Glycosylation in room temperature ionic liquid using unprotected and unactivated donors

Article abstract of DOI:10.1016/j.carres.2006.11.022

Glycosylation in room temperature ionic liquid is demonstrated using unprotected and unactivated donors. Modest yields of simple benzyl glycosides and disaccharides of glucose, mannose and N-acetylgalactosamine were obtained in 1-ethyl-3-methylimidazolium benzoate with Amberlite IR-120 (H⁺) resin or p-toluenesulfonic acid as promoters.

Full text of DOI:10.1016/j.carres.2006.11.022

Carbohydrate Research 342 (2007) 614–620
Note
Glycosylation in room temperature ionic liquid
using unprotected and unactivated donors
Tae-Joon Park,a Michel Weıwer,b Xuejun Yuan,b Sultan N. Baytas,b Eva M. Munoz,b
¨
Saravanababu Murugesana and Robert J. Linhardta,b,c,d,
*
aDepartment of Chemical and Biological Engineering, Biotechnology 4005, Rensselaer Polytechnic Institute,
110, 8th Street, Troy, NY 12180, USA
bDepartment of Chemistry and Chemical Biology, Biotechnology 4005, Rensselaer Polytechnic Institute,
110, 8th Street, Troy, NY 12180, USA
cDepartment of Biology, Biotechnology 4005, Rensselaer Polytechnic Institute, 110, 8th Street, Troy, NY 12180, USA
dPharmaceutical Research Institute, Albany College of Pharmacy, Albany, NY 12208, USA
Received 6 June 2006; received in revised form 29 August 2006; accepted 24 November 2006
Available online 29 November 2006
Dedicated to the memory of Professor Nikolay K. Kochetkov
Abstract—Glycosylation in room temperature ionic liquid is demonstrated using unprotected and unactivated donors. Modest
yields of simple benzyl glycosides and disaccharides of glucose, mannose and N-acetylgalactosamine were obtained in 1-ethyl-3-
methylimidazolium benzoate with Amberlite IR-120 (H+) resin or p-toluenesulfonic acid as promoters.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Glycosylation; Room temperature ionic liquids; Unprotected donor; Unactivated donor
Glycosylation occurs between a donor and an acceptor
in the presence of a promoter, which activates the
donor. Glycosylation reactions in the synthesis of com-
plex carbohydrates can prove to involve challenging
chemistry. There are various factors that need to be con-
sidered when carrying out the synthesis of glycosides,
including the presence and choice of a leaving group
at the anomeric position of the donor, the manipulation
of protecting groups in both donor and acceptor, the
architecture of donor and acceptor, the solvent system
and the choice of promoter.1–3 Since the initial introduc-
tion of Fischer glycosylation,4 many innovative glyco-
sylation strategies have been developed that have
improved overall yield, chemoselectivity, regioselecti-
vity, and stereoselectivity.5 Most of these glycosylation
reactions require temporary protection of both acceptor
and donor. There is a plethora of literature describing
the introduction of protecting groups on both donor
and acceptor, the activation of donor, glycosylation
reactions, recovery of oligosaccharide products, and
the deprotection of oligosaccharide products. These
strategies involve extensive manipulation of protecting
groups and often a large number of synthetic steps.
Glycosylation using unprotected and unactivated
donors is often preferable as it can reduce the number
of steps, enhance reactivity, allow for a different stereo-
chemistry, and increase prospects for further process
modifications.6,7 The chemical synthesis of unprotected
carbohydrates possesses a number of challenges, includ-
ing their poor solubility in most conventional organic
solvents. Only very polar organic solvents, such as form-
amide, dimethylformamide, dimethyl sulfoxide, and pyr-
idine, easily dissolve significant amounts of sugars.8
Furthermore, these are reactive, nonvolatile solvents,
difficult to dry and thus, they pose problems for both
carrying out glycosylation reactions and the recovery
*
Corresponding author. Tel.: +1 518 276 3404; fax: +1 518 276
3405; e-mail: linhar@rpi.edu
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.11.022

T.-J. Park et al. / Carbohydrate Research 342 (2007) 614–620
615
of products. It is important to investigate new solvent
systems that dissolve carbohydrates, support glycosyl-
ation reactions of unprotected sugars, and facilitate
product recovery.
of galactose oligomers was also possible using these
novel solvents.
D-Glucose (Glc), D-mannose (Man), D-galactose
(Gal), and N-acetyl-D-galactosamine (GalNAc) were
used as unactivated donors in the RTIL, 1-ethyl-3-
methylimidazolium benzoate ([emIm][ba]), with Amber-
lite IR-120 (H+) resin or p-toluenesulfonic acid (TsOH)
as promoters to form an array of O-glycosylated prod-
ucts. The RTIL [emIm][ba] was shown in our previous
studies to be a useful solvent and catalyst for the protec-
tion of carbohydrates.13
Our initial studies utilized benzyl alcohol as a glycosyl
acceptor. Monosaccharide donors were used as a,b-ano-
meric mixtures, as determined from their 1H NMR spec-
tra in D2O. Benzyl glycosidation of Glc, Man, and
GalNAc afforded fair to good isolated yields of exclu-
sively a-glycosides (Table 1). RTILs are relatively vis-
cous liquids, [emIm][ba] with a viscosity of 425 cP at
25 ꢁC, making both stirring and product recovery
difficult.13
Isolated yields of glycosylation products could be
improved by increasing the reaction temperature and/
or the reaction time. Further increase in reaction time
or reaction temperature failed to improve the isolated
product yields. Like other sugars (Glc and Man), Gal-
NAc afforded only the a-glycoside, which is in keeping
with the a-selectivity reported previously for the reaction
of GalNAc with benzyl alcohol in the presence of HCl at
70–80 ꢁC.15 While the previous success of synthesis of
benzyl a-glycoside of GalNAc by Fischer glycosidation
Room temperature ionic liquids (RTILs) are becom-
ing increasingly used as solvents for a wide variety of
chemical reactions,9 including the reactions used in carbo-
hydrate synthesis.10–12 RTILs also display desirable
solvent properties such as low vapor pressure, low vola-
tility, thermal stability, large liquidus range, and tunable
physical properties, and are capable of dissolving both
polar and nonpolar solutes. These ionic solvents have
the potential of replacing conventional volatile organic
solvents in carbohydrate chemistry. Our previous stud-
ies showed that dialkylimidazolium benzoate RTILs
are useful solvent/catalysts for the peracetylation and
perbenzoylation of simple and sulfated saccharides with
good to excellent yields using short reaction times.13
A
number of reactions involving carbohydrates have
utilized RTILs, resulting in new methodologies and
enhanced yields.10,14
In this work, we report the glycosidation of various
simple, unprotected monosaccharides in RTILs to give
benzyl glycosides, disaccharides, and oligosaccharides.
RTILs facilitate the use of unactivated and unprotected
donors in these reactions, resulting in a simple synthetic
strategy involving a single glycosylation step. Stereo-
selectivity is observed in these glycosylation reactions
including a-selective glycosylation using N-acetyl-D-
galactosamine (GalNAc) donor. Finally, the synthesis
Table 1. Benzyl a-glycosidation of unprotected and unactivated monosaccharides in [emIm][ba]a
OH
[emIm][ba]
O
O
HO
HO
OH
+
Amberlite IR-120 (H+)
O
Entry
1
Glycosyl donor
Glc
Product
Acceptor (equiv)
20
Time (h)
Temp (ꢁC)
Yieldb (%)
OH
16
6
30
50
20
64
O
HO
HO
HO
OBn
1
OH
HO
O
HO
HO
2
Man
20
10
16
6
30
50
33
61
OBn
2
OH
HO
OH
O
3
GalNAc
6
50
27
AcHN
OBn
3
a Carried out under argon.
b Isolated yields.

616
T.-J. Park et al. / Carbohydrate Research 342 (2007) 614–620
suggests that ionic liquid is unnecessary, the reaction of
GalNAc with benzyl alcohol at 30–50 ꢁC in the presence
of Amberlite (H+) fails to take place in the absence of
ionic liquid. The added ionic liquid made these reactions
possible under relatively mild conditions preventing the
formation of undesired side products. More detailed
mechanistic studies are underway to understand the
precise role of ionic liquid in these reactions.
in the benzyl glycosidation afforded modest yields of the
a-linked disaccharides. The a-configuration was inferred
from the chemical shifts and coupling constants of the
anomeric proton signals. The reduced yields obtained
using sugar-based acceptors, in place of benzyl alcohol
acceptor, is believed to be associated with the increased
viscosity of the reaction mixture, decreasing the mobility
of the reaction components.
Our efforts next turned toward the synthesis of di-
saccharides from unprotected donors and partially
protected acceptors using the same strategy. Glycosyl
acceptors were synthesized using standard methods
from methyl a-D-glucoside. 2,3,4-Tri-O-allyl- or 2,3,4-
tri-O-benzyl-protected methyl a-D-glucoside leaves the
primary 6-hydroxyl group unprotected and available
for reaction. Attempts to perform glycosylation reac-
tions of these acceptors with unprotected Glc, Man,
and GalNAc donors under conditions successfully used
The mobility of the reactants could be slightly
enhanced by replacing the insoluble promoter (Amberite
IR-120 (H+) resin) by the soluble promoter, TsOH,
and increasing the reaction temperature. The incorpora-
tion of smaller allyl protecting groups into the acceptor
also improved the reaction yields. This glycosylation
strategy forms disaccharides in fair yields, with excellent
stereoselectivity (Table 2). While TLC showed each
reaction to be nearly complete with a single major prod-
uct formed, the isolated yields were modest. We ascribe
Table 2. Synthesis of disaccharides using unactivated and unprotected donors in [emIm][ba]a
OH
O
HO
[emIm][ba]
TsOH
O
O
HO
RO
OH
+
O
OMe
O
RO
4 R=All
5 R=Bn
OMe
Entry
Donor
Glc
Acceptor
Product
Donor/acceptor ratio
Time (h)
Temp (ꢁC)
Yieldb (%)
OH
O
HO
HO
1/10
1/1
1/10
6
4
4
50
50
80
35
25
36
HO
1
4
O
O
AllO
AllO
AllO
AllO
OMe
6
7
OH
OH
O
HO
HO
2
Man
4
1/10
1/2
6
6
50
50
41
22
O
O
AllO
AllO
OMe
OH
OH
O
HO
HO
3
Man
5
1/2
10
50
20
O
O
BnO
BnO
BnO
OMe
8
OH
OH
O
HO
AcHN
4
GalNAc
4
1/10
6
50
20
O
O
AllO
AllO
AllO
OMe
9
a Carried out under argon.
b Isolated yields.

T.-J. Park et al. / Carbohydrate Research 342 (2007) 614–620
617
OH
OH
O
O
OH
O
+
HO
OH
O
HO
O
O
10
[emIm][ba], Amberlite IR-120 (H+)
glycosylation and partial deprotection
OH
OH
OH
OH
OH
O
OH
O
OH
O
OH
O
A
A
A
A
HO
HO
HO
HO
+
+
+
HO
OH
HO
HO
OH
HO
O
O
O
O
O
O
O
O
O
O
HO
OH
O
OH
HO
O
D
B
C
HO
A
HO
O
O
O
O
12
12'
12''
12'''
[emIm][ba], Amberlite IR-120 (H+),
continuous glycosylation and deprotection
10
trisaccharides
+
tetrasaccharides
+
pentasaccharides
Amberlite H+, H2O
+
hexasaccharides....
OH
OH
O
HO
HO
OH
O
O
HO
n
HO
O
OH
O
HO
OH
HO
mixture of oligosaccharides
Scheme 1. Synthesis of galactose oligosaccharides in [emIm][ba].
this modest yield to the difficulty in recovering the
products from benzoate-based ionic liquids.13
Deprotection of disaccharide products by treatment
with Amberlite IR-120 (H+) resin in water at 80 ꢁC for
4 h affords the exclusively a-linked disaccharide 12
(41%) (Table 3). Treatment of the entire reaction mix-
ture with Amberlite IR-120 (H+) resin afforded a mix-
ture of unprotected a-(1!6)-linked Gal oligosaccharides
11 (Fig. 1c).
In summary, benzyl glycosides were synthesized from
unactivated donors in good yield in a single synthetic
step. Glycosylation of partially protected monosaccha-
ride acceptors gave the expected disaccharides with
a-stereoselectivity and without protection or covalent
activation of the glycosyl donor. Additional studies
including acceptors having multiple unprotected hydr-
oxyl groups and a wider array of unactivated donors
are currently under way.
Finally, the synthesis of disaccharides has been
extended to oligosaccharide synthesis by utilizing an
isopropylidene-protected acceptor (Scheme 1). While
strategies using both unprotected donor and unpro-
tected acceptor were unsuccessful, we found that the
glycosyl acceptor 1,2:3,4-di-O-isopropylidene-a-D-galac-
topyranose (10) could be used for the synthesis of
a-(1!6)-linked galactose oligosaccharides. This reaction
makes use of the instability of the isopropylidene pro-
tecting group under acidic conditions to afford di-, tri-,
tetra-, and penta-saccharide products within 4 h at
50 ꢁC, as demonstrated by MS analysis (Fig. 1a). Frac-
tionation of the reaction mixture afforded the four disac-
charides shown in Scheme 1 (see Fig. 1b for MS).

618
T.-J. Park et al. / Carbohydrate Research 342 (2007) 614–620
meter and Agilent 1100 series LC/MSD trap, respec-
tively. Thin-layer chromatography (TLC) was carried
out using E. Merck plates of Silica Gel 60 with fluorescent
indicator and the spots were visualized by dipping the
plates into 5% sulfuric acid in ethanol followed by
heating. Flash chromatography was performed using
silica gel (230–400 mesh, Natland International
Corporation).
1.2. Benzyl a-D-glucopyranoside (1)
Amberlite IR-120 (H+) (300 mg) was added to a soln
of D-glucose (47 mg, 0.26 mmol) and anhyd benzyl
alcohol (562.3 mg, 5.2 mmol) in [emIm][ba] (312 mg,
1.34 mmol) at room temperature or 50 ꢁC and the
reaction mixture was stirred in an argon atmosphere
until the reaction was complete as demonstrated by
TLC. After adding MeOH (5 ml), the resin was
removed by filtration and the mixture was concentrated
by rotary evaporation. Flash chromatography of the
residue [CH2Cl2!CH2Cl2–MeOH (24:1)] gave pure 1
1
(45 mg, 64% at 50 ꢁC). H NMR (500 MHz, D2O): d
7.47–7.39 (5H, ArH), 5.01 (1H, d, J 4 Hz, H-1), 4.77
(1H, d, J 11.5 Hz, CH2Bn), 4.61 (1H, d, J 11.5 Hz,
CH2Bn), 3.91 (1H, dd, J1 2 Hz, J2 12.5 Hz, H-6a),
3.78–3.65 (3H, m, H-6b, H-5, H-3), 3.55 (1H, dd, J1
4 Hz, J2 10 Hz, H-2), 3.47–3.37 (1H, m, H-4); 13C
NMR (300 MHz, D2O): d 137.29, 128.96, 128.76,
128.54, 97.90, 76.19, 73.35, 72.18, 71.55, 69.91, 60.64;
HRMS: calcd for C13H18O6Na [M+Na]+ 293.1025,
found m/z 293.1028.
1.3. Benzyl a-D-mannopyranoside (2)
Glycoside 2 was obtained by the same protocol as
described for 1. Flash chromatography afforded
Figure 1. Negative-ion mode ESI/MS spectra of oligomerization
reaction: (a) the oligosaccharide mixture of unprotected and partially
protected galactopyranosyl residues comprise compounds 12000 (AD,
see Scheme 1 for definition of A, B, and D), 13 (AAD), 14 (ABD), 15
(AAAD), 16 (ABBD), and 17 (AAAAD) that are observed as their
chloride adducts, (b) fractionation of the reaction mixture and (c)
oligosaccharide mixture after deprotection: dimer (12), trimer (AAA),
and tetramer (AAAA) are observed as their chloride adducts.
compound
2
(43 mg, 61% at 50 ꢁC). 1H NMR
(500 MHz, D2O): d 7.44–7.39 (5H, ArH), 4.96 (1H, J
2 Hz, H-1), 4.76 (1H, d, J 11 Hz, CH2Bn), 4.57 (1H, d,
J 11 Hz, CH2Bn), 3.94 (1H, dd, J1 2 Hz, J2 3.5 Hz, H-
2), 3.86 (1H, dd, J1 1.5 Hz, J2 12 Hz, H-5), 3.80–3.74
(2H, m, H-6a, H-3), 3.70–3.64 (2H, m, H-4, H-6b);
13C NMR (300 MHz, D2O): d 136.84, 128.96, 128.76,
128.62, 99.49, 73.08, 70.73, 70.20, 69.60, 66.88, 61.01;
HRMS: calcd for C13H18O6Na [M+Na]+ 293.1017,
found m/z 293.1028.
1. Experimental
1.1. General methods
1.4. Benzyl 2-acetamido-2-deoxy-a-D-galactopyranoside
(3)
Room temperature ionic liquid [emIm][ba] was synthe-
sized according to the reported procedure13 and all
chemicals were purchased from Fisher, Sigma, or
Aldrich. 1H NMR and 13C NMR spectra were acquired
at 25 ꢁC, in CDCl3 or D2O (Varian). Chemical shifts (d)
were indicated in parts per million and coupling
constants (J) in Hertz. HRMS and LRMS were recorded
on Micromass Autospec high resolution mass spectro-
Amberlite IR-120 (H+) (300 mg) was added to a soln of
D-GalNAc (57.5 mg, 0.26 mmol) and anhyd benzyl
alcohol (281.2 mg, 2.6 mmol) in [emIm][ba] (312 mg,
1.34 mmol) at room temperature or 50 ꢁC and the mix-
ture was stirred under argon as described for 1. The mix-
ture was then purified by flash chromatography on silica

T.-J. Park et al. / Carbohydrate Research 342 (2007) 614–620
Table 3. One-pot synthesis of oligosaccharides mixturea
619
Donor
Acceptor
Product
n
Time (h)
Temp (ꢁC)
Yieldb (%)
OH
OH
O
HO
HO
O
OH
P0
4
50
50c
O
HO
n
HO
O
OH
O
HO
Gal
10
HO
OH
11
OH
OH
O
HO
HO
O
OH
4
50
41
O
HO
HO
OH
12
a Carried out under argon.
b Isolated yields.
c Yield is estimated from average product size.
gel to afford 3 (22 mg, 27%). 1H NMR (500 MHz, D2O):
d 7.47–7.40 (5H, ArH), 6.19 (1H, broad signal, NHAc),
4.97 (1H, d, J 4 Hz, H-1), 4.71 (1H, d, J 12 Hz, CH2Bn),
4.51 (1H, d, J 12 Hz, CH2Bn), 4.11 (1H, dd, J1 4 Hz, J2
11 Hz, H-2), 4.03 (1H, m, H-5), 3.99 (1H, d, J 3 Hz, H-
4), 3.92 (1H, dd, J1 3 Hz, J2 11 Hz, H-3), 3.75 (1H, m,
H-6a), 3.73 (1H, m, H-6b), 1.96 (3H, s, CH3Ac); 13C
NMR (300 MHz, D2O): d 172.22, 136.54, 129.18,
128.43, 128.41, 99.18, 72.77, 69.90, 69.29, 66.58, 60.70,
50.11, 22.02; HRMS: calcd for C15H21NO6Na
[M+Na]+ 334.1266, found m/z 334.1267.
1.6. Methyl 2,3,4-tri-O-allyl-6-O-(a-D-mannopyranosyl)-
a-D-glucopyranoside (7)
Disaccharide 7 was obtained by the same protocol as de-
1
scribed for 6. H NMR (500 MHz, CDCl3): d 6.01–5.84
(3H, m, 3 · CHAll), 5.34–5.14 (6H, m, 3 · CH2 All), 4.92
(1H, br s, H-10), 4.74 (1H, d, J 3.5 Hz, H-1), 4.41–4.05
(6H, m, 3 · CH2 All), 3.99–3.92 (3H, m, H-6b0, H-40,
H-20), 3.89–3.82 (2H, m, H-6a, H-30), 3.78–3.63 (4H,
m, H-5, H-3, H-6a0, H-6b,), 3.60 (1H, m, J 10 Hz, H-
50), 3.42–3.36 (1H, m, H-2), 3.39 (3H, s, OCH3), 3.30
(1H, t, H-4); 13C NMR (300 MHz, CDCl3): d 135.37,
134.98, 117.88, 116.92, 100. 35, 98.24, 81.75, 79.78,
75.72, 74.50, 74.13, 73.88, 72.76, 72.12, 71.97, 70.52,
69.88, 66.45, 64.78, 55.34; HRMS: calcd for
C22H36O11Na [M+Na]+ 499.2156, found m/z 499.2155.
1.5. Methyl 2,3,4-tri-O-allyl-6-O-(a-D-glucopyranosyl)-a-
D-glucopyranoside (6)
A mixture of D-glucose (17.48 mg, 0.097 mmol), accep-
tor
4
(305 mg, 0.97 mmol), and TsOH (9 mg,
0.047 mmol) in [emIm][ba] (300 mg, 1.29 mmol) was
stirred under argon for 6 h at 50 ꢁC. Purification by flash
chromatography on silica [CH2Cl2!CH2Cl2–MeOH
(28:1)!(19:1)] then gave disaccharide 6 (16 mg, 35%).
1H NMR (500 MHz, CDCl3): d 6.02–5.85 (3H, m,
3 · CHAll), 5.32–5.15 (6H, m, 3 · CH@CH2 All), 4.93
(1H, d, J 3 Hz, H-10), 4.76 (1H, d, J 3 Hz, H-1), 4.40–
4.08 (8H, m, H-50, H-40, 3 · CH2–CHAll), 3.90–3.71
(5H, m, H-6a, H-6b, H-4, H-3, H-30), 3.63 (1H, m,
H-6b0), 3.45–3.32 (4H, m, H-5, H-2, H-6a0, H-20), 3.41
(3H, s, OCH3); 13C NMR (300 MHz, CDCl3): d
134.74, 134.51, 118.20, 117.34, 99.09, 97.68,
79.15, 75.00, 73.58, 72.90, 72.72, 71.92, 70.81, 70.63,
67.97, 65.85, 62.48, 61.95, 60.34, 55.38; HRMS: calcd
for C22H36O11Na [M+Na]+ 499.2164, found m/z
499.2155.
1.7. Methyl 2,3,4-tri-O-benzyl-6-O-(a-D-mannopyranos-
yl)-a-D-glucopyranoside (8)
A mixture of D-mannose (7.5 mg, 0.042 mmol), acceptor
5
(38.8 mg, 0.0836 mmol), and TsOH (9 mg,
0.047 mmol) in [emIm][ba] (100 mg, 0.43 mmol) was
stirred under argon for 10 h at 50 ꢁC. Purification by
flash chromatography on silica [CH2Cl2!CH2Cl2–
MeOH (28:1)!(19:1)] then gave disaccharide
8
1
(5.4 mg, 20%). H NMR (500 MHz, CDCl3): d 7.34–
7.21 (15H, 3 · ArH), 4.97 (1H, d, J 11 Hz, CH2Bn),
4.90 (1H, d, J 11 Hz, CH2Bn), 4.82 (1H, br s, H-10),
4.78 (1H, d, J 11 Hz, CH2Bn), 4.74 (1H, d, J 12 Hz,
CH2Bn), 4.63 (1H, d, J 12 Hz, CH2Bn), 4.56 (1H, d, J
3.5 Hz, H-1), 4.52 (1H, d, J 11 Hz, CH2Bn), 3.99–
3.90 (3H, m, H-3, H-50, H-20), 3.82–3.69 (4H, m,

620
T.-J. Park et al. / Carbohydrate Research 342 (2007) 614–620
H-6a, H-5, H-6a0, H-6b0), 3.57–3.50 (3H, m, H-6b, H-2,
H-30), 3.46–3.42 (2H, m, H-4, H-40), 3.32 (3H, s, OCH3);
13C NMR (300 MHz, CDCl3): d 138.43, 138.39, 138.24,
128.68, 128.63, 128.26, 127.91, 127.72, 100.38, 98.11,
82.25, 80.65, 77.45, 77.39, 77.02, 76.96, 75.04, 74.34,
73.55, 73.25, 70.94, 68.57, 60.61, 55.38; HRMS: calcd
for C34H42O11Na [M+Na]+ 649.2629, found m/z
649.2625.
H-10), 4.22 (1H, dd, J1 3.5 Hz, J2 8 Hz, H-50), 4.09–4.04
(2H, m, H-6a, H-20), 3.97–3.90 (3H, m, H-6b, H-5, H-
30), 3.88–3.76 (3H, m, H-4, H-2, H-40), 3.74–3.67 (2H,
m, H-3, H-6b0) 3.65–3.61 (1H, m, H-6a0); b-anomer,
5.02 (1H, d, J 1.5 Hz, H-10), 4.56 (1H, d, J 7.75 Hz,
H-1), 4.22 (1H, dd, J1 3.5, J2 8 Hz, H-50), 4.09–4.04
(2H, m, H-6a, H-20), 3.97–3.90 (2H, m, H-5, H-30),
3.88–3.76 (3H, m, H-6b, H-4, H-40), 3.74–3.67 (1H, m,
H-6b0), 3.65–3.61 (2H, m, H-6a0, H-3), 3.47 (1H, dd,
J1 7.75 Hz, J2 10 Hz, H-2); 13C NMR (300 MHz,
D2O): d 107.95, 96.63, 92.51, 83.05, 81.19, 76.88,
73.88, 72.89, 71.99, 70.99, 69.08, 67.6, 62.87; LRMS:
calcd for C12H22O11Na [M+Na]+ 365.0, found m/z
365.0.
1.8. Methyl 2,3,4-tri-O-allyl-6-O-(2-acetamido-2-deoxy-
a-D-galactopyranosyl)-a-D-glucopyranoside (9)
Disaccharide 9 was obtained by the same protocol as de-
1
scribed for 6. H NMR (500 MHz, CDCl3): d 5.99–5.90
(3H, m, 3CHAll), 5.34–5.19 (6H, m, 3 · CH2 All), 4.84
(1H, d, J 3.5 Hz, H-10), 4.77 (1H, d, J 3.5, H-1), 4.36–
4.12 (6H, m, 3 · CH2 All), 3.92–3.76 (6H, m, H-6a, H-
6b, H-3, H-6b0, H-50, H-30), 3.67–3.56 (3H, m, H-5, H-
6a0, H-40), 3.51 (1H, m, H-2), 3.43 (3H, s, OCH3),
3.37–3.30 (2H, m, H-4, H-20), 1.68 (3H, s, CH3CO);
13C NMR (300 MHz, CDCl3): d 171.27, 135.13,
134.70, 133.31, 117.64, 117.07, 116.56, 106.62, 98.14,
86.69, 81.29, 79.45, 77.52, 77.25, 74.21, 73.79, 72.58,
70.55, 69.59, 65.41, 64.36, 61.42, 55.20, 52.12, 23.05;
LRMS: calcd for C24H39NO11Na [M+Na]+ 540.2,
found m/z 540.2.
References
1. Green, L. G.; Ley, S. V. Carbohydr. Chem. Biol. 2000, 1,
427–448.
2. Nitz, M.; Bundle, D. R. Glycoscience 2001, 2, 1497–
1542.
3. Ernst, B.; Hart, G. W.; Sinay, P. Carbohydrates in
¨
Chemistry and Biology; Wiley: Weinheim, Germany, 2000.
4. Fischer, E. Ber. Dtsch. Chem. Ges. 1893, 26, 2400–
2412.
5. Balzer, D.; Luders, H. Nonionic Surfactants—Alkyl Poly-
glucosides; Marcel Dekker: New York, 2000.
6. Hanessian, S. Preparative Carbohydrate Chemistry; Mar-
cel Dekker: New York, 1997.
1.9. 6-O-(a-D-Galactopyranosyl)-D-galactopyranose (12)
7. Hanessian, S.; Lou, B. L. Chem. Rev. 2000, 100, 4443–
4463.
A mixture of D-galactose (152.82 mg, 0.848 mmol),
acceptor 10 (1260 mg, 4.84 mmol), and Amberlite IR-
120 (H+) (300 mg) in [emIm][ba] (1200 mg, 5.155 mmol)
was stirred under argon at 50 ꢁC. After 4 h, water was
added and the mixture was filtered to remove Amberlite
IR-120 (H+) and benzoic acid liberated from [emIm]-
[ba]. The filtrate was treated with Amberlite IR-120
(H+) (1500 mg) in water at 80 ꢁC for 4 h to remove the
protecting groups to provide unprotected oligosaccha-
ride 12. Purification by flash chromatography [ethyl ace-
tate–MeOH–water (17:2:1)!(7:2:1)!(11:6:3)] then gave
oligosaccharide 12. 1H NMR (500 MHz, D2O): d a-ano-
mer, 5.24 (1H, d, J 3.5 Hz, H-1), 5.02 (1H, d, J 1.5 Hz,
8. Foley, K. M.; Griffin, C. C.; Amaya, E. U.S. Patent App.
898,124, 1990.
9. Sheldon, R. Chem. Commun. 2001, 23, 2399–2407.
10. Murugesan, S.; Linhardt, R. J. Curr. Org. Synth. 2005, 2,
437–451.
11. Rencurosi, A.; Lay, L.; Russo, G.; Caneva, E.; Poletti, L.
Carbohydr. Res. 2006, 341, 903–908.
12. Rencurosi, A.; Lay, L.; Russo, G.; Caneva, E.; Poletti, L.
J. Org. Chem. 2005, 70, 7765–7768.
13. Murugesan, S.; Karst, N.; Islam, T.; Wiencek, J. M.;
Linhardt, R. J. Synlett 2003, 9, 1283–1286.
14. Poletti, L.; Rencurosi, A.; Lay, L.; Russo, G. Synlett.
2003, 15, 2297–2300.
15. Sharma, M.; Potti, G. G.; Simmons, O. D.; Korytnyk, W.
Carbohydr. Res. 1987, 162, 41–51.