A concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and 2-acetamido-2-deoxy-d-mannopyranosides

Article abstract of DOI:10.1016/j.carres.2004.11.002

4-Nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-α- and β-d-mannopyranosides were prepared from methyl 4,6-O-benzylidene-α-d- glucopyranoside and 1,3,4,6-tetra-O-acetyl-α-d-glucopyranose, respectively. Chemoselective reduction of both azides with hydrogen sulfide readily afforded 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-α-d- and -β-d-mannopyranosides in higher yields than reduction with triphenylphosphine or a polymer-supported triarylphosphine. Subsequent de-O-acetylation yielded 4-nitrophenyl 2-acetamido-2-deoxy-α-d- mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-β-d-mannopyranoside in 20% and 44% overall yields, respectively.

Full text of DOI:10.1016/j.carres.2004.11.002

Carbohydrate
RESEARCH
Carbohydrate Research 340 (2005) 161–166
Note
A concise synthesis of 4-nitrophenyl 2-azido-2-deoxy- and
2-acetamido-2-deoxy-D-mannopyranosides
*
´ ´ˇ ´ ´
Alena Popelova, Karel Kefurt, Martina Hlavackova and Jitka Moravcova
´
Department of Chemistry of Natural Compounds, Institute of Chemical Technology, Technicka 5, 166 28 Prague, Czech Republic
Received 18 June 2004; received in revised form 4 October 2004; accepted 5 November 2004
Available online 30 November 2004
Abstract—4-Nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-a- and b-D-mannopyranosides were prepared from methyl 4,6-O-benz-
ylidene-a-D-glucopyranoside and 1,3,4,6-tetra-O-acetyl-a-D-glucopyranose, respectively. Chemoselective reduction of both azides
with hydrogen sulfide readily afforded 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-a-D- and -b-D-mannopyranosides in
higher yields than reduction with triphenylphosphine or a polymer-supported triarylphosphine. Subsequent de-O-acetylation
yielded 4-nitrophenyl 2-acetamido-2-deoxy-a-D-mannopyranoside and 4-nitrophenyl 2-acetamido-2-deoxy-b-D-mannopyranoside
in 20% and 44% overall yields, respectively.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Keywords: 2-Azido-2-deoxymannoside; 2-Acetamido-2-deoxymannopyranoside; 4-Nitrophenyl glycoside; Migration of acetyl group
2-Acetamido-2-deoxy-D-mannopyranose (ManNAc) unis
are integral parts of a number of bacterial polysaccha-
rides and lipopolysaccharides.1–4 Recently, ManNAc
was identified as a strong ligand5 for the natural killer
cell activating protein NKR-P1 and it is, inter alia, an
intermediate in the biosynthesis of N-acetyl D-neurami-
nic acid.6 The ManNAc repeating unit has been identi-
fied in bacterial polysaccharides7 and oligosaccharides
containing ManNAc were found to possess immunosti-
mulation activity.8 Moreover, mannose-binding lectin,
a pattern recognition molecule of the innate immune sys-
tem, was proved to interact with a range of sugars includ-
ing ManNAc.9 The stereoselective introduction of the
ManNAc moiety into an oligosaccharide chain still rep-
resents a crucial step in the preparation of potential car-
bohydrate-based therapeutics.10 Generally, a variety of
4-nitrophenyl D-hexopyranosides has been exploited as
efficient chromogenic glycosyl donors for chemoenzymic
synthesis of oligosaccharides. In contrast, both 4-nitro-
phenyl 2-acetamido-2-deoxy-a-mannopyranoside (1)
and 4-nitrophenyl 2-acetamido-2-deoxy-b-D-mannopyr-
anoside (2) have not yet been utilized as enzyme sub-
strates although their syntheses were already described.
Glycoside 1 was prepared in 2% yield from 2-acetam-
ido-2-deoxy-D-glucose 30 years ago.11 A synthesis of 2
from 4-nitrophenyl b-D-glucopyranoside via 4-nitrophe-
nyl 3-O-benzoyl-4,6-benzylidene-b-D-glucopyranoside12
was published only in 2003.13 Nevertheless, the laborious
pathway with 10 steps prevents a gram scale application.
We now wish to report our synthetic strategy in this
area that follows the idea of respective 2-azido-2-deoxy
precursors.14 This permits us to start from D-glucose
taking advantage of SN2 inversion of the configuration
at the C-2 atom.
Initially, we attempted to synthesize 4-nitrophenyl
3,4,6-tri-O-acetyl-2-azido-2-deoxy-a-D-mannopyranosi-
de (3) from 1,3,4,6-tetra-O-acetyl-a-D-glucopyranose (4)
that is readily available by a one-pot reaction starting
from D-glucose.15 Tetra-O-acetate 4 was isolated by a
simple crystallization in 25% yield and it was coupled
with trifluoromethanesulfonic anhydride to give 1,3,4,6-
tetra-O-acetyl-2-O-trifluoromethanesulfonyl-a-D-gluco-
pyranose (5) in 66% yield. Compound 5 was then
subjected to the attack of sodium azide16 but all attempts
to prepare 1,3,4,6-tetra-O-acetyl-2-azido-2-deoxy-a-D-
mannopyranose (6) in a yield higher than 10% failed
*
Corresponding author. Tel.: +420 220 444 283; fax: +420 224 310
859; e-mail: jitka.moravcova@vscht.cz
0008-6215/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.11.002

´
A. Popelova et al. / Carbohydrate Research 340 (2005) 161–166
162
(Scheme 1).16 In subsequent approach (Scheme 1),
treatment of commercially available methyl 4,6-O-benzy-
lidene-a-D-glucopyranoside (7) with trifluoromethane-
sulfonic anhydride gave methyl 4,6-O-benzylidene-2-O-
trifluoromethanesulfonyl-a-D-glucopyranoside (8).17 In
our hands, the reported yield17 of selective monotriflation
was not reproducible. Under optimized conditions, we
were able to obtain 2-O-triflate 8 in the yield of 50% only
if trifluoromethanesulfonic anhydride diluted with
dichloromethane was slowly added to a solution of 7
at 3ꢁC. In addition to 8, resulting mixture contained
small amount of methyl 4,6-O-benzylidene-2,3-di-O-
trifluoromethanesulfonyl-a-D-glucopyranoside whereas
about 35% of the starting glucoside 7 was recovered. In
contrast to the paper,18 azidation of 8 was accelerated
by heating and methyl 2-azido-4,6-O-benzylidene-2-
deoxy-a-D-mannopyranoside (9) was prepared in 95%
yield within 4.5h at 70ꢁC instead of 3d at room temper-
ature. Acetolysis of 9 gave tetra-O-acetate 6 in 75% yield
and, finally, stereoselective glycosylation was performed
directly without any activation step by melting of tetra-
O-acetate 6 with 4-nitrophenol in the presence of anhy-
drous zinc chloride.19 a-Mannopyranoside 3 was the only
product formed (70% yield) thus giving the overall yield
´
of 25% from 7. Zemplen deacetylation of 3 afforded 4-
nitrophenyl 2-azido-2-deoxy-a-D-mannopyranoside (10).
For the synthesis of the target 4-nitrophenyl 3,4,6-
tri-O-acetyl-2-azido-2-deoxy-b-D-mannopyranoside (11)
(Scheme 2), 1,3,4,6-tetra-O-acetyl-a-D-glucopyranose
(4) was converted into 3,4,6-tri-O-acetyl-a-D-glucopyr-
anosyl bromide (12) according to the procedure
described for 3,4,6-tri-O-acetyl-a-D-galactopyranosyl
bromide.20 Pure bromide 12 was obtained in 65% yield
after purification by flash chromatography on silica gel
and characterized by 1H NMR spectral data, which were
in accord with those published.21 The relative instability
of 12 necessitated immediate reaction of the crude 12
with 4-nitrophenol in the presence of potassium
carbonate.20 These conditions stereoselectively afforded
4-nitrophenyl
3,4,6-tri-O-acetyl-b-D-glucopyranoside
(13) in 78% overall yield after column chromatography.
This procedure was less time-consuming than that de-
scribed22 for 3,4,6-tri-O-acetyl-a-D-glucopyranosyl chlo-
ride and sodium 4-nitrophenoxide apart from a slightly
higher yield of 13. Then, the activation of the 2-OH
group in glucoside 13 was carried out by esterification
N3
AcO
O
h
AcO
AcO
10
D
-Glucose
a
3
OpNP
d
N3
AcO
AcO
O
AcO
AcO
AcO
AcO
O
O
b
c
AcO
AcO
AcO
HO
TfO
OAc
4
5
8
OAc
6
9
OAc
g
N3
Ph
O
Ph
Ph
O
O
O
O
O
f
O
e
O
O
HO
HO
HO
HO
TfO
OMe
7
OMe
OMe
Scheme 1. Reagents and conditions: (a) (1) Ac2O, HClO4, rt, 1h, (2) PBr3, H2O, rt, 1.5h, (3) NaOAc, rt, 2h 25%; (b) Tf2O, py, CH2Cl2, 3ꢁC, then rt,
1.5h, 66%; (c) NaN3, DMF, 60ꢁC, 5h, 10%; (d) p-NPOH, ZnCl2, 120ꢁC, reduced pressure, 25min, 70%; (e) Tf2O, py, CH2Cl2, 3ꢁC, 1.5h, 50%;
(f) NaN3, DMF, 70ꢁC, 4.5h, 95%; (g) 3% H2SO4 in Ac2O, rt, 35min, 75%; (h) MeONa, MeOH, rt, 20min, 94%.
AcO
AcO
AcO
AcO
AcO
AcO
O
O
O
a
b
c
OpNP
AcO
AcO
AcO
HO
HO
HO
13
12
4
Br
OAc
N3
AcO
AcO
AcO
O
O
e
AcO
d
OpNP
OpNP
15
AcO
AcO
TfO
14
11
Scheme 2. Reagents and conditions: (a) HBr, CH2Cl2, 3ꢁC, 3h; (b) p-NPOH, K2CO3, acetone, rt, 16h, 78% from 4; (c) Tf2O, py, CH2Cl2, 3ꢁC, then
rt, 1.5h, 84%; (d) NaN3, DMF, rt, 18h, 84%; (e) MeONa, MeOH, rt, 20min, 96%.

´
A. Popelova et al. / Carbohydrate Research 340 (2005) 161–166
163
with trifluoromethanesulfonic anhydride in a dichloro-
methane-pyridine mixture.23 Pure 4-nitrophenyl 3,4,6-
tri-O-acetyl-2-O-trifluoromethanesulfonyl-b-D-glucopyr-
anoside (14) was isolated in 84% yield after column
chromatography. The use of a crude glucoside 14 in
the subsequent nucleophilic displacement with sodium
In conclusion, a combination of nucleophilic substitu-
tion and glycosylation represents an easy synthetic route
to 4-nitrophenyl 2-azido-2-deoxy-D-mannopyranosides
in a gram scale and high-overall yield. Subsequent selec-
tive reduction with hydrogen sulfide readily provides
respective 4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-D-
mannopyranosides. These selectively protected com-
pounds could be useful tool for N-acetyl mannos-
amine-containing oligosaccharides synthesis.
azide afforded 4-nitrophenyl 3,4,6-tri-O-acetyl-2-azido-
20
2-deoxy-b-D-mannopyranoside (11) in 84% yield (½aꢀ
D
´
ꢁ117.6 (c 0.9, CHCl3); IR: 2116 (N3)). Zemplen deacet-
ylation of 11 lead to 4-nitrophenyl 2-azido-2-deoxy-b-D-
mannopyranoside (15, mp 116–118ꢁC (CHCl3–MeOH);
20
D
1
½aꢀ ꢁ1.7 (c 1.0, EtOH); IR: 2119 (N3)). H and 13C
1. Experimental
NMR data for 15 (CD3OD) and 11 were in agreement
with those published.13
1.1. General methods
For the chemoselective reduction of an azido group in
the presence of nitro group, a triphenylphosphine–water
system was tested first.13,24,25 Thus, the azido group in
both mannosides 3 and 11 was smoothly reduced
(Scheme 3) affording a single product identified as
4-nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-a-D-
mannopyranoside (16) and 4-nitrophenyl 2-acetamido-
4,6-di-O-acetyl-2-deoxy-b-D-mannopyranoside (17), res-
pectively. The exclusive formation of the acetami-
do compounds 16 and 17 bearing free 3-OH group could
result from O-3 ! N-2 acetyl migration; to our knowl-
edge, this is the first example of acetyl transfer observed
under conditions of the Staudinger reaction. A deeper
mechanistic study forms a part of our ongoing work in
this area. The isolated yield of mannosides 16 and 17
was only 65% although almost quantitative conversion
was achieved. The purification of the desired product
in particular from triphenylphosphine oxide was
tedious. To avoid this problem, we replaced triphenyl-
phosphine by a commercially available polystyryl diphe-
nylphosphine resin but the reduction of 3 in dioxane
proceeded slowly, providing 16 in a modest yield after
5 days. Considering the preparative limitation of this
reduction method, the use of hydrogen sulfide26 as alter-
native reducing agent was next investigated. In this way
both azides 3 and 11 were efficiently reduced to manno-
sides 16 and 17, respectively, in 86% yield after a simple
chromatographic separation. Compounds 16 and 17
Optical rotations were measured on a Jasco Model DIP-
370 polarimeter and are given in 10ꢁ1 degcm2 gꢁ1. Melt-
ing points were determined with a Kofler hot block and
are uncorrected. NMR spectra were recorded on a Bruker
Avance DRX-500 (500.1MHz for 1H, 125.7MHz for
13C) at 25ꢁC in CDCl3 solution unless otherwise speci-
fied. Chemical shifts are expressed in parts per million
downfield from Me4Si. Assignments of 13C and 1H signals
are based on APT, HMQC and COSY experiments. IR
spectra (wave numbers in cmꢁ1) were measured on a
FT IR Nicolet 740 spectrometer in CHCl3 solutions or
KBr pellets. MS spectra of MeOH solution were recorded
on a Q-TOF Micro spectrometer (Waters-Micromass)
with electrospray ionization in positive mode. Elemen-
tary analysis was performed on CHN-Perkin–Elmer-
2400. Reactions were followed on TLC on silica gel
(10–40lm, Merck) and column chromatography was car-
ried out on silica gel (100–160lm, Merck). Compounds
on TLC plates were visualized by spraying with 1%
cerium(IV)sulfate in 10% sulfuric acid and subsequent
mineralization or iodine vapors were used for monitoring
of triphenylphosphine oxide. All solvents were dried
prior to distillation and stored over molecular sieves. Sol-
vents were removed under reduced pressure below 45ꢁC.
1.2. 1,3,4,6-Tetra-O-acetyl-2-O-trifluoromethanesulfonyl-
a-D-glucopyranose (5)
´
were finally de-O-acetylated using the Zemplen proce-
dure to afford expected glycosides 1 (mp 130–131ꢁC
Triflic anhydride (1.1mL, 6.75mmol) was slowly added
to a stirred soln of 1,3,4,6-tetra-O-acetyl-a-D-glucopyra-
nose (4)15 (1.96g, 5.62mmol) in 1:2 pyridine–dichlorome-
thane mixture (60mL) at 3ꢁC. After 1.5h the reaction was
complete, the reaction mixture was concentrated under
20
(H2O); ½aꢀ +60.9 (c 1.0, EtOH)) and 2 (mp 108–
D
20
110ꢁC (EtOH), ½aꢀ ꢁ93.3 (c 0.9, MeOH)) in almost
D
1
quantitative yields. H and 13C NMR data (D2O) of 1
and 2 were in agreement with those published.13
N3
O
NHAc
O
NHAc
O
AcO
AcO
AcO
AcO
HO
HO
R2
R2
R2
b
a
HO
HO
AcO
R1
R1
R1
R1 = OpNP, R2 = H
11 R1 = H, R2 = OpNP
1 R1 = OpNP, R2 = H
16 R1 = OpNP, R2 = H
17 R1 = H, R2 = OpNP
3
2 R1 = H, R2 = OpNP
Scheme 3. Reagents and conditions: (a) H2S, py, water, rt, 3.5h; 86%; (b) MeONa, MeOH, rt, 20min, 93%.

´
A. Popelova et al. / Carbohydrate Research 340 (2005) 161–166
164
reduced pressure and the residue was evaporated twice
with toluene. Purification on silica gel (3:1 petroleum
ether–ethyl acetate) afforded 5 (1.79g, 66%); mp 86–
pressure. Freshly fused ZnCl2 (0.60g, 3.61mmol) was
added to the liquid mixture and heating was continued
under reduced pressure for 25min. Brown mass was
then diluted with CHCl3 under reflux, silica gel was
added and solvent was slowly evaporated. Coated silica
gel was then put on a top of column and elution with 4:1
petroleum ether–ethyl acetate yielded compound 3
20
87ꢁC (diethyl ether); ½aꢀ +99.6 (c 1.0, CHCl3); TLC
D
1
(1:1 petroleum ether–ethyl acetate): Rf 0.81. H NMR:
d 6.47 (d, 1H, J1,2 3.6Hz, H-1), 5.58 (dd, J2,3 9.8Hz, J3,4
9.8Hz, 1H, H-3), 5.16 (dd, 1H, J4,5 9.8Hz, H-4), 4.93
(dd, 1H, H-2), 4.31 (dd, 1H, J5,6b 3.7, J6a,6b 12.5Hz, H-
6b), 4.13–4.12 (m, 1H, H-5), 4.09 (dd, 1H, J6a,5 8.2Hz,
H-6a), 2.30 (s, 3H, CH3CO), 2.09 (s, 6H, CH3CO), 2.05
(s, 3H, CH3CO); 13C NMR: d 170.41, 169.65, 169.22,
168.97 (4 · CH3CO), 118.28 (q, JC,F 319.5Hz, CF3),
88.05 (C-1), 79.48 (C-2), 69.66 (C-5), 69.07 (C-3), 67.64
(C-4), 60.97 (C-6), 20.58, 20.56, 20.41, 20.30 (4 ·
CH3CO). Anal. Calcd for C15H19F3O12S: C, 37.51; H,
3.99; S, 6.67. Found: C, 37.62; H, 4.08; S, 6.48.
(0.50g, 1.11mmol, 70%); mp 131–132ꢁC (CHCl3–petro-
20
leum ether); ½aꢀ +113.5 (c 1.2, CHCl3); IR: 2115 (N3).
D
1H NMR and 13C NMR spectra were in agreement
with those published.13
1.7. 4-Nitrophenyl 2-azido-2-deoxy-a-D-mannopyranoside
(10)
Compound 3 (122mg, 0.27mmol) was deacetylated in
MeOH (3mL) with MeONa (0.1M, 1mL). After stirring
at rt for 20min, the mixture was neutralized with AcOH
1.3. Methyl 4,6-O-benzylidene-2-O-trifluoro-
methanesulfonyl-a-D-glucopyranoside (8)
and concentrated. Flash chromatography of the residue
afforded 10 (83mg, 94%); mp 105–107ꢁC (EtOH), ½aꢀ
20
D
1H NMR data for 8 were in agreement with those pub-
lished;17 13C NMR: d 136.58 (quaternary C-arom),
129.49 (2C-arom), 128.43 (2C-arom), 126.22 (C-arom),
118.45 (q, JC,F 319.6Hz, CF3), 102.15 (C-acetal), 97.57
(C-1), 84.01 (C-2), 81.04 (C-4), 68.60 (C-6), 68.19
(C-3), 61.95 (C-5), 55.87 (OCH3).
+84.6 (c 0.8, EtOH). H NMR (CD3OD): d 8.23 (d,
1
2H, J 9.1Hz, H-arom), 7.21 (d, 2H, H-arom), 5.54 (d,
1H, J1,2 < 1Hz, H-1), 4.15 (dd, 1H, J2,3 3.4Hz, H-2),
3.90 (dd, 1H, J5,6b 1.3Hz, J6a,6b 12.0Hz, H-6b), 3.78
(dd, 1H, J3,4 9.2Hz, H-3), 3.69 (dd, 1H, J6a,5 5.3Hz,
H-6a), 3.55 (dd, J4,5 9.4Hz, 1H, H-4), 3.45 (m, 1H, H-
5); 13C NMR (CD3OD): d 126.5 (2C, C-arom), 117.2
(2C, C-arom), 98.0 (C-1), 78.8 (C-5), 73.7 (C-3), 67.9
(C-4), 66.4 (C-2), 62.1 (C-6). Anal. Calcd for
C12H14N4O7: C, 44.18; H, 4.33; N, 17.17. Found: C,
43.81; H, 4.60; N, 17.35.
1.4. Methyl 2-azido-4,6-O-benzylidene-2-deoxy-a-D-
mannopyranoside (9)
1H NMR data for 9 were in agreement with those pub-
lished;17 13C NMR: d 137.06 (quaternary C-arom),
129.31 (C-arom), 128.37 (2C-arom), 126.24 (2C-arom),
102.28 (C-acetal), 100.07 (C-1), 79.00 (C-4), 68.90 (C-
3), 68.66 (C-6), 63.63 (C-2), 63.29 (C-5), 55.17 (OCH3).
1.8. 4-Nitrophenyl 2-acetamido-4,6-di-O-acetyl-2-deoxy-
a-D-mannopyranoside (16)
Compound 3 (161mg, 0.356mmol) was dissolved in 1:1
pyridine–water mixture (10mL) and H2S was bubbled
through the solution for 5min. The mixture was left at
rt for 3.5h, then the solvents were evaporated. Column
1.5. 1,3,4,6-Tetra-O-acetyl-2-azido-2-deoxy-a-D-manno-
pyranose (6)
A
solution of methyl 2-azido-4,6-O-benzylidene-2-
chromatography (toluene–ethyl acetate 2:1) of the resi-
20
D
deoxy-a-D-mannopyranoside (9) (2.50g, 8.06mmol) in
the sulfuric acid-Ac2O mixture (48mL, 3% v/v) was stir-
red at rt for 40min. Then, the reaction mixture was di-
luted with satd aq NaHCO3-soln and ethyl acetate.
The organic layer was washed with water, dried
(MgSO4) and concentrated. The residue was purified
due afforded 16 (131mg, 0.307mmol, 86%); ½aꢀ +49.3
1
(c 1.2, CHCl3). H NMR: d 8.15 (d, 2H, J 9.2Hz, H-
arom), 7.10 (d, 2H, H-arom), 6.02 (d, 1H, JN,2 7.3Hz,
NHCOCH3), 5.64 (d, 1H, J1,2 1.2Hz, H-1), 4.94 (dd,
1H, J3,4 10.0Hz, J4,5 10.0Hz, H-4), 4.58 (m, 1H, H-2),
4.34 (dd, 1H, J3,2 5.0Hz, H-3), 4.20 (dd, 1H, J6b,5
5.1Hz, J6a,6b 12.3Hz, H-6b), 3.96 (dd, 1H, J6a,5 2.0Hz,
H-6a), 3.86 (m, 1H, H-5), 2.94 (br s, 1H, OH), 2.07 (s,
3H, COCH3), 2.05 (s, 3H, COCH3), 1.95 (s, 3H,
COCH3); 13C NMR (CD3OD): d 171.90, 170.93
(2 · CH3CO), 160.37 (quaternary C-arom), 143.00 (qua-
ternary C-arom), 125.81 (2C, C-arom), 116.38 (2C, C-
arom), 96.69 (C-1), 69.14 (C-5), 68.90 (C-4), 67.91 (C-
3), 62.12 (C-6), 52.92 (C-2), 23.34, 20.87, 20.68 (3 · C3
CO). Anal. Calcd for C18H22N2O10: C, 50.71; H, 5.20;
N, 6.57. Found: C, 50.99; H, 5.01; N, 6.38.
by column chromatography (3:1 petroleum ether–ethyl
20
acetate) to afford 6 (2.27g, 6.05mmol, 75%); ½aꢀ
D
+61.8 (c 1.1, CHCl3). H and 13C NMR data were in
1
agreement with those published.13
1.6. 4-Nitrophenyl 3,4,6-tri-O-acetyl-2-azido-2-deoxy-a-
D-mannopyranoside (3)
Tetraacetate 6 (0.59g, 1.58mmol) was melted with 4-
nitrophenol (0.66g, 5.37mmol) at 120ꢁC under reduced

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A. Popelova et al. / Carbohydrate Research 340 (2005) 161–166
165
1.9. 4-Nitrophenyl 3,4,6-tri-O-acetyl-b-D-glucopyranoside
(13)
7.9Hz, H-4), 4.74 (dd, 1H, J2,3 2.3Hz, H-2), 4.30 (dd,
1H, J5,6b 6.6Hz, J6a,6b 12.3Hz, H-6b), 4.23 (dd, 1H,
J6a,5 3.5Hz, H-6a), 4.04 (dd, 1H, H-3), 3.96–3.89 (m,
1H, H-5), 2.15 (s, 3H, COCH3), 2.15 (s, 3H, COCH3),
1.98 (s, 3H, COCH3); 13C NMR: d 172.65 (2C, CH3CO),
170.38 (CH3CO), 160.96 (quaternary C-arom), 143.11
(quaternary C-arom), 128.59 (2C, C-arom), 116.58
(2C, C-arom), 96.04 (C-1), 72.84 (C-5), 70.87 (C-3),
69.45 (C-4), 62.71 (C-6), 51.90 (C-2), 23.28, 20.90,
20.61 (3 · CH3CO). Anal. Calcd for C18H22N2O10: C,
50,71; H, 5.20; N, 6,57. Found: C, 50.78; H, 5.05; N,
6.87.
Tetra-O-acetate 4 (4.00g, 11.85mmol) was converted21
into bromide 12 that was immediately glycosylated with
4-nitrophenol in the presence of potassium carbonate.20
Column chromatography (1:1 toluene–ethyl acetate)
yielded glucopyranoside 13 (3.84g, 8.97mmol, 78%).
1H NMR data are in agreement with those published;22
13C NMR: d 178.88, 170.50, 169.60 (3 · CH3CO),
161.40 (quaternary C-arom), 143.16 (quaternary C-
arom), 125.72 (2C, C-arom), 116.67 (2C, C-arom),
100.13 (C-1), 74.50 (C-3), 72.32, 71.93 (C-2 and C-5),
68.08 (C-4), 62.01 (C-6), 20.71, 20.63, 20.54
(3 · CH3CO).
Acknowledgements
1.10. 4-Nitrophenyl 3,4,6-tri-O-acetyl-2-O-trifluoro-
methanesulfonyl-b-D-glucopyranoside (14)
This work was supported by the Grant Agency of the
Czech Republic (Grant No. 203/01/1018) and by the
Ministry of Education, Youth and Sports of the Czech
Republic (project No. 1561/2003).
Triflic anhydride (0.5mL, 3.07mmol) was slowly added
at 5ꢁC to a stirred solution of 13, (0.881g, 2.056mmol)
in dichloromethane–pyridine (2:1, 37mL). The mixture
was kept at 3ꢁC for 30min, and then allowed to attain
rt. After another 30min, the reaction was complete
(TLC petroleum ether, ethyl acetate 1:1, Rf 0.82) and
it was quenched by addition of water (1.5mL). The or-
ganic phase was separated and concentrated, and tolu-
ene was evaporated twice from the residue that was
dried in vacuum. The product was purified by column
chromatography (3:1 petroleum ether–ethyl acetate) to
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20
1
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