Synthesis of hydroxyethyl starch derivatives with phenylpropanoid fragments attached through ester or sulfide bonds

Article abstract of DOI:10.1007/s11172-014-0710-8

Approaches to the synthesis of hydroxyethyl starch derivatives containing phenylpropanoic acid fragments with various degree of substitution were suggested. Esterification of hydroxyethyl starch in heterogeneous aqueous organic medium gave rise to the cor

Full text of DOI:10.1007/s11172-014-0710-8

Russian Chemical Bulletin, International Edition, Vol. 63, No. 9, pp. 2130—2135, September, 2014
2130
Synthesis of hydroxyethyl starch derivatives with phenylpropanoid fragments
attached through ester or sulfide bonds*
M. A. Torlopov, E. V. Udoratina, and V. Yu. Belyaev
Institute of Chemistry, Komi Scientific Center of the Ural Branch of the Russian Academy of Sciences,
48 ul. Pervomaiskaya, 167982 Syktyvkar, Russian Federation.
Fax: +7 (821) 221 8477. Eꢀmail: udoratinaꢀev@chemi.komisc.ru
Approaches to the synthesis of hydroxyethyl starch derivatives containing phenylpropanoic
acid fragments with various degree of substitution were suggested. Esterification of hydroxyꢀ
ethyl starch in heterogeneous aqueous organic medium gave rise to the corresponding esters of
ferulic, pꢀcoumaric, and sinapinic acids. A reaction of hydroxyethyl starch mercaptodeoxy
derivative with acetoxy derivatives of these hydroxycinnamic acids led to the mixed polyꢀ
saccharides with the oxyphenylꢀ3ꢀmercaptopropanoic acid fragments.
Key words: phenylpropanoids, hydroxyethyl starch, ferulic acid, bromodeoxypolysacchaꢀ
rides, mercaptodeoxypolysaccharides.
Phenylpropanoids are a large class of plant compounds
composed of structural fragments of cinnamic acid and its
derivatives, as well as of their esters and glycosides. These
compounds like other phenylpropanoids possess high bioꢀ
logical activity and are of interest as a starting material for
the synthesis of new molecules with predicted antioxiꢀ
dant, antiviral, and adaptogenic properties.1
One of the main approaches to the design of new comꢀ
pounds using phenylpropanoids is their combination with
carbohydrate components: monoꢀ, oligoꢀ, and polysacꢀ
charides. Such an approach to a certain extent is a copying
organization of many macromolecular natural structures
including phenylpropanoids.
There are known examples when polysaccharides are
used for the synthesis of macromolecular compounds conꢀ
taining phenylpropanoic fragments. Earlier, chitosan, inꢀ
ulin, and xylan derivatives esterified with hydroxycinnamꢀ
ic acids were obtained.2—4 Such compounds exhibit antiꢀ
oxidant properties, therefore, it seems very promising to
study synthesis of compounds of polysaccharides and pheꢀ
nylpropanoids which include sulfurꢀcontaining groups in
lower oxidation states. For the synthesis of such comꢀ
pounds, one can use the reaction of thiols with ,ꢀunsatꢀ
urated acids, which proceeds similarly to the reaction of
lowꢀmolecularꢀmass thiols and cinnamic acid.5
Results and Discussion
We have chosen acetoxyphenylpropenoic acids as comꢀ
pounds from the family of phenylpropanoids for the atꢀ
tachment to 2ꢀhydroxyethyl starch (HES, 1) and its merꢀ
captodeoxy derivative.
The synthesis of hydroxyphenylpropenoic esters with
HES (compounds 2—4) was performed in several steps
(Scheme 1). The key step of esterification of polysacchaꢀ
ride with acetoxycinnamoyl chlorides was carried out in
the heterogeneous system water—CHCl3 in the presence
of NaOH with the formation of polysaccharides 2Ac—4Ac.
Acetoxy derivatives of ferulic, pꢀcoumaric, and sinapinic
acids were synthesized according to the method given in
the work;6 the corresponding acetoxyphenylpropenoyl
chlorides were obtained by treatment with SOCl2. In the
last step, the acetate groups at the phenol hydroxy groups
of polysaccharides 2Ac—4Ac were removed by treatment
with CH3COONH4 in a mixture of water—DMAc3 to obꢀ
tain polysaccharide derivatives 2—4 with various degrees
of substitution (DSPh) containing fragments of oxyꢀ
phenylpropenoic acids: ferulic (2), pꢀcoumaric (3), and
sinapinic (4).
Degree of substitution in these derivatives can be conꢀ
trolled by the molar excess of acetoxycinnamoyl chloride
used relative to a polysaccharide monomeric unit. A twoꢀ
fold excess of chlorides gave the samples with DSPh > 1.0.
The molar ratio of acetoxycinnamoyl chloride to a monoꢀ
meric unit of polysaccharide 1 equal to 0.1 : 1.0 resulted in
derivatives with DSPh < 0.10, whereas this ratio equal to
0.5 : 1.0 gave the samples with DSPh = 0.27—0.31 (Table 1).
Derivatives of polysaccharide 1 esterified with acetoxyꢀ
phenylpropenoic acids are well soluble in some polar aproꢀ
In the present work, we suggested an approach to the
synthesis of polysaccharides with oxyphenylpropanoic
fragments attached through ester or sulfide bonds, using
starch derivative as an example.
* Based on the materials of the VIII AllꢀRussian Conference
"Chemistry and Technology of Plant Substances" (October 7—10,
2013, Kaliningrad).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2130—2135, September, 2014.
1066ꢀ5285/14/6309ꢀ2130 © 2014 Springer Science+Business Media, Inc.

Phenylpropanoids derivatives of polysaccharides
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2131
Scheme 1
R1 = H,
(2); H,
(3); H,
(4)
Reagents and conditions: i. 3ꢀ(4ꢀacetoxyphenyl)propꢀ2ꢀenoic chlorides, CHCl3/H2O, NaOH, 25 C, 6 h; ii. deacetylation:
MeCOONH4/DMAc—H2O, 2 h, 25 C.
tic solvents (DMSO, DMF, DMAc), whereas those with
DSPh < 0.15 are also soluble in water. After removal of the
acetyl group from the phenol hydroxyl, polysacchaꢀ
rides 2—4 only with DSPh <0.08 are soluble in water.
To incorporate in the structure of polysaccharide of
hydroxyphenylꢀ3ꢀmercaptopropanoic acid fragments and
to form sulfide bonds, we used a thiolꢀene reaction, in
which the synthesized from bromodeoxyꢀHES (5) HES
mercaptodeoxy derivative (6) served as the thiol compoꢀ
nent. Hydroxyꢀ and acetoxycinnamic acids were used as
,ꢀunsaturated components.
The isolated bromodeoxypolysaccharides 5a—c are
white powders, which are soluble in water when the conꢀ
tent of bromine is <15 wt.%. When a twoꢀfold molar exꢀ
cess of the brominating system was used, the sample was
obtained with DSBr = 1.19, that corresponds to the mass
content of bromine (Br) = 34.5% (see Table 2, comꢀ
pound 5a). The content of bromine in HES can be reguꢀ
lated by the change in the ratio of the brominating agent
to the elementary unit, considering that about oneꢀhalf of
the brominating agent is consumed in the target reaction
(see Table 2).
Polysaccharide 5 (Scheme 2) containing bromodeoxꢀ
yglucose units was synthesized using the triphenylphosꢀ
phine—NBS brominating system (Ph3P—NBS). This sysꢀ
tem was used earlier for the synthesis of 6ꢀbromoꢀ6ꢀ
deoxyamylose, 6ꢀbromoꢀ6ꢀdeoxycellulose and some othꢀ
er bromodeoxypolysaccharides. It acted to selectively subꢀ
stitute a hydroxy group at the primary carbon atom of
polysaccharides with the bromine atom.7,8 Bromodeoxyꢀ
polysaccharides 5a—c with various DSBr were obtained
based on compound 1 (Table 2).
The synthesis of mixed mercaptodeoxypolysaccharide 6
(see Scheme 2) was carried out by the reaction of comꢀ
pound 5 with thiocarbamide and subsequent hydrolysis of
formed thiouronium salts in alkaline medium. Polyꢀ
saccharide 6 even with a low degree of substitution is poorly
soluble in water, but can be dissolved in alkalis or DMF.
The thiolꢀene reaction of polysaccharide 6 and acetꢀ
oxyphenylcarboxylic acids was carried out in DMF at difꢀ
ferent temperatures, as well as in the presence of fluorine
ions. Table 3 shows the results of the thiolꢀene reaction of
polysaccharide 6 with DSSH = 0.52 with ferulic (7a),
acetoxyferulic (7b—e), acetoxycoumaric (8), and acetꢀ
oxysinapinic (9) acids.
Table 1. Synthesis of esters 2—4*: conditions and results
Hydroxyphenylpropenoic acids used as ,ꢀunsaturꢀ
ated components do not give the thiolꢀene reaction with
the thiol groups of polysaccharide 6 (see Table 3, comꢀ
pound 7a). Addition of acetoxyphenylpropenoic acids to
polysaccharide 6 with the formation of sulfide bond reꢀ
quires prolonged heating of the reaction mixture. It was
found that an increase in temperature to 100 C provides
the highest conversion of the thiol groups to the sulfide
ones without significant decrease in the yield of the modiꢀ
Compound
Acid moiety
DSPh
2
3
4
Ferulic
pꢀCoumaric
Sinapinic
0.29
0.31
0.27
* The molar ratio of acetoxyphenolic acyl chloride to
polysaccharide monomeric unit was 0.5 : 1.0.

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Torlopov et al.
Scheme 2
5: R2 = OH, Br; 6: R3 = OH, SH; 7: R4 = OH, SH,
; 8: R4 = OH, SH,
; 9: R4 = OH, SH,
Reagents and conditions: i. DMAc, Ph3P—NBS, 80 C, 4 h; ii. DMF, (NH2)2CS, 80 C, 24 h; NaOH. iii. 1) DMF, 4ꢀacetoxyferulic,
4ꢀacetoxycoumaric, or 4ꢀacetoxysinapinic acid, 100 C, 24 h; 2) 0.5 N NaOH.
fied polysaccharide. Under the selected conditions, the
greater part of phenylpropanoic fragments is incorporated
in the structure of polymer within 24 h (see Table 3, comꢀ
pounds 7c and 7d) with obtaining polysaccharides conꢀ
taining the hydroxyphenylꢀ3ꢀmercaptopropanoic acid
fragments. However, the DSSPh values obtained indicate
that under these conditions only 70% of thiol groups of
compound 6 are involved in the thiolꢀene reaction. Deꢀ
gree of substitution calculated according to the data of
acidꢀbase titration of the carboxy groups in the addition
product is lower as compared to the data of elemental
analysis, that is apparently explained by poor availability
of some acid groups for the ion exchange.
Earlier, NBu4F was suggested for the use as a catalyst
of thiolꢀene reactions involving phenylpropanoids. Howꢀ
ever, in our studies addition of NBu4F as a catalyst (7e)
Table 3. Thiolꢀene reaction of polysaccharide 6 and ,ꢀunꢀ
saturated acids: conditions and resultsa
c
Product
Starting acid
/h
DSSPh
I
II
7а
7b
7c
7d
7eb
8
Ferulic
24
10
24
48
24
24
24
0.00
0.19
0.34
0.38
0.11
0.37
0.32
0.00
0.12
0.26
0.27
0.08
0.30
0.26
Table 2. Bromination of compound 1 with a mixture of
Ph3P—NBS: conditions and results
4ꢀAcetoxyferulic
4ꢀAcetoxyferulic
4ꢀAcetoxyferulic
4ꢀAcetoxyferulic
4ꢀAcetoxycoumaric
4ꢀAcetoxysinapinic
Product
[Br] : [PS]*
(mol)
DSBr
Yield (%)
(on the mass of starting
polymer)
9
5а
5b
5c
2.0
1.0
0.5
1.19
0.57
0.28
52
90
93
a The results for the synthesis at 100 C and a 1.5 molar
excess of phenolic acid relative to thiol group.
b 20 mol.% of NBu4F was added.
c Degree of substitution (DSSPh) from the results of elemenꢀ
tal analysis (I) and titration (II).
* The molar ratio of brominating agent (Br) to polysaccharide
(PS) unit.

Phenylpropanoids derivatives of polysaccharides
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2133
method described earlier.10 Content of phenolic acids in polysacꢀ
charide (, wt.%) was determined spectrophotometrically acꢀ
cording to the method described earlier,11 using a UVꢀ1700
spectrophotometer (Shimadzu). For the HES esters containing
4ꢀacetoxyphenylcarboxylic acid fragments, as well as for esters
insoluble in water, this analysis was carried out after preliminary
hydrolysis of the ester bond and extraction of phenolic acids with
AcOEt (see Ref. 2). Degree of substitution (DSPh is the number
of added phenylpropanoids per one polysaccharide unit) in
the esterified polysaccharide derivatives were calculated using
the formula:
led to the decrease in the content of phenylpropanoic strucꢀ
tures in the polymer after the reaction of polysaccharide 6
and acetoxyferulic acids as compared to the results of this
reaction without source of fluoride ions. Analysis of the
products of the reaction between compounds 6 and acetꢀ
oxyferulic acid with NBu4F showed the presence of ferulic
acid among the lowꢀmolecularꢀmass products, that alꢀ
lowed us to draw a conclusion on the deacetylation of
acetoxyphenylpropenoic acid under these conditions. The
hydroxyphenylpropenoic acid formed does not react with
thiol, as shown for compound 7a, that leads to the formaꢀ
,
tion of derivatives with low DSSPh
.
In conclusion, we have synthesized hydroxyethyl starch
derivatives containing phenylpropanoic fragments, which
are grafted to the polysaccharide chain with ester and sulꢀ
fide bonds. For the preparation of the target modified
polysaccharides, we used esterification in aqueous organic
medium and thiolꢀene reaction involving mercaptodeꢀ
oxypolysaccharide and acetoxyphenylpropenoic acids.
Bromodeoxypolysaccharide synthesized as a precursor for
obtaining mercaptodeoxypolysaccharide has a significant
potential for further modification, including that which
suggests addition to this polysaccharide of various phenolꢀ
containing compounds.
The macromolecular compounds obtained in these
studies and containing phenylpropanoic structures, both
waterꢀsoluble and insoluble in water, are of interest priꢀ
marily as macromolecular antioxidants with the structure
close to the natural representatives. Sulfurꢀcontaining
polysaccharideꢀphenols are promising as components caꢀ
pable of modifying synthetic polymeric matrix in the techꢀ
nologies of preparation of thermoplastic polymeric mateꢀ
rials (plastic, rubber). The studies on the selection of conꢀ
ditions and catalysts for the reaction of ,ꢀunsaturated
phenolic acids with macromolecular thiols should be conꢀ
tinued, since this method is promising for obtaining new
compounds and materials on their basis with wide possiꢀ
bilities of application.
where Meu is the average molecular mass of the polysaccharide
elementary unit (182 g mol–1);  is the content of the correꢀ
pa
sponding phenolic acid, wt.%; Mpa is the molecular mass of the
phenolic acid fragment (which was 193, 163, and 223 g mol–1 for
ferulic, coumaric, and sinapinic acid, respectively).
Degree of substitution in the products of the thiolꢀene reacꢀ
tion (DSSPh) was determined using the elemental analysis data
and the results of the acidꢀbase titration. To carry out the titraꢀ
tion, a weighed amount of the sample (0.08—0.12 g) was left to
swell in DMSO (2 mL) for 3 h, then 0.1 N aqueous NaCl was
added. The concentration of the samples in solutions before tiꢀ
tration was 2.0 mg mL–1. The titration was carried out with 0.05 N
aqueous NaOH. The medium pH in all the experiments was
measured using an EkspertꢀpH ionometer (Ekonix, Russia) with
an ESKꢀ10601/7 combination electrode. Degree of substitution
was calculated using the formula:
,
where Meu = 190 g mol–1 is the average molecular mass of the
polysaccharide 6 elementary unit; n(COOH) is the content of
carboxy groups obtained from titration, mol; Mpa is the molecuꢀ
lar mass of the oxyphenylpropanoic acid fragment (Mpa = 195,
165, and 225 g mol–1 for the products of the reaction of 6 with
derivatives of ferulic, coumaric, and sinapinic acid, respectively).
3ꢀ(4ꢀAcetoxyꢀ3,5ꢀdimethoxyphenyl)propꢀ2ꢀenoic
acid
(4ꢀacetoxysinapinic acid). Sinapinic acid (2.0 g, 8.9 mmol) was
dissolved in dioxane (10 mL), followed by addition of aqueous
solution (50 mL) containing NaOH (0.92 g, 23 mmol). The
solution was cooled to 4 C and the first portion of Ac2O
(4.5 mmol) was added. The temperature of the reaction mixture
was raised to 25 C over next 30 min and the rest of Ac2O
(7.7 mmol) was added. After standing at 25 C for 1 h, the reacꢀ
tion mixture was acidified with 2 N aqueous H2SO4 to pH 4.5,
a precipitate formed was filtered off, washed with H2O until
neutrality, and recrystallized from aqueous (80%) EtOH. The
yield of the product was 78%. IR (КВr), /cm–1: 2944 (OH),
Experimental
The starting HES (DS = 0.5, MW = 200•103) (Serumwerk
Bernburg AG), ferulic (3ꢀ(4ꢀhydroxyꢀ3ꢀmethoxyphenyl)propꢀ
2ꢀenoic), pꢀcoumaric (3ꢀ(4ꢀhydroxy)propꢀ2ꢀenoic), and sinapꢀ
inic (3ꢀ(4ꢀhydroxyꢀ3,5ꢀdimethoxyphenyl)propꢀ2ꢀenoic) acids,
as well as NBu4F•3H2O, NBS, Ph3P, SOCl2 (SigmaꢀAldrich)
were used without preliminary purification. Ferulic and pꢀcouꢀ
maric acid acetates were obtained according to the method deꢀ
scribed earlier.6 The solvents DMAc and DMF were purified
and dried before used according to the known procedure.9
1H and 13C NMR spectra were recorded on a Bruker Avance
II 300 spectrometer (300.17 (1H) and 75.5 MHz (13C), solvent
DMSOꢀd6). IR spectra were recorded on a Shimadzu IR Presꢀ
tige 21 Fourierꢀtransform IR spectrometer. Elemental analysis
was carried out on a Vario Micro Cube Elementar CHNS anaꢀ
lyzer. Bromine in derivatives was determined according to the
1
1765 (AcOPh), 1664 (COOH). H NMR (DMSOꢀd6), : 2.268
(s, 3 H); 3.816 (s, 6 H); 6.61—6.67 (d, 1 H, J = 15.9 Hz); 7.12
(s, 2 H); 7.56—7.61 (d, 1 H, J = 15.9 Hz); 12.39 (s, 1 H). 13C NMR
(DMSOꢀd6), д: 20.58 (Me); 56.44 (OMe); 105.62 (C(2), C(6));
120.18 (C(8)); 129.94 (C(4)); 133.11 (C(1)); 144.23 (C(7));
152.44 (C(3), C(5)); 168.06 (COOH);168.14 (MeC(O)OPh).
Synthesis of acyl chlorides was accomplished by reflux of the
corresponding acetoxycinnamic acid with a threeꢀfold excess of

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Torlopov et al.
SOCl2 in CHCl3 in the presence of a catalytic amount of DMF
for 4 h with subsequent evaporation of the solvent in vacuo. The
chlorides were used in syntheses immediately after preparation
without additional purification.
3ꢀ(4ꢀAcetoxyꢀ3ꢀmethoxyphenyl)propꢀ2ꢀenoyl chloride. The
yield was 94%. 1H NMR (CDCl3),  2.35 (s, 3 H); 3.88 (s, 3 H);
6.57 (d, 1 H, J = 15.9 Hz); 7.09—7.12 (m, 3 H); 7.79 (d, 1 H,
J = 15.9 Hz); 12.39 (s, 1 H). 13C NMR (CDCl3), : 20.6 (Me);
56.4 (OMe); 111.9 (C(6)); 120.2 (C(8)); 123.6 (C(4)); 131.2
(C(1)); 142.8 (C(7)); 149.8 (PhC=C); 165.9 (COCl); 168.5
(MeC(O)OPh).
3ꢀ(4ꢀAcetoxyphenyl)propꢀ2ꢀenoyl chloride. The yield was
96%. 1H NMR (CDCl3), : 2.28 (s, 3 H); 6.78 (d, 1 H, J = 15.9 Hz);
7.22—7.24 (m, 2 H); 7.85—7.89 (d, 2 H). 13C NMR (CDCl3),
: 21.0 (Me); 122.4 (C(2), C(6)); 129.6 (C(3), C(5)); 142.8 (C(7));
148.8 (PhC=C); 166.6 (COCl); 169.0 (MeC(O)OPh).
3ꢀ(4ꢀAcetoxyꢀ3,5ꢀdimethoxyphenyl)propꢀ2ꢀenoyl chloride.
The yield was 96%. 1H NMR (DMSOꢀd6), : 2.26 (s, 3 H); 3.87
(s, 6 H); 6.59—6.63 (d, 1 H, J = 15.9 Hz); 7.13 (s, 2 H); 7.74—7.78
(d, 1 H, J = 15.9 Hz). 13C NMR (DMSOꢀd6), : 20.2 (Me); 56.4
(OMe); 105.4 (C(2), C(6)); 120.2 (C(8)); 129.31 (C(4)); 134.5
(C(1)); 144.9 (C(7)); 153.0 (C(3), C(5)); 166.64 (COCl); 168.14
(MeC(O)OPh).
Synthesis of 2Ac—4Ac (general method). Compound 1 (500 mg,
2.74 mmol) was dissolved in water (12 mL) with stirring under
nitrogen, then NaOH (an equimolar amount to the acyl chlorꢀ
ide) was added. A solution of phenylcarboxyl chloride in CHCl3
(10 mL) was added to the reaction mixture cooled to 4 C with
vigorous stirring. Then, the temperature of the reaction mixture
was raised to 25 C for 1 h, and the mixture was stirred for
another 5 h. To isolate the ester, the heterogeneous mixture was
acidified with 0.5 N HCl to pH 4.5 and poured into PriOH (200 mL).
A precipitate formed was separated by centrifugation, washed
with 70% aqueous EtOH and then subjected to freeze drying.
Oꢀ[3ꢀ(4ꢀAcetoxyꢀ3ꢀmethoxyphenyl)propꢀ2ꢀenoyl]ꢀOꢀ(2ꢀhydrꢀ
oxyethyl)ꢀ(14)--Dꢀglucan (ester of 4ꢀacetoxyferulic acid and
HES, 2Ac). Polysaccharide (380 mg) was obtained as a slightly
colored finely grained powder. IR (KBr), /cm–1: 3396 (OH);
2934 (CH2); 1761 (C=O, AcOPh); 1724 (C=O); 1634, 1510
(C—H, Ar); 1033 (C—O, carbohydrate skeleton). 13C NMR
(DMSOꢀd6), : 20.8 (Me); 56.5 (OMe); 60.8 (C(6), CH2CH2OH,
HES); 72.6 (C(2), C(3), CH2CH2OH, HES); 73.6 (C(5), HES);
80.3 (C(4), HES); 96.8 (C(1), HES, hydroxyethylated unit);
100.5 (C(1), HES); 112.2 (C(2)); 116.0 (C(8)), 121.6 (C(6));
123.8 (C(5)); 133.3 (C(1)); 141.5 (C(4)); 146.6 (C(7)); 151.7
(C(3)); 168.7 (C=O); 168.9 (MeC(O)OPh).
1597, 1506 (C—H, Ar). 13C NMR (DMSOꢀd6), : 20.6 (Me);
56.7 (OMe); 60.9 (C(6), CH2CH2OH, HES); 72.18—72.62
(C(2), C(3), CH2CH2OH, HES); 73.5 (C(5), HES); 79.2 (C(4),
HES); 79.7 (C(4), HES); 96.8 (C(1), HES, hydroxyethylated
unit); 100.7 (C(1), HES); 105.6 (C(2), C(6)); 120.2 (C(8)); 129.9
(C(4)); 133.1 (C(1)); 144.2 (C(7)); 152.4 (C(3), C(5)); 168.0
(C=O); 168.4 (MeC(O)OPh).
Removal of the acetyl protecting group from the phenol hydrꢀ
oxyl in the esters of HES and acetoxycinnamic acids (general
method). Esters 2Ac—4Ac (200 mg) were dissolved in DMAc
(3.0 mL), followed by addition of an aqueous solution of
MeCOONH4 (3.0 mL; 8 mol. equiv. of MeCOONH4 per 1 mol.
equiv. of the acetyl group). The mixture was stirred for 2 h at
25 C. Polysaccharide was precipitated by addition of PriOH
(25 mL). The precipitate was separated, washed with EtOH acidꢀ
ified with AcOH, then with EtOH, and subjected to freeze drying.
Oꢀ[3ꢀ(4ꢀHydroxyꢀ3ꢀmethoxyphenyl)propꢀ2ꢀenoyl]ꢀOꢀ(2ꢀ
hydroxyethyl)ꢀ(14)--Dꢀglucan (ester of HES and ferulic
acid, 2). Polysaccharide (170 mg) was obtained as a slightly
colored finely grained powder (DSPh = 0.29). IR (KBr), /cm–1
:
3408 (OH); 2934 (CH); 1719 (C=O); 1631, 1514 (C—H, Ar).
13C NMR (DMSOꢀd6), : 56.5 (OMe); 60.7 (C(6), CH2CH2OH,
HES); 71.59—72.61 (C(2), C(3), CH2CH2OH, HES); 73.6
(C(5), HES); 79.4 (C(4), HES); 96.7 (C(1), HES, hydroxyethylꢀ
ated unit); 100.7 (C(1), HES); 115.9 (C(8)); 126.1 (C(1)); 148.33
(C(3)); 149.6 (C(4)); 170.7 (C=O).
Oꢀ[3ꢀ(4ꢀHydroxyphenyl)propꢀ2ꢀenoyl]ꢀOꢀ(2ꢀhydroxyethyl)ꢀ
(14)--Dꢀglucan (ester of HES and pꢀcoumaric acid, 3).
Polysaccharide (180 mg) was obtained as a slightly colored finely
grained powder (DSPh = 0.31). IR (KBr), /cm–1: 3406 (OH);
2935 (CH2); 1709 (C=O); 1627, 1606, 1514 (C—H, Ar). 13C NMR
(DMSOꢀd6), : 61.0 (C(6), CH2CH2OH, HES); 70.37—72.76
(C(2), C(3), CH2CH2OH, HES); 73.7 (C(5), HES); 80.6 (C(4),
HES); 97.3 (C(1), HES, hydroxyethylated unit); 100.8 (C(1),
HES); 116.4 (C(8)); 123.0 (C(3), C(5)); 130.8 (C(2), C(6));
160.3 (C(4)).
Oꢀ[3ꢀ(4ꢀHydroxyꢀ3,5ꢀdimethoxyphenyl)propꢀ2ꢀenoyl]ꢀOꢀ(2ꢀ
hydroxyethyl)ꢀ(14)ꢀꢀDꢀglucan (ester of HES and sinapinic
acid, 4). Polysaccharide (167 mg) was obtained as a slightly colꢀ
ored finely grained powder (DSPh = 0.27). IR (KBr), /cm–1
:
3396 (OH); 2933 (CH); 1724 (C=O); 1634, 1587, 1510 (C—H, Ar).
13C NMR (DMSOꢀd6), : 56.7 (OMe); 61.0 (C(6), CH2CH2OH,
HES); 70.23—72.71 (C(2), C(3), CH2CH2OH, HES); 73.7
(C(5), HES); 81.1 (C(4), HES); 96.8 (C(1), HES, hydroxyethylꢀ
ated unit); 100.7 (C(1), HES); 106.8 (C(2), C(6)); 116.4 (C(8));
139.8 (C(4)); 149.2 (C(3); C(5)); 167.8 (C=O).
Oꢀ[3ꢀ(4ꢀAcetoxyphenyl)propꢀ2ꢀenoyl]ꢀOꢀ(2ꢀhydroxyethyl)ꢀ
(14)--Dꢀglucan (ester of HES and 4ꢀacetoxyꢀpꢀcoumaric
acid, 3Ac). Polysaccharide (366 mg) was obtained as a slightly
colored finely grained powder. IR (KBr), /cm–1: 3477 (OH);
2943 (CH); 1762 (C=O, AcOPh); 1719 (C=O); 1631, 1506 (C—H,
Ar). 13C NMR (DMSOꢀd6), : 60.8 (C(6), CH2CH2OH, HES);
72.20—72.73 (C(2), C(3), CH2CH2OH, HES); 73.5 (C(5),
HES); 80.3 (C(4), HES); 96.8 (C(1), HES, hydroxyethylated
unit); 100.7 (C(1), HES), 116.22 (C(8)); 122.9 (C(3), C(5));
129.85—130.80 (C(2), C(6)); 152.2 (C(4)), 160.0 (MeC(O)OPh).
Oꢀ[3ꢀ(4ꢀAcetoxyꢀ3,5ꢀdimethoxyphenyl)propꢀ2ꢀenoyl]ꢀOꢀ(2ꢀ
hydroxyethyl)ꢀ(14)--Dꢀglucan (ester of HES and 4ꢀacetoxyꢀ
sinapinic acid, 4Ac). Polysaccharide (370 mg) was obtained as
a slightly colored finely grained powder. IR (KBr), /cm–1: 3415
(OH); 2931 (CH); 1780 (C=O, AcOPh); 1701 (C=O); 1627,
6ꢀBromoꢀ6ꢀdeoxyꢀ[2ꢀOꢀ(2ꢀbromoethyl)]ꢀ(14)--Dꢀglucan
(bromodeoxy HES, 5). Compound 1 (5.00 g, 27.5 mmol) was
dissolved with heat in DMAc (100 mL) under argon. A solution
of the brominating system was prepared separately by mixing
Ph3P (7.21 g, 27.5 mmol) and NBS (4.90 g, 27.5 mmol) in DMAc
(100 mL) with cooling. The solution of the brominating system
was added to the solution of compound 1 and the homogeneous
mixture was heated for 3 h at 80 °C. Then, it was cooled down,
polysaccharide was precipitated with PriOH (1.0 L), the precipꢀ
itate was separated, sequentially washed with acetone and 70%
aqueous EtOH and dried in vacuo at 60 C to obtain polysacchaꢀ
ride 5 (4.60 g) with (Br) = 20.10 wt.%, DSBr = 0.57. IR (KBr),
/cm–1: 3423 (OH); 2931 (CH, CH2); 1452 (C—O—C); 1060
(C—O—C); 538 (C—Br). 13C NMR (75 MHz, DMSOꢀd6),
: 30.0 (CH2CH2Br); 35.0 (C(6), Br); 61.0 (C(6), CH2CH2OH,

Phenylpropanoids derivatives of polysaccharides
Russ.Chem.Bull., Int.Ed., Vol. 63, No. 9, September, 2014
2135
HES); 70.20—72.77 (C(2), C(3), CH2CH2OH, HES); 73.6
(C(5), HES); 80.5 (C(4), HES); 96.9 (C(1), HES, hydroxyethylꢀ
ated unit); 100.9 (C(1), HES).
Oꢀ{[1ꢀ(4ꢀHydroxyꢀ3,5ꢀdimethoxyphenyl)ꢀ2ꢀcarboxyethylꢀ
thio]ethyl}ꢀ(14)--Dꢀglucan (9). The product (0.34 g) was obꢀ
tained as a yellowish powder, DSSPh = 0.32. Found (%): C, 48.11;
H, 5.37; S, 6.34. Calculated (%): C, 48.13; H, 5.39; S, 6.34. IR
(KBr), /cm–1: 3441 (OH); 2927 (CH); 1712 (COOH); 1565,
1514 (C—H, Ar).
6ꢀDeoxyꢀ6ꢀmercaptoꢀ6ꢀ(2ꢀOꢀ(2ꢀmercaptoethyl)ꢀ(14)--
Dꢀglucan (mercaptodeoxy HES, 6). Polysaccharide 5 (3.00 g,
13.8 mmol) was dissolved in DMF (25 mL). Thiourea (5.25 g,
69.0 mmol) in DMF (25 mL) was added to the solution. The
mixture obtained was thermostated over 24 h at 80 C under
argon atmosphere. After cooling the mixture, polysaccharide
was precipitated with EtOH (1.0 L), washed with EtOH, and
poured into 2 N solution of NaOH in 70% aqueous EtOH. The
mixture was stirred for 3 h at 20 C. Then, the solution was
acidified with 2 N HCl, a precipitate was separated, washed with
70% aqueous EtOH, and subjected to freeze drying to obtain
polysaccharide 6 (2.20 g) with (S) = 8.46 wt.%, DSS = 0.52.
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 12ꢀ03ꢀ31216).
References
1. V. A. Kurkin, Chem. Nat. Compd. (Engl. Transl.), 2003, 39,
No. 2, 123 [Khim. Prirod. Soedin., 2003, 39, 87].
2. S. Mathew, T. E. Abraham, Food Chem., 2007, 105, 579.
3. M. A. Torlopov, E. V. Udoratina, A. V. Kuchin, Russ. J. Org.
Chem. (Engl. Transl.), 2013, 49, 702 [Zh. Org. Khim., 2013,
49, 719].
4. P. Kylli, P. Nousiainen, P. Biely, J. Sipilä, M. Tenkanen,
M. Heinonen, J. Agric. Food Chem., 2008, 56, 4797.
5. S. Gao, C Tseng, C. H. Tsai, C. Yao, Tetrahedron, 2008,
64, 1955.
6. A. Hosoda, E. Nomura, K. Mizuno, H. Taniguchi, J. Org.
Chem., 2001, 66, 7199.
7. A. L. Cimecioglu, D. H. Ball, D. L. Kaplan, S. H. Huang,
Macromolecules, 1994, 27, 2917.
8. H. Tseng, K. Furuhata, M. Sakamoto, Carbohydr. Res., 1995,
270, 149.
9. A. Gordon, R. Ford, The Chemists Companion, Wiley,
New York, 1972, 452.
Found (%): C, 44.70; H, 5.43; S, 8.46. Calculated for DSSH
=
= 0.52: C, 44.79; H, 5.60; S, 8.46. IR (KBr), /cm–1: 3442
(OH); 2927 (CH2); 2563 (SH).
Synthesis of compounds 7—9. Polysaccharide 6 (0.50 g,
2.6 mmol) was placed in DMF (3 mL). A solution of acetꢀ
oxyphenylpropenoic acid in DMF (3 mL; 1.5 molar excess relaꢀ
tive to the thiol group) was added to the solution under argon.
The reaction mixture was stirred for 24 h at 100 C under argon.
Homogenization of the reaction mixture was observed within
first 60 min the reaction. Then, the solvent was evaporated
in vacuo (65 C), the residue was washed with PriOH and poured
into 0.5 N aqueous NaOH (5 mL). The solution was allowed to
stand for 3 h, then the mixture was neutralized with 1.0 N HCl to
pH 2—3. A precipitate was sequentially washed with H2O and
70% aqueous EtOH and dried in vacuo at 60 C.
Oꢀ{[1ꢀ(4ꢀHydroxyꢀ3ꢀmethoxyphenyl]ꢀ2ꢀcarboxyethylthio]ꢀ
ethyl}ꢀ(14)--Dꢀglucan (7). The product (0.36 g) was obtained
as a yellowish powder, DSSPh = 0.34. Found (%): C, 48.11; H, 6.23;
S, 6.36. Calculated (%): C, 48.16; H, 6.26; S, 6.39. IR (KBr),
/cm–1: 3391 (OH); 2929 (CH2); 1701 (COOH); 1629, 1597,
1514 (C—H, Ar).
10. S. L. Kalinina, M. A. Motorina, N. I. Nikitina, N. A.
Khachapuridze, Analiz kondensatsionnykh polimerov [Analyꢀ
sis of Condensation Polymers], Moscow, Khimiya, 1984,
296 pp. (in Russian).
11. Y. Cho, S. Kim, C. Ahn, J. Je, Carbohydr. Polym., 2011,
83, 1617.
Oꢀ{[1ꢀ(4ꢀHydroxyphenyl)ꢀ2ꢀcarboxyethylthio]ethyl}ꢀ(14)-
-Dꢀglucan (8). The product (0.39 g) was obtained as a yellowish
powder, DSSPh = 0.37. Found (%): C, 49.24; H, 5.48; S, 6.54.
Calculated (%): C, 49.20; H, 5.52; S, 6.60. IR (KBr), /cm–1
:
Received December 3, 2013;
in revised form April 4, 2014
3441 (OH); 2927 (CH); 1712 (COOH); 1565, 1514 (C—H, Ar).