Synthesis of 2-deoxy-d-arabino/lyxo-hexopyranosyl disaccharides

Article abstract of DOI:10.1016/j.carres.2007.11.017

Synthesis of 2-deoxy-d-arabino/lyxo-hexopyranosyl disaccharides is reported. In these, the disaccharides contain 2-deoxy-arabino-hexopyranosyl and 2-deoxy-lyxo-hexopyranosyl sugars as either the reducing or the non-reducing or both the sugar units of the

Full text of DOI:10.1016/j.carres.2007.11.017

Available online at www.sciencedirect.com
Carbohydrate Research 343 (2008) 453–461
Synthesis of 2-deoxy-D-arabino/lyxo-hexopyranosyl disaccharides
Somak Paul and Narayanaswamy Jayaraman*
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560 012, India
Received 4 September 2007; received in revised form 4 November 2007; accepted 15 November 2007
Available online 23 November 2007
Abstract—Synthesis of 2-deoxy-D-arabino/lyxo-hexopyranosyl disaccharides is reported. In these, the disaccharides contain 2-
deoxy-arabino-hexopyranosyl and 2-deoxy-lyxo-hexopyranosyl sugars as either the reducing or the non-reducing or both the sugar
units of the disaccharides. The activated 2-deoxy-1-thioglycosides served as the common precursors to prepare the 2-deoxy disac-
charides with the above configurations.
Ó 2007 Elsevier Ltd. All rights reserved.
Keywords: Deoxysugars; Glycals; Glycosylations; Thioglycosides
1. Introduction
2-deoxy-lyxo-hexopyranosyl sugars as either the reduc-
ing or the non-reducing or both the sugar units of the
disaccharides. 2-Deoxy disaccharides with maltose and
lactose configuration are studied previously in detail.
For example, the 2-deoxy maltosyl oligosaccharides have
been studied to understand the enzymatic glycosylations
and the functions of enzyme, such as amylases,
glycosylases and cyclodextrin-glucano-transferases.6
The 2-deoxylactose derivatives, on the other hand, are
known to be the high-affinity substrates for bacterial
phosphotransferases7 and the enzymatic products of
galactosyltransferases.8 The readily available 2-deoxy-
thioglycosides have thus been considered as suitable
precursors to synthesize 2-deoxy sugar containing
disaccharides. Synthesis of six new 2-deoxy-arabino-
hexopyranosyl and 2-deoxy-lyxo-hexopyranosyl sugar
containing disaccharides are described in this report.
These are (i) 2-deoxy-a-D-arabino-hexopyranosyl-(1!4)-
D-glucopyranose (20-deoxy maltose); (ii) a-D-gluco-
pyranosyl-(1!4)-2-deoxy-D-arabino-hexopyranose (2-
deoxy maltose); (iii) 2-deoxy-a-D-arabino-hexopyranos-
yl-(1!4)-2-deoxy-D-arabino-hexopyranose (2,20-dideoxy
maltose); (iv) 2-deoxy-a-D-lyxo-hexopyranosyl-(1!4)-
D-glucopyranose; (v) 2-deoxy-a-D-lyxo-hexopyranosyl-
(1!4)-2-deoxy-D-arabino-hexopyranose and (vi) b-D-
galactopyranosyl-(1!4)-2-deoxy-D-arabino-hexopyrano-
side (2-deoxy lactose).
Among various deoxy sugars, 2-deoxysugars assume
significance as integral components of several natural
products.1 The biological functions of, for example,
antibiotics require the presence of the deoxy sugar units
in these molecules.2 Associated with the importance of
2-deoxy sugar units for biological functions, a number
of synthetic methods have been developed.3 An
approach relying on utilizing an activated 2-deoxy-1-
thioglycoside has been developed by us recently. An easy
access to activated 2-deoxy-1-thioglycoside involves the
reaction of readily available 1,2-unsaturated sugars,
namely glycals, with EtSH in the presence of catalytic
amount of ceric ammonium nitrate (CAN).4 The syn-
thetic utility of the activated 2-deoxy-1-thioglycoside
has been established in glycosylations involving both
aglycosyl and glycosyl acceptors.4 Methods have also
been established to prepare either anomers of aryl
2-deoxy-glycosides, from activated 2-deoxy-1-thioglyco-
side donors.5 Continuing our efforts, the synthesis of
2-deoxy disaccharides were undertaken. These disaccha-
rides contain 2-deoxy-arabino-hexopyranosyl and
*
Corresponding author. Tel.: +91 80 394 2578; fax: +91 80 360
0683; e-mail: jayaraman@orgchem.iisc.ernet.in
0008-6215/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.11.017

454
S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
2. Results and discussion
performed subsequently: (i) O-benzoylation of 2 with
BzCl and pyridine; (ii) deprotection of benzylidene
group and (iii) the reaction of the resulting product with
nBu2SnO, followed by treatment with BzCl afforded the
acceptor alcohol 3, in an overall yield of 44%, on the
basis of 1 (Scheme 1).
2.1. Synthesis of 20-deoxy- and 2,20-dideoxy-disaccharides
Synthesis of this series of disaccharides was accom-
plished through a glycosylation between a 2-deoxy
glycosyl donor and appropriately protected either a
glycosyl or a 2-deoxyglycosyl acceptor. The formation
of the a-glycosidic linkage was anticipated from the
2-deoxy glycosyl donor, due to the absence of neigh-
bouring group effects. Also, the formation of the
a-glycosidic linkage with 2-deoxy-1-thioglycoside donor
was established previously.4,5 The required acceptors for
glycosylation with 2-deoxy-1-thioglycoside having free
hydroxyl group at C-4 were synthesized as described
below.
2.1.2. Synthesis of benzyl 2-deoxy-3,6-di-O-acetyl-D-
arabino-hexopyranoside (6). Synthesis of 6 was initi-
ated from the known 2-deoxy-1-thioglycoside 4.4 Glyco-
sylation of BnOH with 4, followed by de-O-acetylation
led to isolation of benzyl 2-deoxy-arabino-hexopyrano-
side (5) (Scheme 2). Partial acetylation of 5 was
performed with AcCl upon the reaction of 5 with
nBu2SnO, to afford alcohol 6, in an overall yield of
67%, on the basis of 4.
The glycosylation reactions were then performed,
involving acceptors 3 and 6 and the donor 4 and ethyl
2-deoxy-3,4,6-tri-O-acetyl-1-thio-D-lyxo-hexopyranoside
(7).4 Syntheses of 20-deoxy maltose (12) and 2,20-dideoxy
maltose (14) were thus accomplished by the reaction of
2-deoxy-1-thioglycoside 4, with acceptors 3 and 6,
promoted by NIS/TfOH (Schemes 3 and 4). The
glycosylations led to the isolation of disaccharides 8
2.1.1. Synthesis of p-methoxybenzyl 2,3,6-tri-O-benzoyl-
b-D-glucopyranoside (3). Synthesis of the acceptor 3
was performed with a modification of a known proce-
dure.9 Thus, reaction of acetobromo glucose (1)10 with
p-methoxybenzyl alcohol (PMB–OH), followed by
de-O-acetylation and 4,6-O-benzylidination afforded
diol 2 (Scheme 1). The following reactions were
H
BzO
AcO
O
Ph
a, b, c
d, e, f
O
O
AcO
AcO
O
O
HO
HO
BzO
OPMB
O
AcO
BzO
HO
Br
1
OMe
2
PMB = p-methoxy benzyl
3
˚
Scheme 1. Reagents and conditions: (a) Ag2O, PMB–OH, I2 (cat.), 4 A MS, CH2Cl2, rt, 24 h; (b) NaOMe (cat.), MeOH, rt, 6 h; (c) a,a-
n
dimethoxytoluene, p-TsOH, DMF, 60 °C, 2 mm of Hg, 1.5 h; (d) BzCl, C5H5N, 0 °C–rt, 24 h; (e) p-TsOH, MeOH/THF (1:1), 3 h; (f) (i) Bu2SnO,
PhMe, reflux, 16 h; (ii) BzCl, rt, 5 min.
AcO
AcO
AcO
AcO
HO
AcO
HO
HO
c
a, b
O
O
O
HO
SEt
OBn
OBn
6
4
5
n
˚
Scheme 2. Reagents and conditions: (a) BnOH, NIS, TfOH (cat.), 4 A MS, CH2Cl2, 0 °C, 30 min; (b) NaOMe (cat.), MeOH, rt, 6 h; (c) (i) Bu2SnO,
MeOH, reflux, 16 h; (ii) AcCl, PhMe, rt, 1 h.
OH
OAc
O
HO
HO
O
b, c
a
AcO
AcO
OH
OBz
4 +
3
O
O
O
O
BzO
OPMB
HO
OH
OH
8
12
OBz
˚
Scheme 3. Reagents and conditions: (a) NIS, TfOH (cat.), 4 A MS, CH2Cl2, 0 °C, 30 min; (b) CAN, MeCN/H2O (9:1 v/v), rt, 4 h; (c) NaOMe (cat.),
MeOH, rt, 6 h.

S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
455
OH
OH
O
HO
HO
O
c
a, b
HO
HO
OH
OH
4 +
6
O
O
O
O
HO
HO
OH
10
14
OBn
˚
Scheme 4. Reagents and conditions: (a) NIS, TfOH (cat.), 4 A MS, CH2Cl2, 0 °C, 30 min; (b) NaOMe (cat.), MeOH, rt, 6 h; (c) H2, Pd/C (10%),
MeOH, rt, 3 d.
and 10. Subsequent deprotection afforded disaccharides
12 and 14.
(J1,2e ꢀ 2.0 Hz and J 1,2a ꢀ 10.0 Hz). The above observa-
tions for H-10 and H-1 resonances for the monodeoxy
(12, 13) and dideoxy (14, 15) disaccharides indicated
the presence of a-anomeric configuration at the non-
reducing end and a mixture of a- and b-anomeric config-
urations at the reducing end of the disaccharides. The a/
b ratio of the anomeric configurations at the reducing
end was found to be ꢀ2:1, in all the disaccharides.
Similarly, glycosylation of acceptors 3 and 6 with
2-deoxy-1-thioglycoside 7 provided protected disaccha-
rides 9 and 11 (Schemes 5 and 6). Deprotection of the
protecting groups in 9 and 11 afforded the free hydroxyl
group containing disaccharides 13 and 15.
The anomeric configurations of the newly formed
glycosidic linkages were confirmed by 1H and 13C
NMR spectroscopies. In the case of 8 and 9, the H-10
appeared as an apparent doublet at ꢀ5.20 ppm
(J1,2 ꢀ 4.0 Hz). The dideoxy disaccharides 10 and 11
showed anomeric H-10 resonance at ꢀ5.32 ppm, with
J1,2 ꢀ 3.0 Hz. The anomeric H-1 in 10 and 11 resonated
at ꢀ4.92 ppm and 4.34 ppm, corresponding to the pres-
ence of a- and b-anomeric configuration at the reducing
end of the disaccharides.
13
In C NMR spectrum of 12–15, the C-10 nuclei
appeared at 98.5 ppm, whereas the C-1 appeared as
the set of resonances at ꢀ91 ppm and 93–96 ppm. These
observations further confirmed the a-anomeric configu-
ration at the non-reducing end and a,b-anomeric mix-
tures at the reducing end of the disaccharides.
2.2. Synthesis of 2-deoxy disaccharides
An analysis of the anomeric protons in the case of free
mono- and dideoxy disaccharides 12–15 showed the
following trend: (i) H-10 in 12 and 13 resonated at
5.35 ppm as an apparent doublet with J1,2a ꢀ 2.7 Hz;
(ii) H-1 resonated at ꢀ5.06 ppm (J1,2a ꢀ 3.6 Hz) and at
4.50 ppm (J1,2 ꢀ 7.8 Hz); (iii) H-10 in 14 and 15 appeared
at ꢀ5.50 ppm as a broad singlet and (iv) H-1 in 14 and 15
appeared at 5.35 ppm (J1,2a ꢀ 3.0 Hz) and 4.91 ppm
The preparations of 2-deoxy disaccharides were per-
formed directly from the 1,2-unsaturated disaccharide
glycals. It is noted that disaccharide glycals have been
shown before as precursors for the synthesis of 2-deoxy
disaccharides. Maltal and lactal have been subjected to
hydration across the vinylic double bond, under the
acid-catalyzed condition, to form 2-deoxy maltose11a
and 2-deoxy lactose, respectively.11b In the present
AcO
AcO
OAc
HO
HO
OH
AcO
AcO
OAc
O
O
b, c
OPMB
a
OBz
O
OH
3
+
O
O
O
O
HO
SEt
BzO
9
7
OBz
13
OH
OH
˚
Scheme 5. Reagents and conditions: (a) NIS, TfOH (cat.), 4 A MS, CH2Cl2, 0 °C, 30 min; (b) CAN, MeCN/H2O (9:1 v/v), rt, 4 h; (c) NaOMe (cat.),
MeOH, rt, 6 h.
HO
HO
OH
HO
HO
OH
AcO
AcO
OAc
O
O
a, b
c
OH
O
OH
+
6
O
O
HO
O
O
HO
SEt
7
11
15
OH
OBn
˚
Scheme 6. Reagents and conditions: (a) NIS, TfOH (cat.), 4 A MS, CH2Cl2, 0 °C, 30 min; (b) NaOMe (cat.), MeOH, rt, 6 h; (c) H2, Pd/C (10%),
MeOH, rt, 3 d.

456
S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
study, it was intended to explore the 2-deoxy-1-thiogly-
coside route to prepare the 2-deoxydisaccharides. Thus,
hexa-O-acetyl maltal (16)12 and hexa-O-acetyl lactal
(17)12 were converted to the corresponding 2-deoxy-1-
thioglycosides 18 and 19, respectively, by treatment with
EtSH/CAN reagent system (Scheme 7). The yields were
poor, only 10–15% of 18 and 19 were obtained, the
remaining products were found to be 2,3-unsaturated
thioglycosides, corresponding to the Ferrier products.
With a desire to obtain 2-deoxy-1-thioglycoside disac-
charides in higher yields, an alternate procedure was
undertaken. In this procedure, the glycals 16 and 17
were converted first to C-1 acetylated 2-deoxy disaccha-
rides 20 and 21, respectively, utilizing the method by
Lam and Gervey-Hague.13 Thus, the glycals 16 and 17
were treated with HBr/AcOH, followed by treatment
with Ac2O/AcOH that led to the formation of 20 and
21 (Scheme 8). The C-1 acetylated 2-deoxy disaccharides
20 and 21 were subjected subsequently to a reaction with
BF3–Et2O and EtSH at ꢁ40 °C, which furnished
2-deoxythioglycosides 18 and 19. The overall yield of
the formation of 18 and 19 were ꢀ75%, on the basis
of glycals 16 and 17. Thus, an alternative method of
synthesizing the activated 2-deoxy-1-thioglycosides has
also been identified, which does not require reaction
with CAN. Hydrolysis of the thioglycosides in 18 and
19 was conducted in the presence of NBS in acetone–
H-1 proton of the reducing end. The anomeric H-1
was observed as a set of resonances corresponding to
a- and b-configurations, in the order: (i) 5.04 ppm for
22 and 5.39 ppm for 23; (ii) 4.90 ppm (J1,2e ꢀ 2.0 Hz
and J1,2a ꢀ 10.0 Hz) for 22 and 4.33 ppm as a multiplet
for 23. The anomeric C-10 resonated at 95.4 ppm and
102.9 ppm, for 22 and 23, respectively. The C-1 nucleus
of the a-anomer was observed at 92.2 and 93.1 ppm for
22 and 23, respectively. The corresponding values for
the b-anomer were observed at 94.5 ppm for 22 and
98.0 ppm for 23.
In conclusion, a series of 2-deoxy, 20-deoxy and 2,20-
dideoxy disaccharides, presenting arabino-hexopyrano-
syl and lyxo-hexopyranosyl sugar units, were prepared
through glycosylations involving 2-deoxy-1-thioglyco-
side donors. Activated 2-deoxy-1-thioglycoside disac-
charide donors have also been explored to secure the
2-deoxy disaccharides. Few of the 20-deoxy- and 2,20-
dideoxy disaccharides are known previously through
enzymatic methods.6–8,14 The glycosylations studied
herein, involving orthogonally protected 2-deoxy-1-thio-
glycosides, allow the preparation of a range of 2 or 20-
monodeoxy and 2,20-dideoxy disaccharides.
3. Experimental
´
H2O, followed by de-O-acetylation under Zemplen
3.1. General methods
condition, that afforded 2-deoxydisaccharides 22 and
23, in good yields. Alternatively, the disaccharides 22
and 23 could also be secured by direct de-O-acetylation
Chemicals were purchased from commercial sources and
were used without further purification. Solvents were
dried and distilled according to the literature proce-
dures. Analytical TLC was performed on commercial
Merck plates coated with Silica Gel GF254 (0.25 mm).
Silica gel (100–200 mesh) was used for column chroma-
tography. Optical rotations were recorded on a Jasco
´
of 20 and 21, under Zemplen condition.
The constitutions of 22 and 23 were established by 1H
13
and C NMR spectroscopies. The anomeric H-10 ap-
peared at 5.30 ppm, as a broad singlet for 22, whereas
that for 23 was observed at 4.33 ppm, overlapped with
OAc
O
OH
O
OAc
O
OAc
O
OH
O
OAc
O
AcO
R1
AcO
R1
b, c
SEt
HO
R1
O
a
O
O
AcO
HO
AcO
OH
R2
R2
R2
OAc
OAc
OH
16: (1-4)α linkage: R1 = OAc, R2 = H
17: (1-4)β linkage: R1 = H, R2 = OAc
18: (1-4)α linkage: R1 = OAc, R2 = H
19: (1-4)β linkage: R1 = H, R2 = OAc
22: (1-4)α linkage: R1 = OH, R2 = H,
23: (1-4)β linkage: R1 = H, R2 = OH
Scheme 7. Reagents and conditions: (a) CAN (cat.), EtSH, MeCN, 0 °C–rt, 16 h; (b) NBS, acetone/H2O (5:1, v/v), rt, 5 min; (c) NaOMe (cat.),
MeOH, rt, 1 h.
OH
O
OAc
O
OH
O
OAc
O
a
b
HO
R1
AcO
R1
O
O
16 or 17
HO
AcO
OH
R2
R2
OAc
OH
OAc
20: (1-4)α linkage: R1 = OAc, R2 = H
21: (1-4)β linkage: R1 = H, R2 = OAc
22: (1-4)α linkage: R1 = OH, R2 = H,
23: (1-4)β linkage: R1 = H, R2 = OH
Scheme 8. Reagents and conditions: (a) HBr/AcOH (cat.) (33% w/v), Ac2O, AcOH, CH2Cl2, 0 °C–rt, 16 h; (b) NaOMe (cat.), MeOH, rt, 6 h.

S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
457
Model P-1020 polarimeter at the sodium D line at 24 °C.
High-resolution mass spectra were obtained from
Q-TOF instrument by electron spray ionization (ESI)
technique. 1H and 13C NMR spectral analysis were
performed on a 300/400 MHz and 75/100 MHz spectro-
meter, respectively, with residual solvent signal acting as
the internal standard. The following abbreviations were
used to explain the multiplicities: s, singlet; d, doublet; t,
triplet; m, multiplet; band, several overlapping signals;
br, broad.
(ddd, 1H, J = 3.8, 4.5, 9.3 Hz, H-4), 3.79–3.75 (band,
4H, H-5, OCH3), 3.50 (d, 1H, J = 4.5 Hz, –OH); 13C
NMR (CDCl3, 75 MHz): d 167.4, 166.9, 165.2, 159.4,
133.5, 133.4, 130.0, 129.9, 129.8, 129.6, 129.3, 128.9,
128.6, 128.5, 128.4, 128.3, 113.7, 98.7 (C-1), 74.5 (C-2),
71.4 (C-3, PhCH2), 70.1 (C-4), 69.7 (C-5), 63.5 (C-6),
55.2 (OCH3). HR-MS m/z: [M+Na]+ calcd for
C35H32O10, 635.1893; found, 635.1919.
3.3. Benzyl 2-deoxy-3,6-di-O-acetyl-D-arabino-hexo-
pyranoside (6)
3.2. 4-Methoxybenzyl 2,3,6-tri-O-benzoyl-b-D-gluco-
pyranoside (3)
A mixture of benzyl 2-deoxy-D-arabino-hexopyranoside
(5)4 (1.23 g, 4.86 mmol) and nBu2SnO (2.49 g,
0.01 mol) was dissolved in MeOH (40 mL) and refluxed
for 16 h. The solvents were evaporated and the resulting
residue was dried at 60 °C, dissolved in PhMe (20 mL)
and AcCl (728 lL, 0.01 mol) was added. After stirring
for 1 h in room temperature, the solvents were evapo-
rated and the crude product was purified to obtain 6
(1.31 g, 80%, a/b = 2:1), as a gum, along benzyl 2,3,6-
tri-O-acetyl-2-deoxy-D-arabino-hexopyranoside (0.22 g,
12%). Rf = 0.48 (1:1 EtOAc/pet ether); 1H NMR
(CDCl3, 300 MHz): d 7.35–7.27 (band, aromatic), 5.20
(ddd, J = 5.4, 9.3, 12.0 Hz, H-3b), 5.00 (d, J = 3.0 Hz,
H-1a), 4.93–4.79 (m, H-4b, PhCH2), 4.69–4.58 (m,
PhCH2), 4.50–4.43 (m, H-1b, H-5a, H-6aa, H-6ab),
4.37 (dd, J = 2.1, 12.3 Hz, H-6ba), 4.25 (dd, J = 2.1,
12.0 Hz, H-6bb), 3.85 (ddd, J = 2.1, 4.8, 9.9 Hz, H-5b),
3.54–3.40 (m, H-3a, H-4a), 3.29–3.25 (band, –OH),
2.33–2.20 (m, H-2aa, H-2eb), 2.13–2.09 (band, COCH3),
1.80–1.63 (m, H-2ea, H-2ab); 13C NMR (CDCl3,
75 MHz): d 171.6, 171.5, 171.4, 171.1, 137.1, 136.9,
128.3, 127.9, 127.8, 127.7, 98.0 (C-1b), 96.1 (C-1a),
74.0, 73.3, 71.9, 70.4, 70.3, 69.6, 69.0, 68.9, 63.4, 63.3,
36.9 (C-2b), 34.7 (C-2a), 21.0, 20.9, 20.8. HR-MS m/z:
[M+Na]+ calcd for C17H22O7, 361.1263; found,
361.1261.
To a mixture of BzCl (3 mL, 0.042 mol) and pyridine
(6 mL) in CH2Cl2 (15 mL), 4-methoxybenzyl 4,6-O-ben-
zylidene-b-D-glucopyranoside (2)9 (3.68 g, 0.012 mol) in
CH2Cl2 (15 mL) was added dropwise at 0 °C. After 24 h,
the reaction mixture was diluted with CH2Cl2 (50 mL),
washed with ice-cold aq HCl (5%) solution, satd aq
NaHCO3 solution, water, dried (Na2SO4) and concen-
trated. The resulting crude 4-methoxybenzyl 2,3-di-O-
benzoyl-4,6-O-benzylidene-b-D-glucopyranoside (5.5 g)
was dissolved in MeOH/THF (20 mL, 1:1, v/v) and
was added with p-TsOH (2.46 g). After 3 h, the reaction
was quenched with Et3N (4 mL), concentrated and puri-
fied by column chromatography (SiO2, 100–200 mesh)
to afford 4-methoxybenzyl 2,3-di-O-benzoyl-b-D-gluco-
pyranoside (4.37 g, 86%, after 2 steps), as a foamy solid.
Rf = 0.27 (1:1 EtOAc/PhMe); 1H NMR (CDCl3,
300 MHz): d 7.95–7.07 (m, 10H, aromatic), 7.08 (d,
2H, J = 8.6 Hz, aromatic), 6.68 (d, 2H, J = 8.6 Hz, aro-
matic), 5.43 (dd, 1H, J = 7.8, 9.3 Hz, H-2), 5.33 (app. t,
1H, J = 9.3 Hz, H-3), 4.78 (d, 1H, J = 12.3 Hz, PhCH2),
4.59 (d, 1H, J = 7.8 Hz, H-1), 4.67 (d, 1H, J = 12.3 Hz,
PhCH2), 4.02–3.74 (m, 3H, H-6a, H-6b, H-5), 3.73 (s,
3H, OCH3), 3.55–3.49 (m, 1H, H-4), 3.33 (br s, 2H,
–OH); 13C NMR (CDCl3, 75 MHz): d 167.5, 159.3,
133.5, 133.2, 129.9, 129.8, 129.5, 129.3, 129.0, 128.8,
128.6, 128.4, 128.3, 113.7, 99.1 (C-1), 76.5 (C-2), 75.8
(C-3), 71.4 (PhCH2), 70.6 (C-4), 69.9 (C-5), 62.2 (C-6),
55.2 (OCH3). HR-MS m/z: [M+Na]+ calcd for
C28H28O9, 531.1631; found, 531.1635.
3.4. 4-Methoxybenzyl 4-O-(2-deoxy-3,4,6-tri-O-acetyl-a-
D-arabino-hexopyranosyl)-2,3,6-tri-O-benzoyl-b-D-gluco-
pyranoside (8)
A suspension of nBu2SnO (2.9 g, 0.01 mol), 4-
methoxybenzyl 2,3-di-O-benzoyl-b-D-glucopyranoside
(4.37 g, 9.6 mmol) in PhMe was refluxed, with azotropic
removal of water. After 16 h, the reaction mixture was
cooled, BzCl (1.34 mL, 0.012 mol) was added and stir-
red for 5 min. Removal of the solvent and purification
of the resulting residue afforded 3 (4.90 g, 93%), as a foa-
Compound 44 (0.31 g, 0.93 mmol) and 3 (0.31 g,
0.51 mmol) were dissolved in CH2Cl2 (10 mL) and stir-
˚
red for 1 h in the presence of 4 A MS (0.8 g), under
N2 atmosphere. N-Iodosuccinimide (0.25 g, 1.12 mmol)
and catalytic TfOH (10 lL, 0.11 mmol) were added at
0 °C, stirred for 30 min. and neutralized with a few
drops of Et3N. The reaction mixture was diluted with
CH2Cl2 (25 mL), filtered and the filtrate was washed
with aq Na2S2O3 solution, brine, dried and concen-
trated. Purification of the crude product afforded disac-
charide 8 (0.25 g, 55%), as a white foamy solid.
24
my solid. Rf = 0.43 (20% EtOAc/PhMe); ½aꢂD +24.8 (c
1
1.1, CHCl3); H NMR (CDCl3, 300 MHz): d 8.13–7.25
(m, 15H, aromatic), 7.09 (d, 2H, J = 8.7 Hz, aromatic),
6.68 (d, 2H, J = 8.7 Hz, aromatic), 5.49 (dd, 1H,
J = 7.8, 9.3 Hz, H-2), 5.38 (app. t, 1H, J = 9.3, H-3),
4.84–4.59 (m, 5H, H-1, H-6a, H-6b, PhCH2), 3.91
24
Rf = 0.20 (EtOAc/pet ether 1:2); ½aꢂD +38.6 (c 1.04,
1
CHCl3); H NMR (CDCl3, 300 MHz): d 8.16–7.35 (m,

458
S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
15H, aromatic), 7.07 (d, 2H, J = 8.7 Hz, aromatic), 6.68
(d, 2H, J = 8.7 Hz, aromatic), 5.67 (app. t, 1H,
J = 9.0 Hz, H-3), 5.42 (dd, 1H, J = 7.8, 9.0 Hz, H-2),
5.19 (d, 1H, J = 3.6 Hz, H-10), 4.88–4.53 (m, 7H,
PhCH2, H-1, H-6a, H-6b, H-30, H-40), 4.28–4.13 (m,
3H, H-5, H-60a; H-6b0 ), 4.04 (ddd, 1H, J = 3.5, 4.7,
9.0 Hz, H-50), 3.86–3.75 (band, 4H, H-4, OCH3), 2.13–
1.89 (band, 11H, COCH3, H-20 ; H-20 ); 13C NMR
(CDCl3, 75 MHz): d 170.5, 169.8, 169.7, 166.1, 165.3,
165.1, 159.3, 133.5, 133.4, 133.1, 130.0, 129.8, 129.8,
129.7, 129.6, 129.5, 128.3, 128.2, 113.7, 98.4 (C-1), 98.3
(C-10), 75.5, 75.4, 72.7, 71.7, 70.1, 69.2, 68.9, 68.0,
63.4, 62.0, 55.1 (OCH3), 34.7 (C-20), 20.7, 20.6. HR-
MS m/z: [M+Na]+ calcd for C47H48O17, 907.2789;
found, 907.2783.
(cat.) and MeOH (8 mL), stirred for 6 h at room temper-
ature, quenched with a few drops of AcOH/MeOH
(1:10, v/v) and concentrated. Purification afforded 10
(0.28 g, 66% conversion after 2 steps, a/b = 2:1), as a
1
white foamy solid. Rf = 0.34 (12% MeOH/CHCl3); H
NMR (D2O, 300 MHz): d 7.26–7.23 (band, aromatic),
5.32 (app. d, J = 2.7 Hz, H-10), 5.07 (m, H-3b), 4.93
(br s, H-1a), 4.82–4.64 (band, H-30, H-40, PhCH2,
H-5a, H-4b), 4.52–4.49 (m, H-6aa, H-6ba), 4.35 (app.
d, J = 11.3 Hz, H-1b), 3.85–3.13 (band, H-50,
H-60 ; H-60 , H-3a, H-4a, H-6ab, H-6bb, H-5b), 2.08–
a
e
a
b
1.78 (m, H-2eb, H-20 ; H-20 , H-2aa, H-2ea), 1.64–1.55
a
e
(m, H-2ab); 13C NMR (D2O, 75 MHz): d 137.6, 137.3,
129.5, 129.4, 129.3, 129.1, 99.3 (C-1b), 97.4 (C-1a,
C-10), 77.1, 77.0, 75.5, 74.0, 71.9, 71.8, 71.7, 71.6, 70.2,
69.7, 68.8, 61.9, 61.4, 39.7 (C-2b), 38.0 (C-20), 37.6
(C-2a). HR-MS m/z: [M+Na]+ calcd for C19H28O9,
423.1631; found, 423.1625.
3.5. 4-Methoxybenzyl 4-O-(2-deoxy-3,4,6-tri-O-acetyl-a-
D-lyxo-hexopyranosyl)-2,3,6-tri-O-benzoyl-b-D-gluco-
pyranoside (9)
3.7. Benzyl 4-O-(2-deoxy-a-D-lyxo-hexopyranosyl)-2-
deoxy-D-arabino-hexopyranoside (11)
Compound 9 was prepared according to the method
described for the synthesis of compound 8, using 74
(0.35 g, 1.05 mmol), 3 (0.520 g, 0.95 mmol), 4 A MS
˚
Compound 11 was prepared according to the method
described for the synthesis of compound 10, using 6
(1 g), CH2Cl2 (12 mL), NIS (0.28 g, 1.26 mmol) and
TfOH (11 lL, 0.13 mmol). Purification of the crude
reaction mixture afforded disaccharide 9 (0.39 g, 52%),
as a white foamy solid. Rf = 0.18 (EtOAc/pet ether
˚
(0.28 g, 0.82 mmol), 7 (0.32 g, 0.97 mmol), 4 A MS
(0.8 g), CH2Cl2 (8 mL), NIS (0.26 g, 1.16 mmol) and
TfOH (10 lL, 0.11 mmol). Purification afforded 11
(0.21 g, 64% conversion after 2 steps, a/b = 2:1), as a
24
1:2); ½aꢂD +36.0 (c 1.7, CHCl3); 1H NMR (CDCl3,
1
300 MHz): d 8.14–7.35 (m, 15H, aromatic), 7.06 (d,
2H, J = 8.4 Hz, aromatic), 6.67 (d, 2H, J = 8.4 Hz, aro-
matic), 5.65 (app. t, 1H, J = 9.0 Hz, H-3), 5.42 (dd, 1H,
J = 7.8, 9.0 Hz, H-2), 5.27 (app. s, 1H, H-40), 5.22 (d,
1H, J = 4.5 Hz, H-10), 5.16–5.14 (m, 1H, H-30), 4.80
(app. t, 2H, J = 11.7 Hz, PhCH2), 4.69 (d, 1H,
J = 7.8 Hz, H-1), 4.59–4.53 (m, 2H, H-6a, H-6b). 4.27
(app. t, 1H, J = 6.0 Hz, H-50), 4.13 (app. t, 1H,
J = 9.0 Hz, H-4), 3.98–3.94 (m, 2H, H-60a; H-6b0 ), 3.88–
3.84 (m, 1H, H-5), 3.75 (br s, 3H, OCH3), 2.03–1.77
(band, 11H, H-20 ; COCH3; H-20 ); 13C NMR (CDCl3,
white foamy solid. Rf = 0.23 (12% MeOH/CHCl3); H
NMR (D2O, 300 MHz): d 7.27–7.24 (band, aromatic),
5.33 (br s, H-10), 5.09 (m, H-3b), 4.92 (br s, H-1a),
4.73–4.65 (band, H-30, H-40, PhCH2, H-5a, H-4b),
4.52–4.49 (m, H-6aa, H-6ba), 4.34 (app. d,
J = 10.8 Hz,
H-1b),
3.84–3.18
(band,
H-50,
H-60 ; H-60 , H-3a, H-4a, H-6ab, H-6bb, H-5b), 2.04–
a
b
1.78 (m, H-2eb, H-20 ; H-20 , H-2aa), 1.64–1.55 (m,
a
e
H-2ea), 1.45–1.34 (m, H-2ab); 13C NMR (D2O,
75 MHz): d 137.7, 137.3, 129.5, 129.4, 129.3, 129.2,
129.1, 99.5 (C-1b), 97.4 (C-1a, C-10), 77.2, 75.5, 72.6,
71.9, 70.0, 69.7, 68.3, 65.4, 62.3, 61.8, 61.3, 39.7
(C-2b), 38.0 (C-2a), 32.3 (C-20). HR-MS m/z:
[M+Na]+ calcd for C19H28O9, 423.1631; found, 423.1628.
e
a
75 MHz): d 170.4, 170.0, 169.8, 165.4, 165.2, 159.4,
148.1, 133.5, 133.3, 133.2, 129.8, 129.7, 129.2, 128.8,
128.7, 128.5, 128.3, 128.2, 128.1, 113.7, 99.4 (C-1), 98.4
(C-10), 76.1, 75.4, 72.9, 71.7, 70.0, 69.1, 68.0, 67.9,
66.2, 65.4, 63.6, 62.1, 55.1 (OCH3), 30.1 (C-20), 20.7,
20.6. HR-MS m/z: [M+Na]+ calcd for C47H48O17,
907.2789; found, 907.2762.
3.8. 2-Deoxy-a-D-arabino-hexopyranosyl-(1!4)-D-gluco-
pyranose (12)
To a solution of 8 (0.22 g, 0.25 mmol) in MeCN/H2O
(5:1, v/v, 8 mL), CAN (0.16 g, 0.3 mmol) was added
and stirred at room temperature. After 4 h, the reaction
mixture was diluted with EtOAc (30 mL), washed with
aq NaHSO3, water, dried and concentrated. The residue
was admixed with MeOH (8 mL), NaOMe (cat.) and
stirred for 6 h at room temperature, neutralized with
IR 120 resin (H+) and evaporated. The residue was puri-
fied and freeze-dried to afford 12 (0.07 g, 85%,
a/b = 36:64), as an amorphous solid. Rf = 0.18 (7:2:1
3.6. Benzyl 4-O-(2-deoxy-a-D-arabino-hexopyranosyl)-2-
deoxy-D-arabino-hexopyranoside (10)
Compound 10 was prepared according to the method
described for the synthesis of compound 8, using 4
˚
(0.38 g, 1.13 mmol), 6 (0.36 g, 1.07 mmol), 4 A MS
(0.8 g), CH2Cl2 (8 mL), NIS (0.3 g, 1.35 mmol) and
TfOH (12 lL, 0.13 mmol). After work-up and concen-
tration, the crude product was admixed with NaOMe

S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
459
24
D
EtOAc/CH3OH/H2O); ½aꢂ +50.5 (c 1, H2O); 1H NMR
H-20 ), 2.10 (d, J = 5.2, 13.6 Hz, H-2ea), 1.81–1.68 (m,
e
(D2O, 300 MHz): d 5.36 (d, 1H, J = 2.7 Hz, H-10), 5.08
(d, 1H, J = 3.6 Hz, H-1a), 4.48 (d, 1H, J = 7.8 Hz,
H-1b), 3.76–3.38 (band, 15H, H-4a, H-5a, H-6a,ba,
H-2b, H-3b, H-4b, H-5b, H-6a,bb, H-30, H-40, H-50,
H-60a;b), 3.23 (app. t, 1H, J = 9.3 Hz, H-3a), 3.10 (dd,
1H, J = 7.8, 9.3 Hz, H-2a), 2.13–2.07 (m, 1H, H-20e),
1.59 (ddd, 1H, J = 3.6, 11.7, 12.6 Hz, H-20a); 13C NMR
(D2O, 75 MHz): d 99.4 (C-10), 96.6 (C-1b), 92.6 (C-
1a), 77.2, 76.9, 75.4, 74.2, 74.0, 73.9, 72.3, 71.6, 70.8,
69.5, 68.8, 61.6, 61.5, 37.7 (C-20). HR-MS m/z:
[M+Na]+ calcd for C12H22O10, 349.1111; found,
349.1115. Anal. Calcd for C12H22O10ÆH2O: C, 41.86;
H, 6.98. Found: C, 41.76; H, 7.30.
H-2aa, H-20 ), 1.55 (ddd, J = 9.0, 10.0, 12.4 Hz, H-2ab);
a
13C NMR (D2O, 100 MHz): d 98.4 (C-10), 93.3 (C-1b),
90.9 (C-1a), 76.5, 76.0, 74.5, 73.2, 71.1, 70.8, 70.6,
68.5, 67.9, 61.7, 60.7, 60.5, 37.7 (C-2b), 36.8 (C-20),
36.4 (C-2a). HR-MS m/z: [M+Na]+ calcd for
C12H22O9, 333.1162; found, 333.1151. Anal. Calcd for
C12H22O9Æ2H2O: C, 41.62; H, 7.51. Found: C, 41.14;
H, 7.48.
3.11. 2-Deoxy-a-D-lyxo-hexopyranosyl-(1!4)-2-deoxy-
D-arabino-hexopyranose (15)
Compound 15 was prepared according to the method
described for the synthesis of compound 14, using 11
(0.21 g, 0.52 mmol), MeOH (10 mL), Pd/C (10%,
0.05 g) and H2 gas. After filtration and solvent evapora-
tion, the residue was purified and freeze-dried to obtain
15 (0.16 g, 95%, a/b = 45:55), as an amorphous solid.
3.9. 2-Deoxy-a-D-lyxo-hexopyranosyl-(1!4)-D-gluco-
pyranose (13)
Compound 13 was prepared according to the method
described for the synthesis of compound 12, using 9
(0.3 g, 0.34 mmol), CAN (0.22 g, 0.4 mmol), MeCN/
H2O (5:1, v/v, 8 mL), followed by NaOMe (cat.) in
MeOH (10 mL). After neutralization and evaporation,
the residue was purified to afford 13 (0.086 g, 78%,
24
Rf = 0.26 (7:2:1 EtOAc/CH3OH/H2O); ½aꢂD +125.8 (c
2, H2O); 1H NMR (D2O, 400 MHz): d 5.52 (br s,
H-10), 5.36 (d, J = 3.2 Hz, H-1a), 4.91 (dd, J = 1.6,
9.5 Hz, H-1b), 4.07 (ddd, J = 5.1, 9.4, 12.3 Hz, H-3a),
4.04–3.89 (band, H-5a, H-6a,ba, H-3b, H-6a,bb, H-30,
H-40, H-50, H-6a0 ;b), 3.58 (app. t, J = 9.4 Hz, H-4a),
3.49 (app. t, J = 9.5 Hz, H-4b), 3.42 (ddd, J = 2.1, 5.2,
9.7 Hz, H-5b), 2.24 (app. d, J = 4.8, 13.5 Hz, H-20e),
2.10 (app. d, J = 5.2, 12.8 Hz, H-2ea), 2.00–1.91 (m,
a/b = 36:64), as an amorphous solid. Rf = 0.16 (7:2:1
24
EtOAc/CH3OH/H2O); ½aꢂ +86.3 (c 0.9, H2O); 1H
D
NMR (D2O, 400 MHz): d 5.35 (br s, 1H, H-10), 5.05
(d, 1H, J = 3.6 Hz, H-1a), 4.49 (d, 1H, J = 8.0 Hz,
H-1b), 4.08–3.44 (band, 17H, H-2a, H-3a, H-4a, H-5a,
H-6a,ba, H-2b, H-3b, H-4b, H-5b, H-6a,bb, H-30, H-40,
H-50, H-6a0 ;b), 2.51–2.34 (m, 1H, H-20e), 1.94–1.86 (m,
H-2eb, H-20 ), 1.75 (ddd, J = 3.2, 12.3, 13.7 Hz, H-2aa),
a
1.55 (ddd, J = 9.5, 11.7, 12.8 Hz, H-2ab); 13C NMR
(D2O, 100 MHz): d 98.7 (C-10), 93.4 (C-1b), 91.1 (C-
1a), 76.7, 76.3, 74.6, 71.8, 71.1, 71.2, 70.6, 68.6, 67.6,
64.7, 61.6, 60.8, 37.8 (C-2b), 37.7 (C-2a), 31.5 (C-20).
HR-MS m/z: [M+Na]+ calcd for C12H22O9, 333.1162;
found, 333.1163. Anal. Calcd for C12H22O9Æ2H2O: C,
41.62; H, 7.51. Found: C, 41.13; H, 7.61.
1H, H-20a); C NMR (D2O, 100 MHz): d 98.9 (C-10),
13
95.8 (C-1b), 92.5 (C-1a), 76.4, 75.4, 75.2, 74.1, 73.4,
72.2, 71.9, 71.5, 70.1, 67.5, 64.6, 63.1, 61.7, 31.6 (C-20).
HR-MS m/z: [M+Na]+ calcd for C12H22O10, 349.1111;
found, 349.1128. Anal. Calcd for C12H22O10ÆH2O: C,
41.86; H, 6.98. Found: C, 41.08; H, 7.08.
3.12. Ethyl 4-O-(2,3,4,6-tetra-O-acetyl-a-D-gluco-
pyranosyl)-2-deoxy-3,6-di-O-acetyl-1-thio-D-arabino-
hexopyranoside (18)
3.10. 2-Deoxy-a-D-arabino-hexopyranosyl-(1!4)-2-
deoxy-D-arabino-hexopyranose (14)
A solution of 10 (0.28 g, 0.7 mmol) in MeOH (10 mL)
was hydrogenolyzed over Pd/C (10%, 0.05 g) at room
temperature under positive pressure of H2 for 3 days, fil-
tered through Celite pad and evaporated. The residue
was purified and freeze-dried to obtain 14 (0.2 g, 90%,
3.12.1. Method A. Compound 18 was synthesized
according to the previously described method,4 1612
(1.0 g, 1.78 mmol), CAN (0.1 g, 0.18 mmol), EtSH
(0.7 mL, 9.45 mmol) and MeCN (15 mL). The crude
product was purified to afford 18 (0.167 g, 15%,
a/b = 5:1), as a colourless syrup, along with ethyl
4-O-(2,3,4,6-tetra-O-acetyl-a-D-glucopyranosyl)-6-O-
acetyl-2,3-dideoxy-1-thio-D-erythro-hex-2-enopyranoside
(Ferrier product) 0.66 g (66% yield, a/b = 90:10).
a/b = 2:3), as an amorphous solid. Rf = 0.28 (7:2:1
24
EtOAc/CH3OH/H2O); ½aꢂ +77.5 (c 2, H2O), lit.6
D
20
1
½aꢂD +126.6 (c 0.47, H2O); H NMR (D2O, 400 MHz):
d 5.51 (br s, H-10), 5.35 (d, J = 2.8 Hz, H-1a), 4.91
(dd, J = 2.0, 10.0 Hz, H-1b), 4.08 (ddd, J = 5.2, 9.6,
12.4 Hz, H-3a), 3.88–3.72 (band, H-5a, H-6a,ba, H-3b,
H-6a,bb, H-30, H-6a0 ;b), 3.66 (ddd, J = 2.2, 5.1, 9.5 Hz,
H-50), 3.56 (app. t, J = 9.6 Hz, H-4a), 3.50 (app. t,
J = 9.6 Hz, H-4b), 3.43 (ddd, J = 2.0, 5.4, 9.7 Hz,
H-5b), 3.38 (app. t, J = 9.7 Hz, H-40), 2.25 (m, H-2eb,
3.12.2. Method B. To a solution of 20 (0.61 g,
0.9 mmol) and EtSH (0.4 mL, 0.54 mmol) in CH2Cl2
(7 mL), BF3–Et2O was added at ꢁ40 °C. The reaction
mixture was allowed to come to room temperature over
a 4 h period of time, quenched with Et3N, concentrated

460
S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
and purified to afford 18 (0.47 g, 76%, a/b = 6:1), as a
colourless syrup. Rf = 0.46 (1:1 EtOAc/pet ether); H
(2.2 mL), a catalytic amount of HBr/AcOH (33%, w/v,
206 lL, 0.94 mmol) and CH2Cl2 (13 mL). The crude
reaction mixture was purified to afford 20 (2.34 g,
91%, a/b = 96:4), as a colourless gum. Rf = 0.41 (1:1
1
NMR (CDCl3, 300 MHz): d 5.57 (d, J = 4.0 Hz, H-10),
5.43–5.37 (m, H-40, H-1), 5.16–4.85 (band, H-3, H-30,
H-20), 4.38–3.84 (band, H-6a0 ; H-60b, H-50, H-4, H-5,
H-6a, H-6b), 2.68–2.49 (m, SCH2), 2.18–1.81 (band,
H-2e, H-2a, CH3CO), 1.30 (t, J = 7.8 Hz, CH3); charac-
teristic resonances for b-anomer found: 4.64 (dd,
J = 2.4, 10.0 Hz, H-1), 3.70–3.67 (m, H-5); 13C NMR
(CDCl3, 75 MHz): d 170.6, 170.5, 170.3, 169.9, 169.8,
169.4, 95.4 (C-10), 79.1 (C-1), 73.5, 72.9, 70.0, 69.4,
68.2, 67.9, 63.3, 61.4, 34.7 (C-2), 24.7 (SCH2), 21.1,
20.8, 20.7, 20.6, 20.5, 20.4, 20.3, 14.6. HR-MS
m/z: [M+Na]+ calcd for C26H38O15S, 645.1829; found,
645.1833.
1
EtOAc/pet ether); H NMR (CDCl3, 300 MHz) d 6.19
(d, 1H, J = 2.4 Hz, H-1), 5.60 (d, 1H, J = 4.0 Hz,
H-10), 5.40 (app. t, 1H, J = 10.0 Hz, H-40), 5.20 (ddd,
1H, J = 5.4, 8.4, 11.4 Hz, H-3), 5.09 (app. t, 1H,
J = 10.0 Hz, H-30), 4.89 (dd, 1H, J = 4.0, 10.0 Hz,
H-20), 4.38–4.23 (m, 4H, H-4, H-5, H-6a0 ; H-6b0 ), 4.08–
3.88 (m, 3H, H-50, H-6a, H-6b), 2.29 (app. dd, 1H,
J = 5.4, 12.3 Hz, H-2e), 2.16–2.02 (band, 21H, CH3CO),
1.75 (ddd, 1H, J = 2.4, 11.4, 12.3 Hz, H-2a); characteris-
tic resonances for the b-anomer: d 5.80 (dd, 1H, J = 2.0,
9.9 Hz, H-1), 3.86–3.85 (m, 1H, H-5); 13C NMR
(CDCl3, 75 MHz) d 170.5, 170.4, 170.2, 170.0, 169.9,
169.3, 169.0, 95.6 (C-10), 90.4 (C-1), 72.6, 72.0, 70.1,
70.0, 69.3, 68.3, 67.8, 62.9, 61.3, 33.4 (C-2), 21.1, 21.0,
20.7, 20.6, 20.5, 20.4. HR-MS m/z: [M+Na]+ calcd for
C26H36O17, 643.1850; found, 643.1863.
3.13. Ethyl 4-O-(2,3,4,6-tetra-O-acetyl-b-D-galacto-
pyranosyl)-2-deoxy-3,6-di-O-acetyl-1-thio-D-arabino-
hexopyranoside (19)
3.13.1. Method A. Compound 19 was synthesized
according to the previously described method,4 using
1712 (1.37 g, 2.46 mmol), CAN (0.14 g, 0.24 mmol),
EtSH (1.0 mL, 0.01 mol) and MeCN (20 mL). The crude
product was purified to afford 19 (0.152 g, 11%, a/b =
5:1), as a white foamy solid, as well as ethyl 4-O(2,
3,4,6-tetra-O-acetyl-b-D-galactopyranosyl)-6-O-acetyl-
2,3-dideoxy-1-thio-D-erythro-hex-2-enopyranoside (Fer-
rier product) 0.977 g (71% yield, a/b = 3:2).
3.15. 4-O-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyranosyl)-
2-deoxy-1,3,6-tri-O-acetyl-D-arabino-hexopyranoside
(21)
Compound 21 was synthesized by a known procedure,13
using 1712 (8.10 g, 0.01 mol), Ac2O (13.2 mL), AcOH
(7.3 mL), a catalytic amount of HBr/AcOH (33%, w/v,
0.7 mL, 2.85 mmol) and CH2Cl2 (42 mL). The crude
reaction mixture was purified to afford 21 (8.18 g,
84%, a/b = 95:5), as a white foam. Rf = 0.12 (1:1
3.13.2. Method B. To a solution of 21 (1.11 g,
1.79 mmol) and EtSH (0.7 mL, 9.45 mmol) in CH2Cl2
(12 mL), BF3–Et2O was added at ꢁ40 °C. The reaction
mixture was allowed to come to room temperature over
a 4 h period of time, quenched with Et3N, concentrated
and purified to afford 19 (0.902 g, 81% yield, a/b = 5:1),
as a white foamy solid. Rf = 0.41 (1:1 EtOAc/pet ether);
1H NMR (CDCl3, 400 MHz): d 5.35–5.32 (m, H-30,
H-1), 5.20–5.10 (band, H-3, H-40), 4.99–4.97 (m, H-20),
4.55–4.52 (m, H-10, H-50), 4.30–4.22 (m, H-4, H-5),
4.18–3.85 (band, H-60 ; H-60 , H-6a, H-6b), 2.70–2.48
1
EtOAc/pet ether); H NMR (CDCl3, 400 MHz) d 6.09
(d, 1H, J = 1.6 Hz, H-1), 5.29–5.27 (m, 2H, H-3,
H-40), 5.07–5.05 (m, 1H, H-20), 4.89 (dd, 1H, J = 3.6,
10.8 Hz, H-30), 4.49 (d, 1H, J = 8.0 Hz, H-10), 4.30–
4.27 (m, 0 1H, H-6b), 4.09–3.97 (m, 3H, H-6a,
H-60a; H-6b), 3.90–3.79 (m, 2H, H-50, H-5), 3.68–3.66
(m, 1H, H-4), 2.22 (app. dd, 1H, J = 5.0, 12.8 Hz,
H-2e), 2.08–1.98 (band, 21H, CH3CO), 1.89–1.72 (m,
1H, H-2a); characteristic resonances for the b-anomer:
d 5.89 (dd, 1H, J = 2.0, 9.9 Hz, H-1), 3.58–3.55 (m,
1H, H-5); 13C NMR (CDCl3, 100 MHz) d 170.6,
170.5, 170.4, 170.2, 170.1, 169.7, 169.3, 101.2 (C-10),
90.6 (C-1), 71.8, 70.8, 70.7, 70.6, 69.1, 68.9, 67.4, 62.9,
62.3, 33.4 (C-2), 21.2, 21.1, 21.0, 20.9, 20.7, 20.6. HR-
MS m/z: [M+Na]+ calcd for C26H36O17, 643.1850;
found, 643.1840.
a
b
(m, SCH2), 2.18–1.81 (band, H-2a, H-2e, CH3CO),
1.26 (t, J = 7.8 Hz, CH3); characteristic resonances for
b-anomer found: 4.79 (app. d, J = 10.0 Hz, H-1), 3.62–
3.60 (m, H-5); 13C NMR (CDCl3, 100 MHz): d 170.5,
170.4, 170.2, 169.8, 169.6, 169.2, 101.1 (C-10), 79.2
(C-1), 72.3, 70.5, 69.1, 68.7, 66.7, 63.0, 62.2, 60.9, 34.7
(C-2), 24.8 (SCH2), 21.1, 21.0, 20.9, 20.8, 20.7, 20.5,
14.5. HR-MS m/z: [M+Na]+ calcd for C26H38O15S,
645.1829; found, 645.1821.
3.16. a-D-Glucopyranosyl-(1!4)-2-deoxy-D-arabino-
hexopyranose (22)
3.14. 4-O-(2,3,4,6-Tetra-O-acetyl-a-D-glucopyranosyl)-2-
deoxy-1,3,6-tri-O-acetyl-D-arabino-hexopyranoside (20)
3.16.1. Method A. To a solution of 18 (0.17 g,
0.27 mmol) in CH2Cl2 (5 mL), NBS (0.06 g, 0.32 mmol)
and acetone/H2O (9:1 v/v, 8 mL) was added. After
5 min, the reaction mixture was diluted with CH2Cl2
(25 mL), washed with aq Na2S2O3, water, dried and
Compound 20 was synthesized by a known procedure,13
using 1612 (2.35 g, 4.22 mmol), Ac2O (4 mL), AcOH

S. Paul, N. Jayaraman / Carbohydrate Research 343 (2008) 453–461
461
concentrated. The residue was dissolved in MeOH, trea-
Acknowledgements
ted with NaOMe (cat.) at room temperature for 6 h,
neutralized with IR-120 resin (H+) and evaporated.
The resulting residue was purified and freeze-dried to
afford 22 (0.07 g, 80%), as an amorphous solid.
We are grateful to the Department of Science and Tech-
nology, New Delhi, for a financial support. S.P. thanks
the Council of Scientific and Industrial Research, New
Delhi, for a research fellowship.
3.16.2. Method B. Alternatively, 22 was obtained by
treating 20 (0.5 g, 0.91 mmol) with NaOMe (cat.) in
MeOH (10 mL) for 6 h, neutralized with IR-120 resin
(H+), solvents were evaporated and residue purified to
afford 22 (0.23 g, 88%, a/b = 3:2), as an amorphous so-
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24
lid. Rf = 0.36 (6:2:1 EtOAc/CH3OH/H2O); ½aꢂD +147.4
20
D
20
(c 2, H2O), lit.6 ½aꢂ +126 (c 0.14, H2O), lit.11a ½aꢂD
20
+30.4 (H2O), lit.14b ½aꢂD +136 (H2O); H NMR (D2O,
400 MHz): d 5.30 (br s, 1H, H-10), 5.04 (d, 1H,
J = 3.3 Hz, H-1a), 4.88 (app. d, 1H, J = 9.6 Hz,
H-1b), 4.30 (ddd, 1H, J = 5.4, 9.8, 11.4 Hz, H-3a),
3.91–3.19 (band, 15H, H-4a, H-5a, H-6a,ba, H-3b, H-
4b, H-5b, H-6a,bb, H-20, H-30, H-40, H-50, H-60a;b),
2.10–2.06 (m, 1H, H-2eb), 1.96–1.92 (m, 1H, H-2ea),
1.65–1.57 (m, 1H, H-2aa), 1.45–1.34 (m, 1H, H-2ab);
13C NMR (D2O, 75 MHz): d 95.4 (C-10), 94.5 (C-1b),
92.2 (C-1a), 76.0, 75.8, 74.8, 74.2, 73.5, 70.5, 70.0,
69.5, 68.12, 65.3, 61.1, 60.7, 60.3, 34.9 (C-2a, 2b). HR-
MS m/z: [M+Na]+ calcd for C12H22O10, 349.1111;
found, 349.1104. Anal. Calcd for C12H22O10ÆH2O: C,
41.86; H, 6.98. Found: C, 41.25; H, 7.34.
1
3. (a) Marzabadi, C. H.; Franck, R. W. Tetrahedron 2000,
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56, 8385–8417; (b) Veyrieres, A. In Carbohydrates in
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pound 22 using 19 (0.15 g, 0.24 mmol), NBS (0.05 g,
0.29 mmol), and acetone/H2O (9:1 v/v, 8 mL), followed
by NaOMe catalyzed deprotection of acetate group and
purification which afforded 23 (0.06 g, 75% yield), as an
amorphous solid.
5. Paul, S.; Jayaraman, N. Carbohydr. Res. 2007, 342, 1305–
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3.17.2. Method B. Similarly, 23 was also obtained
(0.174 g, 83% yield, a/b = 1:1) on treatment of 21
´
(0.4 g, 0.54 mmol) under Zemplen condition. Rf = 0.4
24
(5:4:1 EtOAc/CH3OH/H2O); ½aꢂD +33.6 (c 1.3, H2O);
1H NMR (D2O, 400 MHz): d 5.39 (d, 1H, J = 5.2 Hz,
H-1a), 4.33–4.31 (m, 2H, H-1b, H-10), 4.11–4.07 (m, 1H,
H-3a), 4.00–3.22 (band, 15H, H-4a, H-5a, H-6a,ba, H-
3b, H-4b, H-5b, H-6a,bb, H-20, H-30, H-40, H-50,
H-60a;b), 2.11–2.07 (m, 1H, H-2eb), 1.95–1.90 (m, 2H,
H-2ea, H-2aa), 1.55–1.52 (m, 1H, H-2ab); 13C NMR
(D2O, 100 MHz): d 102.9 (C-10), 98.0 (C-1b), 93.1 (C-
1a), 79.9, 79.5, 79.3, 78.6, 75.3, 72.5, 70.9, 70.4, 68.4,
67.7, 60.9, 60.4, 60.0, 35.6 (C-2b), 33.2 (C-2a). HR-MS
m/z: [M+Na]+ calcd for C12H22O10, 349.1111; found,
349.1118. Anal. Calcd for C12H22O10ÆH2O: C, 41.86;
H, 6.98. Found: C, 41.27; H, 7.48.