for assistance with plant
D
10). Fraction D1 was separated by semi-preparative HPLC eluted with MeOH/
H2O (30/70 v/v, 3.2 mL/min) to yield compound 8 (1.4 mg). Fraction D8 was
separated by semi-preparative HPLC eluted with MeOH/H2O (35/65 v/v,
3.2 mL/min) to yield compound 9 (5 mg).
20. 3-O-galloyl-1,5-anhydro-
D
-glucitol (2): colorless amorphous solid; ½a2D0ꢂ +25 (c
0.280, MeOH); UV (MeOH) kmax (loge): 276 (4.10), 216 (4.41) nm; IR mmax 1693,
1610 cmꢀ1; for 1H NMR and 13C NMR data, see Tables 1 and 2, respectively;
HREIMS at m/z 315.0717 [MꢀH]ꢀ (calcd for C13H15O9, 315.0716).
authentication and conduction of the
say, respectively.
a-glucosidase inhibitory as-
21. 4-O-galloyl-1,5-anhydro-
D
-glucitol (3): colorless amorphous solid; ½a2D0ꢂ +15 (c
0.060, MeOH); UV (MeOH) kmax (loge): 276 (4.10), 216 (4.41) nm; IR mmax 1690,
1608 cmꢀ1; for 1H NMR and 13C NMR data, see Tables 1 and 2, respectively;
HREIMS at m/z 315.0719 [MꢀH]ꢀ (calcd for C13H15O9, 315.0716).
Supplementary data
22. 2,3-di-O-galloyl-1,5-anhydro-
D
-glucitol (5): colorless amorphous solid; ½a2D0ꢂ +13
(c 0.120, MeOH); UV (MeOH) kmax (loge): 276 (4.10), 216 (4.41) nm; IR mmax
1705, 1600 cmꢀ1 for 1H NMR and 13C NMR data, see Tables
; 1 and 2,
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.bmcl.2011.10.073.
respectively; HREIMS at m/z 467.0826 [MꢀH]ꢀ (calcd for C20H19O13, 467.0826).
23. 2,4-di-O-galloyl-1,5-anhydro-
D
-glucitol (6): colorless amorphous solid; ½a2D0ꢂ +6
(c 0.170, MeOH); UV (MeOH) kmax (loge): 276 (4.10), 216 (4.41) nm; IR mmax
1703, 1601 cmꢀ1 for 1H NMR and 13C NMR data, see Tables
; 1 and 2,
References and notes
respectively; HREIMS at m/z 467.0821 [MꢀH]ꢀ (calcd for C20H19O13, 467.0826).
24. 2,4,6-tri-O-galloyl-1,5-anhydro-
D
-glucitol (9): colorless amorphous solid; ½aD20
ꢂ
1. Moller, D. E. Nature 2001, 414, 821.
2. Israili, Z. H. Am. J. Ther. 2011, 18, 117.
+10 (c 0.130, MeOH); UV (MeOH) kmax (loge): 276 (4.10), 216 (4.41) nm; IR
mmax 1710, 1598 cmꢀ1; for 1H NMR and 13C NMR data, see Tables 1 and 2,
respectively; HREIMS at m/z 619.0916 [MꢀH]ꢀ (calcd for C27H23O17, 619.0935).
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