Synthesis of acyl derivatives of salicin, salirepin, and arbutin

Article abstract of DOI:10.1016/j.carres.2014.02.014

The total synthesis of two natural phenolglycosides of the family Salicaceae, namely: populoside and 2-(β-d-glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-4-hydroxy) cinnamoate and nine not found yet in plants acyl derivatives of phenoglycosides: 2-(β-d-glucopyranosyloxy)-benzylcinnamoate, 2-(β-d-glucopyranosyloxy)-benzyl (4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-benzyl (3-methoxy-4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-5-hydroxy benzyl (3,4-dihydroxy) cinnamoate, 2-(β-d-glucopyranosyloxy)-5-hydroxy benzylcinnamoate, 2-(β-d- glucopyranosyloxy)-5-hydroxy benzyl (4-hydroxy) benzoate, 2-(β-d- glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-4-hydroxy) benzoate, 2-(β-d-glucopyranosyloxy)-5-benzoyloxy benzylbenzoate and 4-(β-d-glucopyranosyloxy)-phenylbenzoate, starting from readily available phenols and glucose was developed for the first time.

Full text of DOI:10.1016/j.carres.2014.02.014

Carbohydrate Research 388 (2014) 105–111
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of acyl derivatives of salicin, salirepin, and arbutin
⇑
Elena V. Stepanova , Maxim L. Belyanin, Victor D. Filimonov
Department of Biotechnology and Organic Chemistry, National Research Tomsk Polytechnic University, 30 Lenin Avenue, Tomsk 634050, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
The total synthesis of two natural phenolglycosides of the family Salicaceae, namely: populoside and
Received 15 October 2013
Received in revised form 9 February 2014
Accepted 10 February 2014
Available online 20 February 2014
2-(b-
yet in plants acyl derivatives of phenoglycosides: 2-(b-
2-(b- -glucopyranosyloxy)-benzyl (4-hydroxy) benzoate, 2-(b-
oxy-4-hydroxy) benzoate, 2-(b- -glucopyranosyloxy)-5-hydroxy benzyl (3,4-dihydroxy) cinnamoate,
2-(b- -glucopyranosyloxy)-5-hydroxy benzylcinnamoate, 2-(b- -glucopyranosyloxy)-5-hydroxy benzyl
(4-hydroxy) benzoate, 2-(b- -glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-4-hydroxy) benzoate,
2-(b- -glucopyranosyloxy)-5-benzoyloxy benzylbenzoate and 4-(b- -glucopyranosyloxy)-phenylbenzo-
ate, starting from readily available phenols and glucose was developed for the first time.
Ó 2014 Elsevier Ltd. All rights reserved.
D
-glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-4-hydroxy) cinnamoate and nine not found
-glucopyranosyloxy)-benzylcinnamoate,
-glucopyranosyloxy)-benzyl (3-meth-
D
D
D
D
D
D
Keywords:
Phenolic acyl glycosides
Populoside
Salirepin derivatives
Salicin derivatives
Benzoylarbutin
D
D
D
1. Introduction
ion-caffeic acid complexes.12 Ferulic acid has antioxidant, antimi-
crobial, anti-inflammatory, anti-thrombosis, and anti-cancer activ-
ities.13 para-Hydroxybenzoic acid, basic component of parabenes,
shows antimicrobial activity,14 antifungal, antimutagenic, antisic-
kling, and estrogenic activity.15 Vanillic acid has hepatoprotective
effect16,17 and exerts protective effects on cardiotoxic organisms.18
Thus, the structure of glycosides containing different combina-
tions of salicin or salirepin moiety and one or more phenolic acids
is the most predictable (Fig. 1). For confirmation of this, new
phenolglycoside, consisting of salirepin and caffeic acid (19) was
recently isolated.6
We previously reported the synthesis of some natural phenol-
glycosides of the family Salicaceae, containing cinnamic acids,
namely, populosides A, B, and C.19 We suggested a simple synthetic
pathway for phenolglycosides of different structures. Thus, it
would be reasonable to obtain glycosides of expected structure if
they were not isolated from natural sources yet to make easier fur-
ther phytochemical or biological investigations.
The existence of phenolic glycosides in plants has been known
for many years. The first, Salicin, was isolated in 1828 from willow
bark.1 Since then, many glycosides of different structures were iso-
lated and identified.2 These substances are of great interest for
medicinal use because of their diverse biological activities. Plants
of the family Salicaceae with large phenolglycoside content are
widely used in traditional medicines all over the world and helpful
for cure of pox, variola, pulmonary disease,3 arthritis,4 and other
diseases. Most of phenolglycosides have anti-inflammatory activ-
ity5 and antioxidant activity.6,7
The structure of Salicaceae phenolglycosides includes salicin
(glucoside of salicylic alcohol) or salirepin (glucoside of gentisinic
alcohol) acylated by different benzoic or cinnamic acids. It is not
absolutely clear yet, but biological effects of phenolglycosides are
more likely caused by the aglycon and especially by the nature of
phenolic acid.
The presence of several phenolic acids in hydrolyzed methanol
extracts from different species of Salix was established,8 namely,
p-hydroxybenzoic, vanillic, cinnanic, p-coumaric, ferulic, and caf-
feic acids. Obviously, such acids exist as free or as parts of
glycosides.9
Indeed, it is known, that caffeic acid has anti-inflammatory and
analgesic activity.10 It has been found to be pharmacologically
active as an antioxidant, antimutagenic, anticarcinogenic agent,
and as a lipoxygenase inhibitor11 and forms transitional metal
2. Results and discussion
The initial glycoside 1 was easily obtained by bromination of
tetra-O-acetyl-o-cresylglycoside, which, in turn, was obtained by
glycosylation of o-cresole.20 Glycosides 2, 3, and 4 were obtained
according to the method described previously.19 Acylation of 1
was carried out by phenolic acids with sodium hydrocarbonate in
DMF21 medium (Scheme 1). Acyl-glycosides 5–6 were obtained in
good yields.
Acylation of compound 2, 3, and 4 was carried out by acyl chlo-
ride of proper acid with pyridine to produce glycosides 7–14.
⇑
Corresponding author. Tel.: +7 8 (3822) 56 38 61; fax: +7 8 (3822) 56 36 37.
E-mail address: eline_m@mail.ru (E.V. Stepanova).
http://dx.doi.org/10.1016/j.carres.2014.02.014
0008-6215/Ó 2014 Elsevier Ltd. All rights reserved.

106
E. V. Stepanova et al. / Carbohydrate Research 388 (2014) 105–111
OH
OH
3
5
2
2
3
6'
6'
HO4'
4'
O
O
2'OH
1
1
O
HO
R
1'
O
1'
R
HO
HO
2'OH
3'
3'
5
13
O
O
7
7
OH
9
15
16
12
8
2
6
3
R1
6'
4'
O
2'OH
1
R1
O
11
O
11 10
10
HO
O
1'
O
HO
R2
12
15
16
17
3'
R=H, R1=R2=OH, 15
R=R1=R2=H, 16
O
R2
R=R2=H, R1=OH, 17
R=H, R1=OH,R2=OCH3, 18
27
R=R1=R2=OH, 19
R=OH, R1=R2=H, 20
21
R=R1=OH, R2=H,
19
18
R=R1=OH, R2=OCH3,22
R=R1=OH, R2=OCH3, 23
R=OCOPh,R1=R2=H, 24
Figure 1. Structure of synthesized phenolglycosides 15–24, 27.
OAc
OAc
OH
O
O
O
AcO
AcO
AcO
O
R
HO
HO
O
R
c
O
R
a-b
AcO
OAc
OAc
OH
OR1
OR1
R1
R=H R1=Br, 1
R=H R1=3,4-diacetoxycinnamoyl, 5 (78%)
R=H, R1=cinnamoy l6 (65%)
R=H R1=3,4-dihydroxycinnamoyl,15 (50%)
R=H, R1=cinnamoyl 16 (40%)
R=H, R1=4-hydroxybenzoyl, 17 (80%)
R=H, R1=3-methoxy-4-hydroxybenzoyl, 18 (35%)
R=OH R1=3,4-dihydroxycinnamoyl, 19 (30%)
R=OH R1=cinnamoyl, 20 (34%)
R=OAc, R1=OH, 2
R=H, R1=OH, 3
R=H, R1=4-acetoxybenzoyl, 7 (53%)
R=OCOPh, R1=OH,4
R=H, R1=3-methoxy-4-acetoxybenzoyl, 8 (66%)
R=OAc, R1=3,4-diacetoxycinnamoyl, 9 (85%)
R=OAc, R1=cinnamoyl, 10 (40%)
R=OAc, R1=4-acetoxybenzoyl, 11 (52%)
R=OH, R1=4-hydrxybenzoyl 21 (55%)
R=OAc, R1=3-methoxy-4-acetoxybenzoyl, 12 (70%) R=OH, R1=3-methoxy-4-hydroxybenzoyl, 22 (36%)
R=OAc, R1=4-acetoxy-3-methoxycinnamoyl, 13 (60%) R=OH R1=4-hydroxy-3-methoxycinnamoyl, 23 (48%)
R=OCOPh, R1=benzoyl, 14 (77%)
R=OCOPh, R1=benzoyl, 24 (60%)
Scheme 1. Synthesis of 2-acyl phenolglycosides. Reagents and conditions: (a) acyl chloride of proper acid (3,4-acetoxy cinnamoyl chloride, cinnamoyl chloride, 4-acetoxy-3-
methoxy cinnamoyl chloride, 4-acetoxybenzoyl chloride, 3-methoxy-4-acetoxy chloride, benzoylchloride), pyridine, CHCl3, 24 h, 20 °C; (b) proper acid (3,4-acetoxy cinnamic
acid, cinnamic acid, 4-acetoxybenzoic acid, 3-methoxy-4-acetoxybenzoic acid), NaHCO3, DMF, RT, 24 h; (c) 36% HCl, CHCl3, EtOH (1:1:3), 8–13 h, 30 °C.
OH
OH
OAc
O
O
c
O
d
O
HO
HO
O
O
AcO
AcO
O
O
O
OH
OAc
27
26
25
O
Scheme 2. Synthesis of benzoyl-arbutin. Reagents and conditions: (d) acetobromoglucose, quinoline, Ag2O, RT, 1 h; (c) as in the Scheme 1.
For the selective cleavage of acetyl groups in the presence of
other acyl groups we applied the system, suggested previously:
HCl–EtOH (96%)-chloroform in a molar ratio of HCl-glycoside
54:1. The reaction at 30 °C for 8–13 h resulted in successful acetyl
group cleavage without significant cleavage of labile phenacyl
groups and without breaking the glycosidic bond. All resulted
glycosides 15–24 had b-configuration of anomeric center and
trans-configuration of double bond esters of cinnamic acids
(J = 15.9–16.2 Hz). Physicochemical data for populoside 15, and
glycoside 19 matched those reported.6,22,23
is used in cosmetic industry.26 Several attempts of 60-O-benzoylar-
butin synthesis were taken both by chemical27,28 and enzymatic29
means, but obtaining arbutin with aglycon benzoyl group 26 has
not been previously reported.
In conclusion, we performed the first total synthesis of two
known natural phenolglycosides, namely, populoside 15 and caffeoyl
salirepin 19. The resulted substances are identical to natural samples
according to their physico-chemical properties. We also synthesized
nine phenolglycosides of expected structure 15–17, 19–23, 26 that
could be found in Salicaceae and have biological activity.
Glycoside 24, 5-benzoylsalireposide, is isomeric to natural com-
pound, 30-benzoylsalireposide, found in Symplocos racemosa.24 Nat-
ural compound showed strong inhibitory activity against snake
venom phosphodiesterase I. Thus, substance 24 has potentially
the same biological activity.
3. Experimental
3.1. General experimental procedures
We also obtained benzoyl-arbutin 27 (Scheme 2), from acetate
26. Substance 26 is well-known intermediate product for produc-
tion of arbutin25 and forms by glycosylation of monobenzoylhy-
droquinone 25. Arbutin is natural phenolglycoside that nowadays
Melting points, which are uncorrected, were determined using
MP50 Melting point system (Mettler toledo). UV spectroscopic data
were obtained with SF-102 spectrophotometer. IR spectra were
recorded with IR Fourier spectrophotometer Spectrum BX II using

E. V. Stepanova et al. / Carbohydrate Research 388 (2014) 105–111
107
KBr disks. The 1H and 13C NMR spectra were recorded on Bruker-300
3.4.1. 2-(2,3,4,6-Tetra-O-acetyl-b-
D-glucopyranosyloxy)-benzyl
spectrometer at 300 and 75.5 MHz, respectively, in CDCl3, DMSO-d6,
and MeOD-d4 with TMS as an internal standard and Cr(acac)3 as a
relaxant. The chemical shifts are given in d (ppm) and the spinꢀspin
coupling constants (J) in hertz. Elemental analysis was performed
on a EuroEA-3000 CHNS-O elemental analyzer. GC–MS analysis
was performed using Aligent 7890A/5975C GC/MSD instrument,
electron energy 70 eV. The ion source temperature was 230 °C, with
the quadrupole temperature 150 °C and evaporator temperature
(3,4-diacetoxy) cinnamoate (populoside hexaacetate) (5)
The compound 5 was obtained from 3,4-diacetoxy cinnamic
acid. Yield 78%, mp 93–94 °C, lit.22 93–95 °C. UV kmax (EtOH)/nm:
279. IR (KBr,
m
max/cmꢀ1): 2960, 1760, 1640, 1380, 1240, 1040,
907, 760. 1H NMR (CDCl3, 300 MHz) d: 2.04, 2.06, 2.09, 2.12, 2.30
(s, 6 ꢁ 3H, Ac), 3.88 (m, 1H, H-50), 4.16 (d, 1H, J = 10.8 Hz, H-60b),
4.25 (dd, 1H, J = 5.0, 12.3 Hz, H-60a), 5.08 (m, 1H, H-10), 5.15–5.22
(m, 2H, H-40, H-30), 5.26–5.32 (m, 3H, H-20, 2H-7), 6.35 (d, 1H,
J = 15.9 Hz, H-9), 7.08 (m, 2H, H-2, H-4), 7.20 (d, 1H, J = 8.4 Hz,
H-15), 7.26 (m, 2H, H-3, H-5), 7.36 (m, 2H, H-12, H-16), 7.62 (d,
1H, J = 16.2 Hz, H-10). 13C NMR (CDCl3, 75.5 MHz) d: 20.7
(6 ꢁ CH3, Ac), 61.2 (CH2, C60), 61.9 (CH2, C-7), 68.3 (CH, C-40),
71.0 (CH, C-20), 72.0 (CH, C-30), 72.6 (CH, C-50), 99.3 (CH, C-10),
115.9 (CH, C-2), 119.0 (CH, H-9), 122.8 (CH, C-15), 123.6 (CH,
C-4), 124.0 (CH, C-12), 126.2 (CH, C-6), 126.5 (CH,C-16), 129.5
(2 ꢁ CH, C-3, C-5), 133.2 (C, C-11), 142.4 (C, C-13), 143.2 (CH,
C-10), 143.5 (C, C-14), 154.5 (C, C-1), 166.3 (C@O, C-8), 168.1,
169.4, 170.3 (6 ꢁ C@O, Ac).
315 °C, employing a 30.000 ꢁ 0.25 mm ꢁ 0.25
lm HP—5MS fused-
silica capillary column. Helium was used as carrier gas at a constant
flow of 1 mL/min and an inlet temperature of 315 °C. The column
temperature was initially held at 150 °C for 2 min and then the tem-
perature was raised to 315 °C at a rate of 20 °C/min, followed by iso-
thermal period of 25 min. The total run time was 35.25 min. TLC was
performed using plates Silica gel 60 F254 Merck and Sorbfil-UV 254
using benzene-ethanol 9:1 (method A) or chloroform-methanol 4:1
(B) mixtures as eluents. HPLC analysis was carried out with the
liquid chromatographer Agilent Compact LC with column
150 ꢁ 4.6 Exlips Plus C-18 (5
lm). Analysis was performed using
0.1% trifluoroacetic acid in H2O–CH3CN as mobile phase, at gradient
3.4.2. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-
benzylcinnamoate (6)
elution (from 0% to 100% CH3CN in 20 min) at a flow rate of
1 mL/min. Probe volume was 20 lL. UV detection was performed
at 220 nm. Accurate mass measurement was performed on an
Agilent 1200 series LC system coupled with an Agilent 6210 TOF
mass spectrometer. Silica gel MN Kieselgel 60 0.04–0.063 mm was
used for column chromatography. Commercially available solvents
were used after drying with CaCl2.
The compound 6 was obtained from cinnamic acid. Yield 65%,
mp 116–118 °C. UV kmax (EtOH)/nm: 278. IR (KBr,
m
max/cmꢀ1):
1750, 1640, 1500, 1370, 1210, 1030, 907. 1H NMR (CDCl3,
300 MHz) d: 2.03, 2.04, 2.06, 2.09 (s, 4 ꢁ 3H, Ac), 3.85 (m, 1H,
H-50), 4.16 (d, 1H, J = 12.3 Hz, H-60b), 4.25 (dd, 1H, J = 5.0,
12.3 Hz, H-60a), 5.09 (d, 1H, J = 7.2, Hz, H-10), 5.14–5.20 (m, 2H,
H-40, H-30), 5.27–5.30 (m, 3H, H-20, 2H-7), 6.45 (d, 1H, J = 15.3 Hz,
H-9), 6.94 (m, 2H, H-2, H-4), 7.29 (m, 1H, H-5), 7.36 (m, 4H, H-3,
H-13, H-14, H-15), 7.50 (m, 2H, H-12, H-16), 7.69 (d, 1H,
J = 15.9 Hz, H-10). 13C NMR (CDCl3, 75.5 MHz) d: 20.3 (4 ꢁ CH3,
Ac), 60.7 (CH2, C60), 61.6 (CH2, C-7), 68.0 (CH, C-40), 70.7 (CH,
C-20), 71.7 (CH, C-30), 72.3 (CH, C-50), 99.1 (CH, C-10), 115.6 (CH,
C-2), 117.6 (CH, H-9), 123.3 (CH, C-4), 126.1 (C, C-6), 127.8
(2 ꢁ CH, C-12, C-16), 128.6 (2 ꢁ CH, C-13, C-15), 129.2 (CH,C-3),
129.8 (CH, C-5), 130.1 (CH, C-14), 134.0 (C, C-11), 144.8 (CH,
C-10), 154.2 (C, C-1), 166.3 (C@O, C-8), 169.0, 169.9, 170.2
(4 ꢁ C@O, Ac). Anal. Calcd for C30H32O12: C, 61.64; H, 5.52. Found:
C, 61.48; H, 5.50.
3.2. 2-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyloxy)-benzyl
bromide (1)
The compound 1 was obtained according to20 by gylcosylation of
o-cresole and further radical bromination of 2-(2,3,4,6-tetra-O-
acetyl-b-
D
-glucopyranosyloxy)-toluene. Total yield 16% from o-cre-
sole, mp 150–151 °C. UV kmax (EtOH)/nm: 277. IR (KBr,
m
max/cmꢀ1):
2960, 1750, 1603, 1490, 1380, 1240, 1210, 1040, 108, 755. 1H NMR
(DMSO-d6, 300 MHz) d: 1.98, 2.01, 2.04 (s, 4 ꢁ 3H, Ac), 4.07 (m, 1H,
H-50), 4.21–4.30 (m, 2H, H-60b, H-7b), 4.49–4.58 (m, 2H, C-60a, C-7a),
4.99 (t, 1H, J = 9.6 Hz, H-40), 5.12 (m, 1H, H-30), 5.41 (m, 1H, H-20),
5.56 (d, 1H, J = 7.8 Hz, H-10), 7.06 (m, 2H, H-2, H-4), 7. 32 (m, 1H,
H-3), 7.42 (d, 1H, J = 7.8 Hz, H-5). 13C NMR (DMSO-d6, 75.5 MHz)
d: 20.4 (4 ꢁ CH3, Ac), 28.9 (CH2, C-7), 61.8 (CH2, C-60), 68.0 (CH, C-
40), 70.2 (CH, C-20), 70.9 (CH, C-30), 71.8 (CH, C-50), 97.0 (CH, C-10),
114.9 (CH, C-2), 122.9 (CH, C-4), 126.5 (C, C-3), 130.2 (CH, C-6),
131.2 (CH, C-5), 154.1 (C, C-1), 169.0, 169.2, 169.4, 169.9 (4 ꢁ C, Ac).
3.5. Acylation of glycoside 2, 3, and 4. General method
To a solution of glycoside 2,3, or 4 (0.2 mmol) in 1 mL CHCl3,
0.22 mmol of acyl chloride and 0.26 mmol of pyridine were added.
The reaction mixture was kept at room temperature for 24 h and
diluted with 20 mL CHCl3. The solution was washed with 0.1 M
H2SO4, satd Na2CO3, water, dried over Na2SO4 and evaporated.
The residue was recrystallized from ethanol.
3.3. 2-(2,3,4,6-Tetra-O-acetyl-b-
oxy benzyl alcohol (2), 2-(2,3,4,6-tetra-O-acetyl-b-
pyranozyloxy)-benzyl alcohol (3) and 2-(2,3,4,6-tetra-O-acetyl-
D-glucopyranozyloxy)-5-acetyl-
D
-gluco-
3.5.1. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-benzyl
(4-acetoxy) benzoate (7)
b-
D-glucopyranozyloxy)-5-benzoyloxy benzyl alcohol (4)
The compound 7 was obtained from 4-acetoxy benzoic acid and
glycoside 3. Yield 53%, mp 135–137 °C. UV kmax (EtOH)/nm: 235. IR
The compounds 2, 3, and 4 were obtained according to the
(KBr, m
max/cmꢀ1): 1740, 1730, 1600, 1370, 1210, 1040, 910, 750. 1H
method described earlier.19
NMR (CDCl3, 300 MHz) d: 2.03, 2.04, 2.05, 2.07, 2.31 (s, 5 ꢁ 3H, Ac),
3.84–3.88 (m, 1H, H-50), 4.16 (dd, 1H, J = 2.1, 12,3 Hz, H-60b), 4.25
(dd, 1H, J = 5.1, 12.3 Hz, H-60a), 5.11 (d, 1H, J = 7.2 Hz H-10), 5.15
(m, 1H, H-40), 5.25–5.44 (m, 2H, H-20, H-30), 5.30 (m, 2H, H-7),
7.11 (m, 2H, H-2, H-4), 7.16 (d, 2H, J = 8.4 Hz, H-11, H-13), 7.29
(m, 1H, H-3), 7.40 (d, 1H, J = 7.2 Hz, H-5), 8.09 (d, 2H, J = 8.4 Hz,
H-10, H-14). 13C NMR (CDCl3, 75.5 MHz) d: 20.6, 21.2 (5 ꢁ CH3,
Ac), 61.5 (CH2, C60), 61.9 (CH2, C-7), 68.4 (CH, C-40), 71.1 (CH,
C-20), 72.1 (CH, C-30), 72.7 (CH, C-50), 99.4 (CH, C-10), 116.0 (CH,
C-2), 121.7 (2 ꢁ CH, C-11, C-13), 123.6 (CH, C-4), 126.4 (C, C-6),
127.7 (C, C-9), 129.3 (C, C-3), 129.4 (C, C-5), 131.3 (2 ꢁ CH, C-10,
C-14), 154.4 (C, C-1), 154.5 (C, C-12), 165.4 (C@O, C-8), 168.8,
3.4. Alkylation of glycoside 1. General method
A mixture of 0.150 g (0.29 mmol) of glycoside 1, 0.35 mmol of
proper acid, 0.35 mmol of sodium bicarbonate, and 1 mL of DMF
was stirred at room temperature for 24–48 h. After reaction was
complete (HPLC control), the reaction mixture was poured into
5 mL of water and stirred until obtained glycoside precipitated,
filtered and recrystallized from ethanol. If glycoside did not precip-
itate, it was extracted twice with CHCl3. CHCl3 layer was washed
with satd Na2CO3, water, dried over Na2SO4, and evaporated. The
residue was recrystallized from ethanol.

108
E. V. Stepanova et al. / Carbohydrate Research 388 (2014) 105–111
169.4, 170.2, 170.5 (5 ꢁ C@O, Ac). Anal. Calcd for C30H32O14: C,
3.5.5. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-5-
acetoxy benzyl (4-acetoxy) benzoate (11)
58.44; H, 5.23. Found: C, 58.31; H, 5.39.
The compound 11 was obtained from 4-acetoxy benzoyl chlo-
ride and glycoside 4. Yield 52%, mp 93–94 °C. UV kmax (EtOH)/
3.5.2. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-benzyl
(3-methoxy-4-acetoxy) benzoate (8)
nm: 232, 274. IR (KBr, m
max/cmꢀ1): 1750, 1640, 1600, 1500, 1370,
The compound 8 was obtained from 3-methoxy-4-acetoxy ben-
1210, 1190, 1030, 906. 1H NMR (CDCl3, 300 MHz) d: 2.03, 2.04,
2.07, 2.10, 2.28, 2.32 (s, 6 ꢁ 3H, Ac), 3.81–3.86 (m, 1H, H-50), 4.16
(dd, 1H, J = 2.1, 12,3 Hz, H-60b), 4.25 (dd, 1H, J = 5.1, 12.3 Hz, H-
60a), 5.02 (d, 1H, J = 7.2 Hz H-10), 5.14 (m, 1H, H-40), 5.20–5.41
(m, 2H, H-20, H-30), 5.28 (m, 2H, H-7), 7.02 (dd, 1H, J = 2.7, 8.7 Hz,
H-3), 7.08. 13C NMR (CDCl3, 75.5 MHz) d: 20.5, 21.1 (6 ꢁ CH3, Ac),
60.9 (CH2, C60), 61.7 (CH2, C-7), 68.1 (CH, C-40), 70.9 (CH, C-20),
72.0 (CH, C-30), 72.5 (CH, C-50), 99.7 (CH, C-10), 117.1 (CH, C-2),
121.6 (2 ꢁ CH, C-11, C-13), 121.8 (CH, C-3), 122.1 (CH, C-5),
127.5 (C, C-9), 127.8 (C, C-6), 131.2 (2 ꢁ CH, C-10, C-14), 146.2
(C, C-4), 151.5 (C, C-1), 154.3 (C, C-12), 165.0 (C@O, C-8), 168.7,
169.2, 169.5, 170.1, 170.5 (6 ꢁ C@O, Ac). Anal. Calcd for
zoic acid and glycoside 3. Yield 66%, mp 122–124 °C. UV kmax
(EtOH)/nm: 242, 291. IR (KBr,
m
max/cmꢀ1): 2950, 1740, 1600,
1370, 1240, 1050, 1040, 910, 750. 1H NMR (CDCl3, 300 MHz) d:
2.03, 2.05, 2.07, 2.34 (s, 5 ꢁ 3H, Ac), 3.88 (m, 1H, H-50), 3.88 (s,
3H, OCH3), 4.16 (dd, 1H, J = 2.1, 12,0 Hz, H-60b), 4.26 (dd, 1H,
J = 5.1, 12.3 Hz, H-60a), 5.09 (d, 1H, J = 7.5 Hz H-10), 5.14 (m, 1H,
H-40), 5.25–5.44 (m, 2H, H-20, H-30), 5.30 (m, 2H, H-7), 7.08 (m,
3H, H-2, H-4, H-13), 7.26 (m, 1H, H-3), 7.39 (d, 1H, J = 6.9 Hz, H-
5), 7.68 (s, 1H, H-10), 7.68 (dd, 1H, J = 1.2, 9.0 Hz, H-14). 13C NMR
(CDCl3, 75.5 MHz) d: 20.6 (5 ꢁ CH3, Ac), 56.2 (OCH3), 61.6 (CH2,
C60), 61.9 (CH2, C-7), 68.3 (CH, C-40), 71.0 (CH, C-20), 72.1 (CH, C-
30), 72.7 (CH, C-50), 99.5 (CH, C-10), 113.6 (CH, C-10), 115.9 (CH,
C-2), 122.7 (CH, C-4), 122.8 (CH, C-13), 123.7 (CH, C-14), 126.4
(CH, C-6), 128.9 (C, C-9), 129.3 (C, C-5), 129.4 (CH, C-3), 143.7 (C,
C-12), 151.1 (C, C-11), 154.5 (C, C-1), 165.6 (C@O, C-8), 168.5,
169.3, 169.4, 170.2, 170.6 (5 ꢁ C@O, Ac). Anal. Calcd for
C32H33O16: C, 56.97; H, 5.08. Found: C, 56.81; H, 5.01.
3.5.6. 2-(2,3,4,6-Tetra-O-acetyl-b- -glucopyranosyloxy)-5-
D
acetoxy benzyl (3-methoxy-4-acetoxy) benzoate (12)
The compound 12 was obtained from 3-methoxy-4-acetoxy
benzoyl chloride and glycoside 4. Yield 70%, mp 156–159 °C. UV
C
31H34O15: C, 57.58; H, 5.30. Found: C, 57.40; H, 5.55.
kmax (EtOH)/nm: 241, 285. IR (KBr, m
max/cmꢀ1): 1760, 1740, 1610,
3.5.3. 2-(2,3,4,6-Tetra-O-acetyl-b- -glucopyranosyloxy)-5-
acetoxy benzyl (3,4-diacetoxy) cinnamoate (9)
D
1380, 1220, 1050, 910, 760. 1H NMR (CDCl3, 300 MHz) d: 2.03,
2.05, 2.08, 2.28, 2.33 (s, 6 ꢁ 3H, Ac), 3.89 (m, 1H, H-50), 3.89 (s,
3H, OCH3), 4.16 (dd, 1H, J = 2.1, 12,3 Hz, H-60b), 4.25 (dd, 1H,
J = 5.1, 12.3 Hz, H-60a), 5.04 (d, 1H, J = 7.2 Hz H-10), 5.14 (m, 1H,
H-40), 5.24–5.42 (m, 2H, H-20, H-30), 5.29 (m, 2H, H-7), 6.99 (dd,
1H, J = 2.7, 8.7 Hz, H-3), 7.10 (m, 3H, H-2, H-5, H-13), 7.68 (m,
2H, H-10, H-14). 13C NMR (CDCl3, 75.5 MHz) d: 20.5, 21.0
(6 ꢁ CH3, Ac), 56.1 (OCH3), 61.0 (CH2, C60), 61.8 (CH2, C-7), 68.1
(CH, C-40), 70.9 (CH, C-20), 72.0 (CH, C-30), 72.5 (CH, C-50), 99.7
(CH, C-10), 113.5 (CH, C-10), 117.0 (CH, C-2), 121.8 (CH, C-3),
122.0 (CH, C-5), 122.6 (CH, C-13), 122.8 (CH, C-14), 127.8 (C,
C-9), 128.5 (C, C-6), 144.7 (CH, C-12), 145.2 (C, C-4), 151.0 (C,
C-11), 151.8 (C, C-1), 165.30 (C@O, C-8), 168.4, 169.1, 169.2,
169.5, 170.0, 170.4 (6 ꢁ C@O, Ac). Anal. Calcd for C33H36O17: C,
56.25; H, 5.15. Found: C, 56.12; H, 5.34.
The compound 9 was obtained from 3,4-diacetoxy cinnamoyl
chloride and glycoside 4. Yield 85%, mp 131–132 °C. UV kmax
(EtOH)/nm: 280. IR (KBr,
m
max/cmꢀ1): 1750, 1640, 1500, 1370,
1210, 1030, 905. 1H NMR (CDCl3, 300 MHz) d: 2.02, 2.03, 2.06,
2.10, 2.27, 2.28, 2.29 (s, 7 ꢁ 3H, Ac), 3.82 (m, 1H, H-50), 4.15 (dd,
1H, J = 9.9, 1.7 Hz, H-60a), 4.24 (dd, 1H, J = 5.3, 12.0 Hz, H-60b),
5.02 (m, 1H, H-10), 5.12 (m, 1H, H-40), 5.17 (m, 2H, H-7), 5.27 (m,
2H, H-20, H-30), 6.39 (d, 1H, J = 15.9 Hz, H-9), 6.97 (dd, 1H, J = 2.5,
8.7 Hz, H-3), 7.09 (d, 1H, J = 7.2 Hz, H-2), 7.10 (s, 1H, H-5), 7.19
(d, 1H, J = 8.4 Hz, H-15), 7.36 (s, 1H, H-12), 7.38 (d, 1H, J = 8.4 Hz,
H-16), 7.62 (d, 1H, J = 16.2 Hz, H-10). 13C NMR (CDCl3, 75.5 MHz)
d: 20.6 (6 ꢁ CH3, Ac), 21.0 (CH3, Ac), 60.6 (CH2, C-7), 61.8 (CH2, C-
60), 68.1 (CH, C-40), 70.9 (CH, C-20), 72.0 (CH, C-30), 72.5 (CH, C-
50), 99.7 (CH, C-10), 117.1 (CH@CH, C-9), 118.7 (CH, C-2), 122.1
(2 ꢁ CH, C-3,C-5), 122.7 (CH, C-15), 123.9 (CH, C-12), 126.5 (CH,
C-16), 127.8 (C, C-6), 133.1 (C, C-11), 142.4 (C, C-13), 143.4 (C, C-
14), 145.5 (CH@CH, C-10), 146.3 (C, C-4), 151.8 (C, C-1), 166.0
(C@O, C-8), 168.0, 169.3, 169.6, 170.2, 170.5 (7 ꢁ C, Ac). HRESIMS
Calcd for [M+Na]+ 781.19504. Found [M+Na]+ 781.19502.
3.5.7. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-5-
acetoxy benzyl (3-methoxy-4-acetoxy) cinnamoate (13)
The compound 13 was obtained from 3-metoxy-4-acetoxy cin-
namoyl chloride and glycoside 4. Yield 60%, mp 157–158 °C. UV
kmax (EtOH)/nm: 323, 304. IR (KBr, m
max/cmꢀ1): 3970, 1760, 1640,
1605, 1380, 1220, 1190, 1175, 180, 1045, 980, 908, 850, 825, 600.
1H NMR (CDCl3, 300 MHz) d: 2.02, 2.03, 2.06, 2.10, 2.27, 2.30 (s,
6 ꢁ 3H, Ac), 3.84 (m, 1H, H-50), 3.84 (s, 3H, OCH3), 4.15 (dd, 1H,
J = 10.2, 1.7 Hz, H-60a), 4.24 (dd, 1H, J = 5.1, 12.3 Hz, H-60b), 5.02
(d, 1H, J = 7.2 Hz, H-10), 5.12–5.34 (m, 5H, H-20, H-30, H-40, H-7),
6.39 (d, 1H, J = 16.2 Hz, H-9), 6.97–7.05 (m, 2H, H-2, H-15), 7.09
(m, 4H, H-3, H-5, H-12, H-16), 7.64 (d, 1H, J = 15.9 Hz, H-10). 13C
NMR (CDCl3, 75.5 MHz) d: 20.6 (5 ꢁ CH3, Ac), 21.0 (CH3, Ac), 55.8
(CH3, OCH3), 60.5 (CH2, C-7), 61.8 (CH2, C-60), 68.1 (CH, C-40),
70.9 (CH, C-20), 72.0 (CH, C-30), 72.5 (CH, C-50), 99.7 (CH, C-10),
111.2 (CH, C-12), 117.1 (CH@CH, C-9), 117.7 (CH, C-2), 121.3 (CH,
C-16), 122.1 (2 ꢁ CH, C-3,C-5), 123.1 (CH, C-15), 127.8 (C, C-6),
133.1 (C, C-11), 141.4 (C, C-14), 144.6 (CH@CH, C-10), 146.2 (C,
C-4), 151.3 (C, C-1), 151.8 (C, C-13), 166.2 (C@O, C-8), 168.6,
169.3, 169.5, 170.1 (6 ꢁ C, Ac). HRESIMS Calcd for [M+Na]+
753.20012, Found [M+Na]+ 753.20007.
3.5.4. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-5-
acetoxy benzylcinnamoate (10)
The compound 10 was obtained from cinnamoyl chloride and
glycoside 4. Yield 40%, mp 74–76 °C. UV kmax (EtOH)/nm: 278. IR
(KBr, m
max/cmꢀ1): 1750, 1640, 1500, 1370, 1210, 1190, 1030, 905.
1H NMR (CDCl3, 300 MHz) d: 2.035, 2.04, 2.07, 2.12, 2.28 (s,
5 ꢁ 3H, Ac), 3.84 (m, 1H , H-50), 4.16 (dd, 1H, J = 2.4, 12.3 Hz, H-
60b), 4.25 (dd, 1H, J = 5.4, 12.3 Hz, H-60a), 5.01 (d, 1H, J = 7.2, Hz,
H-10), 5.15–5.21 (m, 2H, H-40, H-30), 5.25 (m, 1H, H-20), 5.29 (m,
2H, CH2, H-7), 6.45 (d, 1H, J = 15.9 Hz, H-9), 6.99 (dd, 1H, J = 2.7,
8.7 Hz, H-3), 7.10 (s, 1H, H-5), 7.13 (m, 1H, H-2), 7.37 (m, 3H, H-
13, H-14, H-15), 7.52 (m, 2H, H-12,H-16), 7.70 (d, 1H, J = 16.2 Hz,
H-10). 13C NMR (CDCl3, 75.5 MHz) d: 20.4, 20.9 (5 ꢁ CH3, Ac),
60.3 (CH2, C60), 61.6 (CH2, C-7), 68.0 (CH, C-40), 70.7 (CH, C-20),
71.8 (CH, C-30), 72.4 (CH, C-50), 99.6 (CH, C-10), 117.0 (CH, C-2),
117.4 (CH, H-9), 121.9 (2 ꢁ CH, C-3, C-5), 127.7 (C, C-6), 127.9
(2 ꢁ CH, C-12, C-16), 128.7 (2 ꢁ CH, C-13, C-15), 130.2 (CH,C-14),
134.0 (CH, C-11), 145.1 (C, C-4), 146.1 (CH, C-10), 151.6 (CH, C-
1), 166.2 (C@O, C-8), 169.1, 169.3, 169.9, 170.3 (5 ꢁ C@O, Ac). Anal.
Calcd for C32H34O14: C, 59.81; H, 5.33. Found: C, 59.76; H, 5.47.
3.5.8. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-5-
benzoyloxy benzylbenzoate (14)
The compound 14 was obtained from benzoyl chloride and gly-
coside 5. Yield 77%, mp 134–135 °C. UV kmax (EtOH)/nm: 230, 276,

E. V. Stepanova et al. / Carbohydrate Research 388 (2014) 105–111
109
IR (KBr,
m
max/cmꢀ1): 2940, 1720, 1505, 1500, 1380, 1260, 1250,
C-14), 134.9 (C, C-11), 144.5 (CH, C-10), 155.0 (C, C-1), 166.0
(C@O, C-8). Anal. Calcd for C22H24O8: C, 63.45; H, 5.81. Found: C,
63.37; H, 5.95.
1195, 1080, 1060, 1000, 915, 900, 810, 700. 1H NMR (CDCl3,
300 MHz) d: 2.04, 2.05, 2.08, 2.09 (s, 4 ꢁ 3H, Ac), 3,84 (m, 1H, H-
50), 4.17 (d, 1H, J = 10.8, Hz, H-60a), 4.27 (dd, 1H, J = 5.1, 12.0, Hz,
H-60b), 5.09 (d, 1H, J = 7.2, Hz, H-10), 5.16 (m, 1H, H-40), 5.28–5.45
(m, 4H, H-20, H-30, H-7), 7.12–7.21 (m, 2H, H-3, H-5), 7.29 (m,
1H, H-2), 7.41–7.58 (m, 5H, H-11, H-12, H-13, H-18, H-20), 7.60–
7.65 (m, 1H, H-19), 8.06 (d, 2H, J = 7.5 Hz, H-10,H-14), 8.16 (d,
2H, J = 7.8, Hz, H-17, H-21). 13C NMR (DMSO-d6, 75 MHz) d: 20.5
(4 ꢁ CH3, Ac), 60.9 (CH2, C-60), 61.8 (CH2, C-7), 68.2 (CH, C-40),
70.9 (CH, C-20), 72.1 (CH, C-30), 72.6 (CH, C-50), 99.9 (CH, C-10),
117.4 (CH, C-2), 122.0 (CH, C-5), 122.3 (CH, C-3), 128.1 (C, C, C-
6), 128.4 (2 ꢁ CH, C-11, C-13), 128.6 (2 ꢁ CH, C-18, C-20), 129.2
(CH, C-9), 129.7 (2 ꢁ CH, C-17, C-21), 129,9 (CH, C-10), 130.1
(2 ꢁ CH, C-14, C-16), 133.1 (CH, C-12), 133.7 (C, C-19), 146.6 (C,
C-4), 151.9 (C, C-1), 165.2 (C@O, C-15), 166.0 (C@O, C-8), 169.3,
170.1, 170,5 (4 ꢁ C@O, Ac). Anal. Calcd for C35H34O14: C, 61.94;
H, 5.05. Found: C, 61.75; H, 5.13.
3.6.3. 2-(b-D-Glucopyranosyloxy)-benzyl (4-hydroxy) benzoate
(17)
Crystallization from water gave colorless crystals, yield 80%, mp
165–170 °C. UV kmax (EtOH)/nm: 259. IR (KBr,
m
max/cmꢀ1): 3420,
1700, 1610, 1460, 1380, 1280, 1240, 1100, 770, 750. 1H NMR
(DMSO-d6, 300 MHz) d: 3.18 (m, 1H, H-40), 3.27–3.48 (DMSO) (m,
4H, H-20, H-30, H-50, H-60a), 3.68 (m, 1H, H-60b), 4.86 (m, 1H, H-
10), 5.35 (m, 2H, H-7), 6.84 (d, 2H, J = 8.4 Hz, H-11, H-13), 7.01 (t,
1H, J = 7.2 Hz, H-4), 7.16 (d, 1H, J = 8.1 Hz, H-2), 7.28 (m, 1H, H-
3), 7.35 (d, 1H, J = 7.5 Hz, H-5), 7.85 (d, 2H, J = 8.1 Hz, H-10, H-
13
14). C NMR (DMSO-d6, 75.5 MHz) d: 60.7 (CH2, C60), 61.0 (CH2,
C-7), 69.7 (CH, C-40), 73.4 (CH, C-20), 76.5 (CH, C-30), 77.1 (CH, C-
50), 101.0 (CH, C-10), 115.0 (2 ꢁ CH, C-11, C-13), 121.7 (CH, C-2),
120.3 (C, C-9), 121.9 (CH, C-4), 125.4 (C, C-6), 128.3 (CH, C-3),
129.1 (CH, C-5), 131.6 (2 ꢁ CH, C-10, C-14), 155.0 (C, C-1), 162.0
(C, C-12), 166.5 (C@O, C-8). Anal. Calcd for C20H22O9: C, 59.11; H,
5.46. Found: C, 58.95; H, 5.54.
3.6. Selective acetyl group cleavage. General method
To glycoside (3–12) (0.15 mmol) in a mixture of 96%-ethanol
and CHCl3 in proportion 1.5–0.5 mL was added 0.5 mL 36% HCl.
The reaction mixture was stirred and then kept at 30 °C tempera-
ture for 8–13 h. After appropriate time (HPLC control), all solvents
were evaporated at low temperature using vacuum and residue
was subjected to column chromatography applying gradient elu-
tion with chloroform and chloroform–ethanol mixture (from ratio
15:1 to 4:1). Analytical samples were purified by recrystallization
from ethanol or water.
3.6.4. 2-(b-D-Glucopyranosyloxy)-benzyl 3-methoxy (4-hydroxy)
benzoate (18)
Crystallization from water afforded colorless crystals, yield 35%,
mp 173–177 °C. UV kmax (EtOH)/nm: 265, 292. IR (KBr, m
max/cmꢀ1):
3470, 3380, 2930, 1700, 1690, 1610, 1510, 1300, 1230, 1090, 760,
1
750. H NMR (DMSO-d6, 300 MHz) d: 3.16 (m, 1H, H-40), 3.27–
3.38 (DMSO) (m, 2H, H-20, H-30), 3.43 (m, 2H, H- 50, H-60a), 3.68
(d, 1H, J-11.4 Hz, H-60b), 3.82 (s, 3H, OCH3), 4.86 (m, 1H, H-10),
5.37 (m, 2H, CH2, H-7), 6.86 (d, 1H, J = 8.1 Hz, H-13), 7.01 (t, 1H,
J = 7.5 Hz, H-4), 7.16 (d, 1H, J = 8.1 Hz, H-2), 7.29 (m, 1H, H-3),
7.34 (d, 1H, J = 7.5 Hz, H-5), 7.48 (s, 1H, H-10), 7.51 (dd, 1H,
J = 1.5, 8.4 Hz, H-14). 13C NMR (DMSO-d6, 75.5 MHz) d: 55.7
(OCH3), 60.8 (CH2, C60), 61.1 (CH2, C-7), 69.7 (CH, C-40), 73.3 (CH,
C-20), 76.5 (CH, C-30), 77.2 (CH, C-50), 101.0 (CH, C-10), 112.5 (CH,
C-10), 115.0 (CH, C-13), 115.1 (CH, C-2), 120.5 (C, C-9), 121.9
(CH, C-4), 123.5 (CH, C-14), 125.2 (CH, C-6), 129.4 (C, C-5), 130.3
(CH, C-3), 145.4 (C, C-11), 151.5 (C, C-12), 155.2 (C, C-1), 165.4
(C@O, C-8). Anal. Calcd for C21H24O10: C, 57.80; H, 5.54. Found: C,
57.71; H, 5.70.
3.6.1. 2-(b-D-Glucopyranosyloxy)-benzyl (3,4-dihydroxy)
cinnamoate (populoside) (15)
Crystallization from acetone gave pale yellow crystals, yield
50%, mp 178–179 °C, lit.22 186–188 °C, lit.7 169–170 °C, lit.6,17
168–169 °C. UV kmax (EtOH)/nm: 311. IR (KBr, m
max/cmꢀ1): 3450,
2920, 1680, 1600, 1370, 1280, 1160, 1090, 1050, 910, 760. 1H
NMR (DMSO-d6, 300 MHz) d: 3.17 (m, 1H, H-40), 3.26–3.47 (DMSO)
(m, 3H, H-20, H-30, H-50), 4.48 (m, 1H, H-60b), 3.68 (d, 1H,
J = 11.4 Hz, H-60a), 4.84 (m, 1H, H-10), 5.22 (m, 2H, H-7), 6.32 (d,
1H, J = 15.9 Hz, H-9), 6.75 (d, 1H, J = 8.1 Hz, H-15), 7.00 (m, 3H,
H-2, H-4, H-12), 7.14 (d, 1H, J = 7.8 Hz, H-16), 7.28 (m, 2H, H-3,
H-5), 7.50 (d, 1H, J = 15.9 Hz, H-10). 13C NMR (DMSO-d6,
75.5 MHz) d: 60.9 (2 ꢁ CH2, C60, C-7), 69.8 (CH, C-40), 73.2 (CH,
C-20), 76.5 (CH, C-30), 77.1 (CH, C-50), 101.1 (CH, C-10), 114.0 (CH,
C-12), 114.9 (CH, C-2), 115.0 (CH, C-9), 115.9 (CH, C-15), 121.5
(CH, C-4), 122.0 (CH, C-16), 125.1 (CH, C-6), 125.7 (CH,C-11),
128.2 (CH, C-3), 129.0 (CH, C-5), 145.5 (2 ꢁ C, C-10, C-13), 148.2
(C, C-14), 155.1 (C, C-1), 166.4 (C@O, C-8). The data are in agree-
ment with literature.6,7
3.6.5. 2-(b-D-Glucopyranosyloxy)-5-hydroxy benzyl (3,4-
dihydroxy) cinnamoate (19)
Crystallization from acetone gave yellowish crystals, yield 30%,
mp 156–158 °C, lit.6 157–158 °C. UV kmax (EtOH)/nm: 248, 300,
331. IR (KBr,
m
max/cmꢀ1): 3272, 1680, 1610, 1560, 1520, 1460,
1380, 1280, 1210, 1080, 1050, 990, 810. 1H NMR (DMSO-d6,
300 MHz) d: 3.17 (m, 1H, H-40), 3.26–3.47 (DMSO) (m, 4H, H-20,
H-30, H-50, H-60), 3.66 (m, 1H, H-60), 4.62 (d, 1H, J = 6.0 Hz, H-10),
5.22 (m, 2H, H-7), 6.31 (d, 1H, J = 16.2 Hz, H-9), 6.63 (dd, 1H,
J = 9.0, 1.5 Hz, H-3), 6.70 (d, 1H, J = 2.7 Hz, H-5), 6.73 (d, 1H,
J = 8.1 Hz, H-15), 7.00–7.03 (m, 2H, H-12, H-16), 7.06 (m, 1H, H-
2), 7.50 (d, 1H, J = 15.6 Hz, H-10). 13C NMR (DMSO-d6, 75.5 MHz)
d: 60.8 (CH2, C-7), 61.0 (CH2, C-60), 69.8 (CH, C-40), 73.4 (CH,
C-20), 76.5 (CH, C-30), 77.1 (CH, C-50), 102.8 (CH, C-10), 113.8 (CH,
C-12), 114.0 (CH@CH, C-9), 114.9 (CH, C-3), 115.2 (CH, C-5),
115.9 (CH, C-15), 117.7 (CH, C-2), 121.7 (CH, C-16), 126.5 (CH,
C-11), 127.1 (C, C-6), 145.6 (C, C-1, CH@CH, C-10,), 147.9 (CH, C-
13), 148.8 (C, C-14), 152.8 (C, C-4), 166.5 (C@O, C-8). The data agree
well with those given in Ref. 6.
3.6.2. 2-(b-
Crystallization from water gave colorless crystals, yield 40%, mp
110–112 °C. UV kmax (EtOH)/nm: 278. IR (KBr,
max/cmꢀ1): 3380,
D-Glucopyranosyloxy)-benzylcinnamoate (16)
m
2920, 1700, 1640, 1500, 1240, 1080, 1050, 770, 750. 1H NMR
(DMSO-d6, 300 MHz) d: 3.17 (m, 1H, H-40), 3.26–3.36 (m, 2H, H-
20, H-30), 3.43–3.50 (m, 2H, H-60b, H-50), 3.69 (d, 1H, J = 10.8 Hz,
H-60a), 4.83 (m, 1H, H-10), 5.30 (m, 2H, H-7), 6.69 (d, 1H,
J = 16.2 Hz, H-9), 7.01 (t, 1H, J = 7.5 Hz, H-4), 7.16 (d, 1H,
J = 7.8 Hz, H-2), 7.29 (d, 1H, J = 7.2 Hz, H-5), 7.36 (m, 1H, H-3),
7.42 (m, 3H, H-13, H-14, H-15), 7.68 (d, 1H, J = 16.2 Hz, H-10),
7.74 (m, 2H, H-12, H-16). 13C NMR (DMSO-d6, 75.5 MHz) d: 60.5
(CH2, C60), 60.9 (CH2, C-7), 69.5 (CH, C-40), 73.0 (CH, C-20), 76.3
(CH, C-30), 76.9 (CH, C-50), 100.9 (CH, C-10), 114.8 (CH, C-2), 117.8
(CH, H-9), 121.7 (CH, C-4), 124.9 (C, C-6), 128.3 (2 ꢁ CH, C-12,
C-16), 128.8 (3 ꢁ CH, C-3, C-13, C-15), 129.2 (CH,C-5), 130.5 (CH,
3.6.6. 2-(b-D-Glucopyranosyloxy)-5-hydroxy benzylcinnamoate
(20)
Crystallization from water gave colorless crystals, yield 34%, mp
135–139 °C. UV kmax (EtOH)/nm: 282. IR (KBr,
m
max/cmꢀ1): 3425,

110
E. V. Stepanova et al. / Carbohydrate Research 388 (2014) 105–111
2920, 1700, 1635, 1500, 1210, 1080, 770. 1H NMR (DMSO-d6,
300 MHz) d: 3.23 (m, 1H, H-40), 3.30–3.48 (DMSO) (m, 4H, H-20,
H-30, H-50, H-60a), 3.68 (m, 1H, H-60b), 4.62 (d, 1H, J = 6.3, Hz, H-
10), 5.26 (m, 2H, CH2, H-7), 6.62–6.75 (m, 3H, H-3, H-5, H-9), 7.00
(d, 1H, J = 9.0 Hz, H-2), 7.43 (m, 3H, H-13, H-14, H-15), 7.68 (d,
1H, J = 16.2 Hz, H-10), 7.74 (m, 2H, H-12, H-16). 13C NMR
(DMSO-d6, 75.5 MHz) d: 60.7 (CH2, C60), 60.9 (CH2, C-7), 69.8 (CH,
C-40), 73.2 (CH, C-20), 76.4 (CH, C-30), 77.0 (CH, C-50), 102.6
(CH, C-10), 114.8 (CH, C-3), 115.3 (CH, C-5), 117.4 (CH, C-2), 118.0
(CH, H-9), 126.7 (C, C-6), 128.3 (2 ꢁ CH, C-12, C-16), 128.9
(2 ꢁ CH, C-13, C-15), 130.5 (CH,C-14), 134.0 (CH, C-11), 144.7 (C,
C-1), 147.9 (CH, C-10), 152.1 (CH, C-4), 166.0 (C@O, C-8). Anal.
Calcd for C22H24O9: C, 61.11; H, 5.59. Found: C, 61.00; H, 5.65.
C-9), 118.7 (CH, C-2), 122.1 (2 ꢁ CH, C-3,C-5), 122.7 (CH, C-15),
123.9 (CH, C-12), 126.5 (CH, C-16), 127.8 (C, C-6), 133.1 (C, C-11),
142.4 (C, C-13), 143.4 (C, C-14), 145.5 (CH@CH, C-10), 146.3 (C,
C-1), 151.8 (C, C-4), 166.0 (C@O, C-8). Anal. Calcd for C23H26O11
:
C, 57.74; H, 5.48. Found: C, 57.67; H, 5.53.
3.6.10. 2-(b-
benzylbenzoate (24)
Crystallization from water gave colorless crystals, yield 60%, mp
190–194 °C. UV kmax (EtOH)/nm: 230, 276. IR (KBr,
max/cmꢀ1):
D-Glucopyranosyloxy)-5-benzoyloxy
m
2950, 1730, 1715, 1500, 1390, 1255, 1200, 1080, 1060, 1040, 890,
1
795 703. H NMR (DMSO, 300 MHz) d.: 3,17 (m, 1H, H-40), 3.30–
3.38 (DMSO) (m, 3H, H-20, H-30, H-50), 3.45–3.52 (m, 1H, H-60a),
3.69–3.75 (m, 1H, H-60b), 4.91 (d, 1H, J = 6.6, Hz, H-10), 5.39 (dd,
2H, J = 13.5, 3.6 , Hz, H-7), 7.27 (m, 2H, H-3, H-5), 7.33 (m, 1H,
H-2), 7.50–7.68 (m, 5H, H-11, H-12, H-13, H-18, H-20), 7.72–7.77
(m, 1H, H-19), 8.01 (d, 2H, J = 7.2 Hz, H-10,H-14), 8.11 (d, 2H,
J = 6.9, Hz, H-17, H-21). 13C NMR (DMSO, 75.5 MHz) d: 60.9 (CH2,
C-60), 61.4 (CH2, C-7), 69.8 (CH, C-40), 73.1 (CH, C-20), 76.5 (CH, C-
30), 76.9 (CH, C-50), 100.1 (CH, C-10), 117.4 (CH, C-2), 121.9 (CH,
C-5), 122.8 (CH, C-3), 126.1 (C, C, C-6), 129.0 (5 ꢁ CH, C-9, C-11,
C-13, C-18, C-20), 129.2 (2 ꢁ CH, C-17, C-21), 129,5 (CH, C-10),
129.8 (2 ꢁ CH, C-14, C-16), 133.2 (CH, C-12), 134.0 (C, C-19),
145.0 (C, C-4), 152.9 (C, C-1), 164.9 (C@O, C-15), 165.8 (C@O, C-
8). Anal. Calcd for C27H26O10: C, 63.53; H, 5.13. Found: C, 63.60;
H, 5.25.
3.6.7. 2-(b-D-Glucopyranosyloxy)-5-hydroxy benzyl (4-hydroxy)
benzoate (21)
Crystallization from water gave colorless crystals, yield 55 %,
mp 140 °C. UV kmax (EtOH)/nm: 257. IR (KBr, m
max/cmꢀ1): 3360,
2930, 1680, 1610, 1495, 1280, 1210, 1070, 770. 1H NMR (DMSO-
d6, 300 MHz) d: 3.21 (m, 1H, H-40), 3.30–3.44 (DMSO) (m, 4H, H-
20, H-30, H- 50, H-60a), 3.67 (m, 1H, H-60b), 4.63 (m, 1H, H-10), 5.32
(m, 2H, CH2, H-7), 6.64 (dd, 1H, J = 2.7, 9.3 Hz, H-3), 6.75 (d, 1H,
J = 2.4, Hz, H-5), 6.85 (d, 2H, J = 8.4, Hz, H-11, H-13), 7.00 (d, 1H,
J = 8.7 Hz, H-2), 7.85 (d, 2H, J = 8.4 Hz, H-10, H-14). 13C NMR
(CDCl3, 75.5 MHz) d: 61.8 (CH2, C60), 61.9 (CH2, C-7), 69.8 (CH,
C-40), 74.2 (CH, C-20), 76.5 (CH, C-30), 77.0 (CH, C-50), 102.6 (CH,
C-10), 114.2 (CH, C-5), 115.0 (CH, C-3), 115.5 (2 ꢁ CH, C-11, C-13),
117.8 (CH, C-2), 120.2 (C, C-9), 127.0 (C, C-6), 131.4 (2 ꢁ CH,
C-10, C-14), 147.7 (C, C-1), 152.2 (C, C-4), 163.0 (C, C-12), 165.3
(C@O, C-8). Anal. Calcd for C20H22O10: C, 56.87; H, 5.25. Found: C,
56.80; H, 5.29.
3.7. 4-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyloxy)-
phenylbenzoate (26)
The compound 26 was obtained by glycosylation of (25), yield,
mp 150–151 °C, lit.25 136–138 °C, lit.30 154–155 °C. UV kmax
3.6.8. 2-(b-
D-Glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-
(EtOH)/nm: 283. IR (KBr, m m
max/cmꢀ1): /cm–1: 1740, 1505, 1370
4-hydroxy) benzoate (22)
Crystallization from water gave colorless crystals, yield 36 %,
mp 128–136 °C. UV kmax (EtOH)/nm: 264, 292. IR (KBr, mmax
1230, 1200, 1065, 700. 1H NMR (CDCl3, 300 MHz) d.: 2.04, 2.05,
2.08 (s, 4 ꢁ 3H, Ac), 3.85 (m, 1H, H-50), 4.15 (d, 1H, J = 12.3 Hz, H-
60b), 4.27 (dd, 1H, J = 5.4, 12.3 Hz, H-60a), 5.05 (d, 1H, J = 6.9 Hz,
H-10), 5.15 (m, 1H, H-40), 5.25–5.34 (m, 2H, H-20, H-30), 7.03 (d,
2H, J = 9.0 Hz, H-2, H-6), 7.13 (d, 2H, J = 9.0 Hz, H-3, H-5), 7.48
(m, 2H, H-18, H-20), 7.61 (t, 1H, J = 7.2 Hz, H-19), 8.17 (d, 2H,
J = 7.5 Hz, H-17, H-21). 13C NMR (CDCl3, 75.5 MHz) d: 20.7
(4 ꢁ CH3, COCH3), 62.1 (CH2, C60), 68.4 (CH, C-40), 71.3 (CH, C-20),
72.2 (CH, C-50), 72.8 (CH, C-30), 99.7 (CH, C-10), 118.2 (2 ꢁ CH, C-
2, C-6), 122.8 (2 ꢁ CH, C-5, C-3), 128.7 (2 ꢁ CH, C-18, C-20),
129.5 (C, C-16), 130.3 (2 ꢁ CH, C-17,C-21), 133.8 (CH, C-19),
146.6 (C, C-4), 154.7 (C, C-1), 165.0 (C@O, C-15), 169.5, 170.3,
170.7 (4 ꢁ C, Ac). The data are in agreement with literature.25
/
cmꢀ1): 2970, 1695, 1520, 1290, 1215, 1080, 1240, 990, 760. 1H
NMR (DMSO-d6, 300 MHz) d: 3.17 (m, 1H, H-40), 3.22–3.44 (m,
4H, H-20, H-30, H-50, H-60a), 3.67 (d, 1H, J-11.4 Hz, H-60b), 3.82 (s,
3H, OCH3), 4.63 (m, 1H, H-10), 5.33 (m, 2H, CH2, H-7), 6.63 (dd,
1H, J = 2.7, 8.7 Hz, H-3), 6.74 (d, 1H, J = 3.0 Hz, H-5), 6.87 (d, 1H,
J = 8.1 Hz, H-13), 7.00 (d, 1H, J = 8.7 Hz, H-2), 7.49 (s, 1H, H-10),
7.54 (dd, 1H, J = 3.0, 8.4 Hz, H-14). 13C NMR (DMSO-d6, 75.5 MHz)
d: 55.8 (OCH3), 60.9 (CH2, C60), 61.0 (CH2, C-7), 69.8 (CH, C-40),
73.4 (CH, C-20), 76.6 (CH, C-30), 77.1 (CH, C-50), 102.6 (CH, C-10),
112.7 (CH, C-10), 114.2 (CH, C-13), 115.0 (CH, C-5), 115.3 (CH,
C-3), 117.7 (CH, C-2), 120.5 (C, C-9), 123.6 (CH, C-14), 127.1 (C,
C-6), 147.3 (CH, C-11), 147.8 (C, C-1), 151.7 (C, C-12), 152.4 (C,
C-4), 165.5 (C@O, C-8). Anal. Calcd for C21H24O11: C, 55.75; H,
5.35. Found: C, 55.71; H, 5.37.
3.8. 4-(b-D-Glucopyrfmanosyloxy)-phenylbenzoate (27)
The compound 27 was obtained according to procedure for 14–
23 from glycoside 25 and was crystallized from water. Yeild 36%,
3.6.9. 2-(b-
4-hydroxy) cinnamoate (23)
D
-Glucopyranosyloxy)-5-hydroxy benzyl (3-methoxy-
mp 189–196 °C. UV kmax (EtOH)/nm: 230, 269. IR (KBr, mmax
/
cmꢀ1): /cmꢀ1: 3540, 3390, 2890, 1712, 1600, 1510, 1455, 1400,
m
Crystallization from water gave colorless crystals, yield 48%, mp
99–100 °C. UV kmax (EtOH)/nm: 296, 325. IR (KBr,
1275, 1240, 1200, 1080, 1040, 820, 710. 1H NMR (DMSO,
300 MHz) d: 3.17–3.21 (m, 1H, H-40), 3.25–3.35 (m, 3H, H-20, H-3,
H-50), 3.44–3.53 (1H, m, H-60a), 3.69 (dd, 1H, J = 4.5, 11.1, Hz, H-
60b), 4.87 (d, 1H, J = 6.9, Hz, H-10), 7.09 (d, 2H, J = 8.7 Hz, H-2, H-
6), 7.19 (d, 2H, J = 8.7 Hz, H-3, H-5), 7.58 (m, 2H, H-10, H-12),
7.72 (t, 1H, J = 7.2 Hz, H-11), 8.11 (d, 2H, J = 7.8 Hz, H-9, H-13).
13C NMR (DMSO, 75.5 MHz) d: 60.6 (CH2, C60), 69.6 (CH, C-40),
73.2 (CH, C-20), 76.5 (CH, C-50), 77.0 (CH, C-30), 100.6 (CH, C-10),
116.9 (2 ꢁ CH, C-2, C-6), 122.6 (2 ꢁ CH, C-5, C-3), 129.0 (2 ꢁ CH,
C-16, C-18, C-20), 129.7 (2 ꢁ CH, C-17,C-21), 134.0 (CH, C-19),
144.8 (C, C-4), 155.1 (C, C-1), 165.0 (C@O, C-8). 164.8. Anal. Calcd
for C19H20O8: C, 60.63; H, 5.36. Found: C, 60.50; H, 5.52.
m
max/cmꢀ1):
3405, 2930, 1690, 1600, 1500, 1270, 1210, 1175, 1075, 1035,
1
810. H NMR (MeOD, 300 MHz) d.: 3.82 (m, 1H, H-50), 4.15 (dd,
1H, J = 9.9, 1.7 Hz, H-60a), 4.24 (dd, 1H, J = 5.3, 12.0 Hz, H-60b),
5.02 (m, 1H, H-10), 5.12 (m, 1H, H-40), 5.17 (m, 2H, H-7), 5.27 (m,
2H, H-20, H-30), 6.39 (d, 1H, J = 15.9 Hz, H-9), 6.97 (dd, 1H, J = 2.5,
8.7 Hz, H-3), 7.09 (d, 1H, J = 7.2 Hz, H-2), 7.10 (s, 1H, H-5), 7.19
(d, 1H, J = 8.4 Hz, H-15), 7.36 (s, 1H, H-12), 7.38 (d, 1H, J = 8.4 Hz,
H-16), 7.62 (d, 1H, J = 16.2 Hz, H-10). 13C NMR (MeOD, 75.5 MHz)
d: 60.6 (CH2, C-7), 61.8 (CH2, C-60), 68.1 (CH, C-40), 70.9 (CH, C-
20), 72.0 (CH, C-30), 72.5 (CH, C-50), 99.7 (CH, C-10), 117.1 (CH@CH,

E. V. Stepanova et al. / Carbohydrate Research 388 (2014) 105–111
10. Gülçin, I. Toxicology 2006, 217, 213–220.
111
Acknowledgements
11. Pérez-Alvarez1, V.; Fernández-Martinez, E.; Morales-Ríos, M. S.; Bobadilla, R.
A.; Muriel, P. Proc. West. Pharmacol. Soc. 2003, 46, 136–138.
12. Lodovici, M.; Guglielmi, F.; Meoni, M.; Dolara, P. Food Chem. Toxicol. 2001, 39,
1205–1210.
13. Ou, Sh.; Kwok, K. Ch. J. Sci. Food Agric. 2004, 84, 1261–1269.
14. Chong, K. P.; Rossall, S.; Atong, M. J. Agric. Sci. 2009, 1, 15–20.
15. Khadem, Sh.; Marles, R. J. Molecules 2010, 15, 7985–8005.
16. Itoh, A.; Isoda, K.; Kondoh, M.; Kawase, M.; Watari, A.; Kobayashi, M., et al Biol.
Pharm. Bull. 2010, 33, 983–987.
17. Kumar, S.; Prahalathan, P.; Raja, B. Redox Rep. 2011, 16, 208–215.
18. Prince, P. S. M.; Rajakumar, S.; Dhanasekar, K. Eur. J. Pharmacol. 2011, 668, 233–
240.
19. Belyanin, M. L.; Stepanova, E. V.; Ogorodnikov, V. D. Carbohydr. Res. 2012, 363,
66–72.
20. Briggs, J. C.; Haines, A. H.; Taylor, R. J. K. J. Chem. Soc., Chem. Commun. 1992,
1039–1041.
21. Zemplen, G.; Bognar, R.; Pongor, G. Acta Chim. Hung. Tomus. 1959, 19, 285–
293.
22. Erickson, R. L.; Pearl, I. A.; Darling, S. F. Phytochemistry 1970, 9, 857–863.
23. Lee, Y. S.; Cui, Ch. B.; Kim, J. K.; Bae, Y. S.; Lee, J. Y.; Kang, I. J., et al Korean Soc
Appl. Biol. Chem. 2010, 53, 729–733.
24. Choudhary, M. I.; Fatima, N.; Abbasi, M. A.; Jalil, S.; Ahmad, V. U.; Rahman, A.
Bioorg. Med. Chem. 2004, 12, 5793–5798.
This work was supported by the scientific program ‘Nauka’ No.
2387. We would like to thank the Department of Chemical Analysis
of Tomsk State University for assistance in obtaining elemental
analysis data.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.carres.2014.02.
014.
References
1. Hedner, T.; Everts, B. Clin. Rheumatol. 1998, 17, 17–25.
2. Boeckler, G. A.; Gershenzon, J.; Unsicker, S. B. Phytochemistry 2011, 72, 1497–
1509.
3. Chen, P. D. Chin. Tradit. Herb. Drugs 2006, 37, 1607–1608.
4. Choudhary, M. I.; Fatima, N.; Abbasi, M. A.; Jalil, S.; Ahmad, V. U.; Atta-ur-
Rahman Bioorg. Med. Chem. 2004, 12, 5793–5798.
5. Lee, K. H.; Yang, M. C.; Kim, K. H.; Kwon, H. C.; Choi, S. U.; Lee, K. R. Molecules
2008, 13, 41–45.
6. Si, Ch. L.; Li, Sh. M.; Liu, Z.; Kim, J. K.; Bae, Y. S. Nat. Prod. Res. 2011, 25, 1396–
1401.
7. Zhang, X. F.; Thuong, P. T.; Min, B. S. J. Nat. Prod. 2006, 69, 1370.
8. Poblocka-Olech, L.; Krauze-Baranowska, M.; Glod, D.; Kawiak, A.; Lojkowska, E.
Phytochem. Anal. 2010, 21, 463–469.
25. Lee, Y. S. U.S. Patent 6,388,103 B2, 2002.
26. Seo, D. H.; Jung, J. H.; Lee, J. E.; Jeon, E. J.; Kim, W.; Park, C. S. Appl. Microbiol.
Biotechnol. 2012, 95, 1417–1425.
27. Varma, M.; Varma, R. S.; Parthasarathy, M. R. Monatsh. Chem. 1980, 111. 469-
47.
28. Perold, G. W.; Rosenberg, M. E. K.; Howard, A. S.; Huddle, P. A. J. Chem. Soc.,
Perkin Trans. 1 1979, 239–243.
29. Yang, R. L.; Li, N.; Ye, M.; Zong, M. H. J. Mol. Catal. B Enzym. 2010, 67, 41–44.
30. Robertson, A.; Waters, R. B. J. Chem. Soc. 1930, 2729–2733.
9. Lim, E.; Doucet, C. J.; Li, Y.; Elias, L.; Worrall, D.; Spencer, S. P., et al J. Biol. Chem.
2002, 277, 586–592.