New disaccharide blocks for OSW-1 and its analogs

Article abstract of DOI:10.1134/S1070428012090163

Abstract-A new disaccharide block for OSW-1 natural steroidal antitumor agent was described. Regioisomeric 2- and 3-O-p-methoxybenzoyl derivatives of phenyl 1-thio-β-D-xylopyranoside and phenyl 2-O-acetyl-1- thio-β-L-arabinopyranoside derivatives blocked

Full text of DOI:10.1134/S1070428012090163

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 9, pp. 1238–1244. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © L.S. Khasanova, F.A. Gimalova, Z.R. Valiullina, N.K. Selezneva, R.M. Ganieva, L.V. Spirikhin, M.S. Miftakhov, 2012, published in
Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 9, pp. 1239–1245.
New Disaccharide Blocks for OSW-1 and Its Analogs
L. S. Khasanova, F. A. Gimalova, Z. R. Valiullina, N. K. Selezneva, R. M. Ganieva,
L. V. Spirikhin, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: bioreg@anrb.ru
Received December 30, 2011
Abstract—A new disaccharide block for OSW-1 natural steroidal antitumor agent was described. Regioiso-
meric 2- and 3-O-p-methoxybenzoyl derivatives of phenyl 1-thio-β-D-xylopyranoside and phenyl 2-O-acetyl-1-
thio-β-L-arabinopyranoside derivatives blocked at positions 3 and 4 by R3Si groups were synthesized with
a view to use them in the preparation of OSW-1 analogs modified at the disaccharide fragment.
DOI: 10.1134/S1070428012090163
Cholestane glycoside OSW-1 (I) isolated from the
bulbs of the South African plant Ornithogalum
saundersiae possesses a very high cytotoxicity against
a broad series of malignant tumor cells [1, 2]. The
concentration of OSW-1 in the bulbs of Ornithogalum
saundersiae is extremely low, so that required amounts
of this steroidal glycoside can be obtained only by
chemical synthesis [3–5]. The synthesis of OSW-1
analogs modified at both aglycone [6–9] and disaccha-
ride fragments [10–12] was the subject of numerous
studies. Modification of both parts of OSW-1 gives
rise to different cytotoxic properties of its analogs. The
disaccharide fragment of I consists of 2-O-acetyl-L-
arabinose and 2-O-(p-methoxybenzoyl)-D-xylose resi-
dues linked through 1→3 glycoside bond.
were synthesized starting from known phenyl 1-thio-
glycosides III and IV [3] (Scheme 1).
Scheme 1.
OMe
t-BuMe2SiO
O
O
O
Me
Me
O
SPh
O
OAc
OMe
OH
OC(O)C6H4OMe-4
II
O
O
OH
+
HO
HO
SPh
SPh
HO
OAc
III
IV
We believed that the most efficient method for
coupling the glycosyl donor with aglycone in the final
step of construction of molecule I is the trichloroacet-
imidate procedure [5] which involves transformation
of the anomeric hydroxy group in the disaccharide
block into trichloroacetimidoyloxy group. The latter is
readily replaced under catalysis by strong Lewis acids.
The resulting C1-carbenium intermediate reacts at the
16-OH group in the aglycone. Hydrolysis of disaccha-
ride II at the phenyl thioacetal center, followed by
trichloroacetimidation, could lead to the corresponding
glycosyl donor.
O
Me
Me
Me
OH
Me
Me
H
O
O
H
H
AcO
O
OH
HO
O
OC(O)C6H4OMe-4
OH
HO
I
We initially tried to synthesize C4-blocked com-
pound II [13] via direct reaction of diol III with
imidate V, which seemed to be promising. However,
the products were regioisomeric disaccharides VI and
In the present article we describe a new disac-
charide building block II for OSW-1, as well as some
derivatives of its monosaccharide constituents which
1238

NEW DISACCHARIDE BLOCKS AND CONSTITUENTS FOR OSW-1 AND ITS ANALOGS
1239
Scheme 2.
OMe
OMe
HO
O
(1) 4-Å mol. sieves
(2) BF3·Et2O, CH2Cl2
NH
O
O
O
O
O
Me
Me
O
Me
Me
SPh
III
+
O
O
CCl3
OAc
OMe
OMe
OC(O)C6H4OMe-4
OC(O)C6H4OMe-4
V
VI
SPh
OAc
OMe
O
O
O
Me
Me
O
O
+
HO
OMe
OC(O)C6H4OMe-4
VII
VII. Compound VI is C4-deprotected diastereoisomer
of II differing from the latter by configuration of the
C1′–O glycoside bond (Scheme 2).
diol IV with 1.3 equiv of chloroacetyl chloride in
benzene in the presence of triethylamine were also
unsuccessful; in this case uncontrolled formation of
regioisomeric mono- and disubstituted products was
observed.
We presumed that change of configuration at C1′ is
affected by the unprotected OH group on C4 and per-
formed the reaction with the C4-protected derivative.
Preliminarily, glycosyl acceptors protected at the 4-OH
group that are necessary for the synthesis of II were
prepared from L-arabinose. Selective protection of the
axial 4-OH group in III was achieved using triethyl-
silyl trifluoromethanesulfonate at low temperature [3]
(Scheme 3). However (see below), further synthesis of
disaccharide II from silyl ether VIII in the presence of
a strong Lewis acid (BF3·Et2O, NIS–TFA, TfOH) was
complicated because of partial hydrolysis of the tri-
ethylsilyl group. Therefore, triethylsilyl protection was
replaced by more stable tert-butyldimethylsilyl group.
Silylation of diol III with tert-butyldimethylsilyl tri-
fluoromethanesulfonate occurred neither at –78°C [3]
nor at 0°C nor at 20°C. Acceptable results were ob-
tained using the system tert-butyl(chloro)dimethyl-
silane–imidazole–CH2Cl2 in the presence of 4-dimeth-
ylaminopyridine at room temperature. Monosubstitut-
ed compounds IX and X thus formed at a ratio of 3:1
were separated by column chromatography on silica
gel. Attempts to perform selective chloroacetylation of
The structure of regioisomeric silyl ethers IX and X
1
was assigned on the basis of the H NMR data. The
1H NMR spectra of IX and X differed by the position
of signals from 3-H and 4-H and methyl protons in the
silyl moiety. The positions of the 3-H and 4-H signals
of IX differed by Δδ ~0.3 ppm, whereas the corre-
sponding signals of X almost coincided with each
other and appeared as a narrow two-proton multiplet.
This may be due to leveling effect of the OAc group
on C2, and downfield shift of the 3-H signal may be
related to the effect of the OSiMe2Bu-t group on C4.
Methyl groups in the silyl fragment of isomer IX gave
rise to a six-proton singlet, while those in X resonated
each as a separate singlet. Obviously, free rotation
about the C3–OSi bond in molecule X is hindered, so
that the methyl groups on the silicon are shielded to
different extents.
As glycosyl donor for the synthesis of disaccharide
II we planned to use imidate V [13] which was pre-
pared according to Scheme 4. In doing so, it was desir-
able to optimize the stage of synthesis of precursor of
the corresponding 3,4-bis-acetal via direct reaction of
arabinopyranose phenyl thioacetal IV with butane-2,3-
dione. The reaction was not selective, and it produced
a 3:1 mixture of the target 3,4-bis-acetal and 2,3-iso-
mer as by-product. In order to develop an alternative
approach to compound XIV, we studied direct p-me-
thoxybenzoylation of IV. For this purpose, we applied
carbodiimide procedure with the use of a slight excess
of 4-methoxybenzoic acid. However, the major prod-
uct was 3-O-acyl derivative XV (Scheme 5).
Scheme 3.
OH
OR
i–iii
O
O
SPh
SPh
HO
R'O
OAc
OAc
VIII–XI
III
VIII, R = Et3Si, R′ = H; IX, R = t-BuMe2Si, R′ = H; X; R =
H, R′ = t-BuMe2Si; XI, R = R′ = ClCH2C(O); i: Et3SiOTf,
CH2Cl2, 2,4-dimethylpyridine, –78oC; ii: t-BuMe2SiCl,
CH2Cl2, imidazole, 4-dimethylaminopyridine, 20°C;
iii: Et3N, ClCH2COCl, PhH, 20°C.
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KHASANOVA et al.
1240
Scheme 4.
OMe
O
O
HO
Me
SPh
O
O
O
Me
Me
SPh
IV
+
O
OH
MeO
Me OMe
OMe
XII
3:1
XIII
OMe
OMe
O
O
O
O
O
Me
Me
SPh
Me
Me
OC(=NH)CCl3
OC(O)C6H4OMe-4
XII
O
OC(O)C6H4OMe-4
XIV
OMe
OMe
V
Scheme 5.
4-MeOC6H4COOH
DCC, DMAP, CH2Cl2
O
O
HO
HO
HO
4-MeOC6H4C(O)O
SPh
SPh
OH
OH
IV
XV
O
O
4-MeOC6H4C(O)O
Me
SPh
O
O
4-MeOC6H4C(O)O
HO
HO
O
SPh
SPh
HO
OH
OC(O)C6H4OMe-4
MeO
Me OMe
XVIII
XVII
XVI
The structure of XV was proved by comparing its
Rf values (TLC) and spectral parameters (including
HSQC correlation data) with those of regioisomeric
compounds XVI and XVII obtained by acid hydrolysis
of bis-acetals XIV and XVIII (the latter were de-
scribed previously [13]). It should be noted that diol
XV failed to react with butane-2,3-dione under the
conditions of synthesis of XIV.
XIX–XXI necessary for subsequent transformations
(Scheme 6).
In the final step of our study we examined the key
coupling of imidate V with glycosyl acceptors VIII
and IX, promoted by BF3·Et2O [14]. The reaction of
equimolar amounts of imidate V, alcohol VIII, and
BF3·Et2O in methylene chloride at –40°C gave a com-
plex mixture of products, presumably due to instability
of triethylsilyl ether VIII under these conditions.
Better results were obtained using more stable tert-
butyldimethylsilyl ether IX. The reaction of IX with V,
other conditions being equal, afforded targeted disac-
Diols XV and XVII are appropriate building blocks
for the synthesis of C3- and C4-p-methoxybenzoyloxy
derivatives. Following standard procedures, diol XV
was converted into completely blocked derivatives
Scheme 6.
ClCH2COOH, DCC, DMAP
or Et3SiCl, pyridine
or TBDMSOTf, pyridine, DMAP
O
RO
SPh
XV
4-MeOC6H4C(O)O
OR
XIX–XXI
XIX, R = ClCH2C(O); XX, R = Et3Si; XXI, R = t-BuMe2Si.
Scheme 7.
OMe
(1) 4-Å mol. sieves, CH2Cl2
(2) BF3·Et2O, –40°C
O
O
Me
Me
OC(=NH)CCl3
OC(O)C6H4OMe-4
O
+
IX
II
OMe
V
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

NEW DISACCHARIDE BLOCKS AND CONSTITUENTS FOR OSW-1 AND ITS ANALOGS
1241
charide II in a moderate yield (50%; Scheme 7).
β-Configuration of the glycoside moiety in II was con-
firmed by the presence of a characteristic doublet from
warm up to room temperature, the organic phase was
separated, the aqueous phase was extracted with
methylene chloride, the extracts were combined with
the organic phase, washed with a solution of NaCl,
dried over MgSO4, and evaporated, and the residue
was subjected to chromatography on silica gel using
benzene as eluent. Yield 0.16 g (76%), [α]D20 = –29.7
(c = 0.69, CHCl3); published data [5]: [α]D20 = –33.6°
1
1′-H at δ 4.75 ppm (J = 7.4 Hz) in the H NMR spec-
trum and C1′ signal at δC 103.35 ppm (1JCH = 160 Hz)
in the 13C NMR spectrum. The 5′-H proton
(δ 3.46 ppm) displayed a vicinal coupling constant
3J of 10 Hz with 4′-H and a long-range coupling con-
stant with 3′-H (4J = 2.0 Hz), indicating mutual W-
orientation of 5′-H and 3′-H. In keeping with the
HSQC data, the C3 and C3′ signals of II coincided with
each other in the 13C NMR spectrum (δC 75.17 ppm).
1
(c = 0.7, CHCl3). H NMR spectrum (CDCl3), δ, ppm:
0.63 q (6H, SiCH2, J = 7.89 Hz), 0.96 t (9H, CH3, J =
7.89 Hz), 2.10 s (3H, CH3CO), 2.56 d (1H, OH, J =
5.2 Hz), 3.52 d.d (1H, J = 3.10, 11.6 Hz) and 4.14 d.d
(1H, J = 6.98, 11.6 Hz) (OCH2), 3.75 m (1H, 3-H),
4.03 m (1H, 4-H), 4.97 d (1H, 1-H, J = 4.9 Hz),
5.18 d.d (1H, 2-H, J = 5.8, 5.0 Hz), 7.25 m (3H) and
7.48 m (2H) (C6H5). 13C NMR spectrum, δC, ppm: 4.71
(SiCH2), 6.58 (CH3), 20.89 (CH3CO), 63.82 (C5),
67.31 (C4), 70.51 and 71.95 (C3, C2), 85.23 (C1);
127.26, 128.73, 131.53, 134.85 (Ph); 169.79 (C=O).
To conclude, we have synthesized new mono- and
disaccharide blocks for the synthesis of saponin
OSW-1 (I) and its analogs. The newly synthesized
compounds are characterized by acceptable chemical
stability, and optimal conditions for their preparation
have been found.
EXPERIMENTAL
Reaction of compound III with tert-butyl-
(chloro)dimethylsilane. 4-Dimethylaminopyridine,
50 mg, was added at 0°C to a solution of 0.60 g
(2.11 mmol) of compound III and 0.18 g (2.64 mmol)
of imidazole in 3 ml of methylene chloride, 0.36 g
(2.39 mmol) of tert-butyl(chloro)dimethylsilane was
then added in portions, and the mixture was stirred for
10 h at room temperature and washed in succession
with water and brine. The organic phase was dried
over MgSO4 and evaporated, and the residue was
subjected to chromatography on silica gel using first
benzene and then petroleum ether–ethyl acetate (10:1)
as eluents to isolate 0.04 g (5%) of doubly protected
derivative, 0.22 g (26%) of IX, 0.14 g (17%) of X, and
0.260 g of mixture IX/X (overall yield 74%) which
was separated by repeated chromatography.
The IR spectra were recorded on a Shimadzu IR
Prestige-21 spectrometer from samples prepared as
thin films or dispersed in mineral oil. The H and
1
13C NMR spectra were measured on Bruker AM-300
(300.13 and 75.47 MHz, respectively) and Bruker
Avance-500 (500.13 and 125.77 MHz, respectively)
spectrometers using tetramethylsilane as internal refer-
ence. The optical rotations were determined on
a Perkin Elmer-341 polarimeter. The mass spectra
were run on a Thermo Finnigan MAT 95XP instrument.
The elemental compositions were determined on
a Euro-2000 CHNS(O) analyzer; the results were con-
sistent with the calculated values. The progress of
reactions was monitored by TLC on Sorbfil plates
(Krasnodar, Russia); spots were detected by treatment
with an acidified solution of 4-methoxybenzaldehyde
in ethanol. Reaction products were isolated by column
chromatography on silica gel (30–60 g of the sorbent
per gram of substrate); freshly distilled solvents were
used as eluents.
Phenyl 2-O-acetyl-4-O-tert-butyldimethylsilyl-1-
thio-β-L-arabinopyranoside (IX). [α]D20 = –27.0° (c =
1
1.0, CHCl3). H NMR spectrum (CDCl3), δ, ppm:
0.10 s (6H, SiCH3), 0.90 s (9H, t-Bu), 2.10 s (3H,
CH3CO), 2.50 d (1H, OH, J = 5.3 Hz), 3.53 d.d (1H,
OCH2, J = 3.2, 11.7 Hz), 3.75 m (1H, 4-H), 4.03 m
(1H, 3-H), 4.15 d.d (1H, OCH2, J = 6.8, 11.8 Hz),
4.90 d (1H, 1-H, J = 5.0 Hz), 5.18 t (1H, 2-H, J =
5.5 Hz), 7.30 m (3H) and 7.50 m (2H) (C6H5).
13C NMR spectrum, δC, ppm: –2.00 and –1.74 (SiCH3),
17.95 (CMe3), 20.96 (CH3CO), 25.69 (CH3), 64.14
(C5), 67.69 (C4), 70.70 and 71.82 (C2 and C3), 85.14
(C1); 127.40, 128.82, 131.79, 134.42 (Ph); 169.89
(C=O). Mass spectrum, m/z (Irel, %): 398 (0.1) [M]+,
289 (28) [M – SPh]+, 229 (100) [M – SPh – AcOH]+,
Phenyl 2-O-acetyl-4-O-triethylsilyl-1-thio-β-L-
arabinopyranoside (VIII). Phenyl 2-O-acetyl-1-thio-
β-L-arabinopyranoside (III), 0.15 g (0.528 mmol), was
dissolved in 5 ml of methylene chloride, 0.12 ml of
2,4-dimethylpyridine was added, the mixture was
cooled to –60°C, 0.14 ml (0.62 mmol) of triethylsilyl
trifluoromethanesulfonate was added, and the mixture
was stirred for 1 h at –60°C and for 1 h at –78°C.
A saturated solution of sodium hydrogen carbonate,
2 ml, was added at –60°C, the mixture was allowed to
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

KHASANOVA et al.
1242
(OCH3), 69.58 (C5), 69.41 and 72.11 (C3, C4), 79.17
(C2), 80.01 (C1); 115.10, 124.23, 128.71, 130.38,
133.05, 133.21, 135.71, 165.10 (Carom); 166.77 (C=O).
Mass spectrum, m/z (Irel, %): 267 (28) [M – SPh]+, 249
(5), 135 (100) [MeOC6H4C≡O]+, 115 (48), 97 (10).
189 (44), 171 (30), 117 (32), 73 (83). Found:
m/z 398.131 [M]+. C19H30O5SSi. Calculated: M 398.138.
Phenyl 2-O-acetyl-3-O-tert-butyldimethylsilyl-1-
thio-β-L-arabinopyranoside (X). [α]D20 = –34.0° (c =
1
1.0, CHCl3). H NMR spectrum (CDCl3), δ, ppm:
Phenyl 2-O-(4-methoxybenzoyl)-1-thio-β-D-xylo-
pyranoside (XVI). Aqueous trifluoroacetic acid,
0.66 ml, was added to a solution of 0.05 g
(0.102 mmol) of compound XIV in 1 ml of methylene
chloride. The mixture was stirred at room temperature
until the initial compound disappeared (TLC), diluted
with 2 ml of methylene chloride, washed with saturat-
ed solutions of sodium hydrogen carbonate and sodium
chloride, dried over MgSO4, and evaporated, and the
residue was purified by column chromatography on
silica gel using petroleum ether–ethyl acetate (2:1) as
eluent. Yield 0.03 g (78%), [α]D20 = –23.0° (c = 0.5,
0.14 s and 0.18 s (3H each, SiCH3), 0.94 s (9H, t-Bu),
2.09 s (3H, CH3CO), 2.29 d (1H, OH, J = 6.3 Hz),
3.58 d.d (1H, OCH2, J = 3.4, 11.9 Hz), 3.89 m (2H,
3-H, 4-H), 4.17 d.d (1H, OCH2, J = 6.3, 11.9 Hz),
4.92 d (1H, 1-H, J = 5.64 Hz), 5.14 t (1H, 2-H, J =
5.64 Hz), 7.24–7.29 m (3H) and 7.45–7.47 m (2H)
(C6H5). 13C NMR spectrum, δC, ppm: –4.65 and
–5.05 (SiCH3), 17.95 (CMe3), 20.94 (CH3CO), 25.66
(CH3), 63.89 (C5), 66.89 (C4), 70.96 and 72.14 (C2,
C3), 85.98 (C1); 127.27, 128.78, 131.44, 135.19 (Ph);
169.39 (C=O).
Phenyl 1-thio-β-D-xylopyranoside (IV) was syn-
thesized by reaction of 0.19 g (0.5 mmol) of phenyl
2,3,4-tri-O-acetyl-1-thio-D-xylopyranoside [13] with
1.2 mg (0.12 mmol) of sodium methoxide. The product
was isolated by column chromatography on silica gel
using chloroform–methanol (10:1) as eluent. Yield
0.1 g (83%), [α]D20 = –25.2° (c = 0.505, CHCl3).
1H NMR spectrum (CDCl3), δ, ppm: 3.10 m (2H, OH),
3.83 m (3H, 2-H, 3-H, OH), 3.58 d (1H, OCH2, J =
12.0 Hz), 3.69 m (1H, 4-H), 4.08 m (1H, OCH2),
5.47 m (1H, 1-H), 7.28 m (3H) and 7.52 m (2H)
(C6H5). 13C NMR spectrum, δC, ppm: 70.55 (C5), 71.10
and 73.93 (C3, C4), 79.22 (C2), 90.32 (C1); 128.97,
130.31, 133.47, 135.04 (Ph).
1
CHCl3). H NMR spectrum (CDCl3), δ, ppm: 2.01 br.s
(1H, OH), 3.24 m (1H, OH), 3.35 t (1H, OCH2, J =
11.3 Hz), 3.74 m (2H, 3-H, 4-H), 3.83 s (3H, OCH3),
4.16 d.d (1H, OCH2, J = 11.3, 4.4 Hz), 4.81 d (1H,
1-H, J = 9.3 Hz), 4.94 t (1H, 2-H, J = 8.4 Hz), 6.89 d
and 7.99 d (2H each, C6H4, J = 8.9 Hz), 7.23 m (3H)
and 7.39–7.42 m (2H) (C6H5). 13C NMR spectrum, δC,
ppm: 55.49 (OCH3), 69.06 (C5), 69.77 and 73.08
(C3, C4), 76.60 (C2), 86.54 (C1); 113.82, 121.45,
128.03, 128.97, 132.26, 132.50, 132.59, 163.93
(Carom); 166.76 (C=O).
Phenyl 4-O-(4-methoxybenzoyl)-1-thio-D-xylo-
pyranoside (XVII) was synthesized in a similar way
from 0.05 g (0.102 mmol) of XVIII [13]. Yield
0.032 g (83%), [α]D20 = +23.0° (c = 0.5, CHCl3).
1H NMR spectrum (CDCl3), δ, ppm: 1.90 br.s (1H,
OH), 3.14 m (1H, OH), 3.36 m (1H, 3-H), 3.44 d.d
(1H, OCH2, J = 11.3, 9.9 Hz), 3.49 t (1H, 2-H, J =
8.9 Hz), 3.86 s (3H, OCH3), 4.29 d.d (1H, OCH2, J =
5.4, 11.6 Hz), 4.60 d (1H, 1-H, J = 9.3 Hz), 5.04 m
(1H, 4-H, J = 5.2 Hz), 6.91 d (2H, J = 8.6 Hz) and
7.98 d (2H, J = 8.9 Hz) (C6H4), 7.33 m (3H) and 7.56–
7.59 m (2H) (C6H5). 13C NMR spectrum, δC, ppm:
55.31 (OCH3), 66.45 (C5), 71.15 and 72.24 (C3 and
C4), 75.36 (C2), 88.23 (C1); 113.55, 121.45, 128.11,
128.90, 131.44, 131.52, 131.82, 132.86, 133.79,
163.59 (Carom); 165.80 (C=O).
Phenyl 3-O-(4-methoxybenzoyl)-1-thio-β-D-xylo-
pyranoside (XV). Compound IV, 0.5 g (2.0 mmol),
was dissolved in 10 ml of CH2Cl2–MeCN (1:1), 0.38 g
(2.4 mmol) of 4-methoxybenzoic acid and 0.125 g
(1.02 mmol) of 4-dimethylaminopyridine were added,
the mixture was cooled to 0°C, 0.46 g (2.4 mmol) of
N,N′-dicyclohexylcarbodiimide in 3 ml of methylene
chloride was added, and the mixture was stirred for
24 h at room temperature. The product was separated
from unreacted compound IV by column chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(2:1) as eluent. Yield 0.3 g (40%), [α]D20 = –47.5° (c =
1
0.04, CHCl3). H NMR spectrum (CDCl3), δ, ppm:
2.90 br.s (1H, OH), 3.52 d.d (1H, OCH2, J = 8.8,
11.5 Hz), 4.14 d.d (1H, OCH2, J = 4.6, 11.5 Hz),
3.66 m (1H, 4-H), 3.88 s (3H, OCH3), 4.64 d (1H, OH,
J = 5.7 Hz), 4.79 d (1H, 3-H, J = 6.4 Hz), 4.94 d (1H,
1-H, J = 7.96 Hz), 5.19 t (1H, 2-H, J = 7.96 Hz),
7.04 d (2H, J = 9.07 Hz) and 8.04 d (2H, J =
9.06 Hz) (C6H4), 7.29–7.38 m (3H) and 7.54–7.57 m
(2H) (C6H5). 13C NMR spectrum, δC, ppm: 56.57
Phenyl 2,4-di-O-chloroacetyl-3-O-(4-methoxy-
benzoyl)-1-thio-D-xylopyranoside (XIX). Compound
XV, 1.10 g (3.0 mmol), was dissolved in 10 ml of
CH2Cl2–MeCN (1:1), 0.69 g (7.5 mmol) of chloro-
acetic acid and 0.13 g (1.39 mmol) of 4-dimethyl-
aminopyridine were added under stirring, the mixture
was cooled to 0°C, and 1.50 g (7.5 mmol) of N,N′-di-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

NEW DISACCHARIDE BLOCKS AND CONSTITUENTS FOR OSW-1 AND ITS ANALOGS
1243
cyclohexylcarbodiimide in 5 ml of methylene chloride
was added dropwise. The mixture was stirred at room
temperature until the initial compound disappeared
(TLC), diluted with 20 ml of methylene chloride, and
washed with a saturated solution of NaHCO3. The
organic phase was dried over MgSO4 and evaporated,
and the residue was purified by column chromatog-
raphy on silica gel using petroleum ether–ethyl acetate
(2:1) as eluent. Yield 1.2 g (87%), [α]D20 = +24.0° (c =
0.03, CHCl3). IR spectrum, ν, cm–1: 2980, 2933, 2854,
1773, 1730, 1686, 1605, 1512, 1373, 1317, 1258,
1169, 1089, 1067, 1028, 995, 847, 814, 748, 692, 424,
Phenyl 2,4-di-O-(tert-butyldimethylsilyl)-3-O-
(4-methoxybenzoyl)-1-thio-D-xylopyranoside (XXI).
A solution of 0.10 g (0.26 mmol) of compound XV
and 0.007 g (0.057 mmol) of 4-dimethylaminopyridine
in 5 ml of pyridine was cooled to 0°C, and 0.18 ml
(0.80 mmol) of tert-butyldimethylsilyl trifluoro-
methanesulfonate was added under stirring. The mix-
ture was stirred first for 30 min at 0°C and then at
60°C until the initial compound disappeared (TLC),
5 ml of methanol was added, and the mixture was
diluted with ethyl acetate, washed in succession with
ice water, 10% aqueous HCl, and brine, dried over
MgSO4, and evaporated. The residue was purified by
column chromatography on silica gel using petroleum
ether–ethyl acetate (2:1) as eluent. Yield 0.12 g (75%),
1
415. H NMR spectrum (CDCl3), δ, ppm: 3.63 d.d
(1H, J = 7.74, 11.95 Hz) and 4.43 d.d (1H, J = 4.42,
11.94 Hz) (OCH2), 3.86 s (3H, OCH3), 4.01 s (2H) and
4.04 d (2H, J = 2.43 Hz) (CH2Cl), 4.99 d (1H, 1-H, J =
7.52 Hz), 5.18 m (2H, 4-H, 2-H), 5.48 t (1H, 3-H, J =
8.84 Hz), 6.93 d (2H, J = 8.85 Hz) and 7.98 d (2H, J =
9.07 Hz) (C6H4), 7.34–7.36 m (3H) and 7.50–7.53 m
(2H) (C6H5). 13C NMR spectrum, δC, ppm: 40.43
(CH2Cl), 55.42 (OCH3), 64.15 (C5), 69.63 (C4), 70.82
and 71.11 (C3, C2), 85.23 (C1); 113.86, 120.67, 128.44,
129.11, 132.11, 132.95, 163.99 (Carom); 164.89, 165.88,
166.34 (C=O).
[α]D20 = +1.8° (c = 0.44, CHCl3). H NMR spectrum
1
(CDCl3), δ, ppm: –0.19 s, –0.18 s, –0.12 s, and –0.02 s
(3H each, SiMe2); 0.72 s and 0.82 s (9H each, t-Bu),
3.36 t (1H, J = 11.06 Hz) and 3.99 d.d (1H, J = 5.34,
11.3 Hz) (OCH2), 3.79 t (1H, 2-H, J = 8.85 Hz), 3.86 s
(3H, OCH3), 3.87 m (1H, 4-H), 4.72 d (1H, 1-H, J =
9.07 Hz), 5.29 t (1H, 3-H, J = 8.84 Hz), 6.94 d (2H,
J = 8.85 Hz) and 8.03 d (2H, J = 9.06 Hz) (C6H4),
7.25–7.35 m (3H) and 7.51 d (2H, J = 7.96 Hz) (C6H5).
13C NMR spectrum, δC, ppm: –5.04, 4.59, and 3.75
(SiCH3); 25.45 and 25.96 (CH3), 55.42 (OCH3), 69.87
(C5), 69.58 (C4), 72.36 and 79.38 (C3, C2), 90.58 (C1);
113.55, 123.04, 127.41, 129.06, 130.11, 131.98,
134.55, 163.31 (Carom); 165.11 (C=O).
Phenyl 3-O-(4-methoxybenzoyl)-2,4-di-O-tri-
ethylsilyl-1-thio-D-xylopyranoside (XX). Chlorotri-
ethylsilane, 0.79 ml (4.70 mmol), was added under
stirring at 20°C to a solution of 0.44 g (1.17 mmol) of
compound XV in 5 ml of pyridine, and the mixture
was stirred at 20°C until the initial compound disap-
peared (~4 h, TLC). The mixture was then diluted with
ethyl acetate, washed with ice water, 10% aqueous
HCl, and brine, dried over MgSO4, and evaporated.
The residue was purified by column chromatography
on silica gel using first petroleum ether and then petro-
leum ether–ethyl acetate (3:1) as eluents. Yield 0.32 g
Phenyl 3,4-O-(2,3-dimethoxybutane-2,3-diyl)-
2-O-(4-methoxybenzoyl)-β-D-xylopyranosyl(1→3)-
2-O-acetyl-4-O-tert-butyldimethylsilyl-1-thio-α-L-
arabinopyranoside (II). Finely ground freshly cal-
cined 4-Å molecular sieves, 5 mg, were added to
a mixture of 0.03 g (0.047 mmol) of compound V [13]
and 0.019 g (0.047 mmol) of IX in anhydrous methy-
lene chloride. The mixture was stirred for 30 min at
room temperature and cooled to –70°C, 0.0235 ml of
a 0.1 M solution of BF3·Et2O in methylene chloride
was added, and the mixture was stirred for 30 min at
–70°C and for 2 h at –40°C. The reaction was termi-
nated by adding triethylamine, the mixture was fil-
tered, the filtrate was evaporated, and the residue was
purified by column chromatography on silica gel using
petroleum ether–ethyl acetate (10:1, 5:1, 2:1) as
eluent. Yield 0.021 g (~50%), [α]D20 = +16.0° (c = 1.0,
(45%), [α]D20 = +24.0° (c = 0.115, CHCl3). H NMR
1
spectrum (CDCl3), δ, ppm: 0.46 q (6H, SiCH2, J = 8.1,
7.5 Hz), 0.56 q (6H, SiCH2, J = 8.1, 7.6 Hz), 0.81 t
(9H, CH3, J = 8.2, 7.8 Hz), 0.88 t (9H, CH3, J =
7.8 Hz), 3.37 t (1H, OCH2, J = 10.3 Hz), 4.00 d.d (1H,
OCH2, J = 5.0, 11.0 Hz), 3.79 t (1H, 2-H, J = 9.0 Hz),
3.88 s (3H, OCH3), 3.92 m (1H, 4-H, J = 9.0 Hz),
4.72 d (1H, 1-H, J = 9.2 Hz), 5.26 t (1H, 3-H, J =
8.7 Hz), 6.89 d (2H, J = 8.84 Hz) and 8.0 d (2H, J =
8.8 Hz) (C6H4). 7.25 m (3H) and 7.46 d (2H, J =
6.42 Hz) (C6H5). 13C NMR spectrum, δC, ppm: 4.67
and 5.31 (SiCH2), 6.55 and 6.84 (CH3), 55.34 (OCH3),
69.35 (C4), 69.87 (C5), 72.49 and 79.22 (C3, C2), 90.52
(C1); 113.48, 122.93, 127.37, 128.88, 131.27, 131.74,
134.42, 163.28 (Carom); 165.01 (C=O).
1
CHCl3). H NMR spectrum (CDCl3), δ, ppm: –0.01 s
(6H, SiMe2), 0.96 s (9H, t-Bu), 1.22 s (3H, CH3),
1.27 s (3H, CH3), 2.03 s (3H, CH3CO), 3.15 s (3H,
2
OCH34), 3.26 s (3H, OCH3), 3.46 t.d (1H, 5′-H, J =
10.5, J = 2.0 Hz), 3.77 d.d (1H, 3′-H, J = 4.0, 10.2,
4J = 2.0 Hz), 3.83–3.97 m (5H, OCH2, OCH), 3.87 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 9 2012

KHASANOVA et al.
1244
3. Deng, S.J., Yu, B., Lou, Y., and Hui, Y.Z., J. Org.
Chem., 1999, vol. 64, p. 202.
4. Ma, X., Yu, B., Hui, Y., Miao, Z., and Ding, J.,
Carbohydr. Res., 2001, vol. 334, p. 159.
5. Yu, W.S. and Jin, Z.D., J. Am. Chem. Soc., 2002,
vol. 124, p. 6576.
6. Deng, L., Wu, H., Yu, B., Jiang, M., and Wu, J., Bioorg.
Med. Chem. Lett., 2004, vol. 14, p. 2781.
7. Matsuya, Y., Itoh, T., and Nemoto, H., Eur. J. Org.
Chem., 2003, p. 2221.
8. Shi, B., Wu, H., Yu, B., and Wu, J., Angew. Chem., Int.
Ed., 2004, vol. 43, p. 4324.
(3H, OCH3), 4.41 t (1H, OCH2, J = 10.2 Hz), 4.75 d
(1H, 1′-H, J = 7.4 Hz), 5.02 d.d (1H, 2-H, J = 2.1,
4.4 Hz), 5.09 br.s (1H, 1-H), 5.12 d.d (1H, 2′-H, J =
7.4, 10.2 Hz), 6.92 d.d (2H, C6H4, J = 1.9, 7.4 Hz),
7.19–7.28 m (3H) and 7.45 m (2H) (C6H5), 7.98 d.d
(2H, C6H4, J = 1.5, 7.5 Hz). 13C NMR spectrum, δC,
ppm: –5.04 and –4.98 (SiCH3), 17.52 (CH3), 17.63
(CH3), 18.20 (CMe3), 21.06 (CH3), 25.81 (CMe3),
47.61 (OCH3), 47.93 (OCH3), 55.41 (OCH3), 63.97
(C5, C5′), 65.63 (C4), 71.13 (C2′), 71.32 (C4′), 74.56
(C2), 75.17 (C3, C3′), 86.10 (C1), 99.46 and 99.73 (C2″,
C3″), 103.35 (C1′); 113.54, 122.53, 126.97, 128.75,
131.21, 131.71, 163.30 (Carom); 164.40, 169.36 (C=O).
Mass spectrum, m/z (Irel, %): 750 (0.2) [M]+, 749 (0.5)
[M – H]+, 381 (68), 135 (100) [COC6H4OCH3]+.
Found: m/z 750.299 [M]+. C36H50O13SSi. Calculated:
M 750.274.
9. Wojtkielewicz, A., Dugosz, M., Maj, J., Morzycki, J.W.,
Nowakowski, M., Renkiewicz, J., Strnad, M., Swaczy-
nov, J., Wilczewska, A.Z., and Wjcik, J., J. Med. Chem.,
2007, vol. 50, p. 3667.
10. Tang, P., Mamdani, F., Hu, X., Liu, J.O., and Yu, B.,
Bioorg. Med. Chem. Lett., 2007, vol. 17, p. 1003.
This study was performed under financial support
by the Russian Foundation for Basic Research (project
no. 11-03-00780a).
11. Zheng, D., Zhou, L., Guan, Y., Chen, X., Zhou, W.,
Chen, X., and Lei, P., Bioorg. Med. Chem. Lett., 2010,
vol. 20, p. 5439.
12. Guan, Y., Zheng, D., Zhou, L., Wang, H., Yan, Zh.,
Wang, N., Chang, H., She, P., and Lei, P., Bioorg. Med.
Chem. Lett., 2011, vol. 21, p. 2921.
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