A carbohydrate-anion recognition system in aprotic solvents

Article abstract of DOI:10.1002/asia.201301617

A carbohydrate-anion recognition system in nonpolar solvents is reported, in which complexes form at the B-faces of β-D-pyranosides with H1-, H3-, and H5-cis patterns similar to carbohydrate-π interactions. The complexation effect was evaluated for a range of carbohydrate structures; it resulted in either 1:1 carbohydrate-anion complexes, or 1:2 complex formation depending on the protection pattern of the carbohydrate. The interaction was also evaluated with different anions and solvents. In both cases it resulted in significant binding differences. The results indicate that complexation originates from van der Waals interactions or weak CHA^- hydrogen bonds between the binding partners and is related to electron-withdrawing groups of the carbohydrates as well as increased hydrogen-bond-accepting capability of the anions. Facial recognition: A carbohydrate-anion recognition system is reported, in which complexes form at the B-faces of β-D-pyranosides with H1-, H3-, and H5-cis patterns similar to carbohydrate-π interactions (see scheme). The interaction was also evaluated with different anions and solvents. In both cases it resulted in significant binding differences.

Full text of DOI:10.1002/asia.201301617

FULL PAPER
DOI: 10.1002/asia.201301617
A Carbohydrate–Anion Recognition System in Aprotic Solvents
[
a]
[a]
[b]
Bo Ren, Hai Dong,* and Olof Ramstrçm*
Abstract: A carbohydrate–anion recog-
nition system in nonpolar solvents is
reported, in which complexes form at
the B-faces of b-d-pyranosides with
H1-, H3-, and H5-cis patterns similar
to carbohydrate–p interactions. The
complexation effect was evaluated for
a range of carbohydrate structures; it
resulted in either 1:1 carbohydrate–
anion complexes, or 1:2 complex for-
mation depending on the protection
pattern of the carbohydrate. The inter-
action was also evaluated with different
anions and solvents. In both cases it re-
sulted in significant binding differences.
The results indicate that complexation
originates from van der Waals interac-
tions or weak CH···A hydrogen bonds
between the binding partners and is re-
lated to electron-withdrawing groups of
the carbohydrates as well as increased
hydrogen-bond-accepting capability of
the anions.
À
Keywords: anions · carbohydrates ·
molecular recognition · pi interac-
tions · supramolecular chemistry
Introduction
Carbohydrate–aromatic interactions represent a widely in-
[1]
vestigated research area in biochemistry, in part owing to
the fact that carbohydrate–protein recognition plays an im-
[2]
portant role in many biological processes. This type of in-
teraction is a common feature in the recognition of carbohy-
drates, and it is dependent on the electronic nature of the ar-
[
6]
[3]
Scheme 1. Carbohydrate–anion recognition.
omatic group. The interactions generally occur between
[4]
the B-face of the carbohydrate, particularly the “three-
point landing surface” that consists of the H1, H3, and H5
protons of the pyranosides, and the face of an aromatic side
anions and the axial H1, H3, and H5 protons of the carbo-
hydrates. The interaction proved in this case to be fairly
strong, and H NMR spectroscopic titration clearly indicated
[1c,j,5]
1
chain.
However, these interactions are so weak that it is
difficult to provide direct evidence showing that they con-
tribute to the driving force of biological processes.
that the driving force stems from the contribution of the
CH–anion interactions.
Recently, we discovered a novel carbohydrate–anion rec-
ognition mechanism very similar to these systems
Anion recognition has been reported extensively and is
well known to often be strongly affected by solvent effects,
as a consequence of the related high free energies of solva-
[6]
(
Scheme 1). With a similar three-point binding motif as for
[7]
the carbohydrate–p interactions, this binding occurs between
tion and associated coordinative saturation. Hence, a po-
tential anion receptor must effectively compete with the sol-
vent environment for any anion recognition to take place,
which explains the particular appearance of these carbohy-
drate–anion recognition systems in nonpolar solvents. In the
present study, we set out to address these effects, and fur-
ther examine the novel host–guest interaction discovered
with respect to the host structure, anion type, and solvent ef-
fects.
[
a] B. Ren, Prof. H. Dong
School of Chemistry and Chemical Engineering
Huazhong University of Science and Technology
Luoyu Road 1037, 430074, Wuhan (P.R. China)
Fax : (+86)27-87793242
E-mail: hdong@mail.hust.edu.cn
[
b] Prof. O. Ramstrçm
Department of Chemistry
The carbohydrate–anion recognition initially came to our
attention during investigation of supramolecular control in
KTH-Royal Institute of Technology
Teknikringen 30, 10044, Stockholm (Sweden)
E-mail: ramstrom@kth.se
[6]
carbohydrate epimerization. Prompted by the formation of
a carbohydrate–nitrite complex, the Lattrell–Dax (nitrite-
mediated) epimerization reaction shown in Scheme 2 was
either activated or deactivated, depending on whether the
nucleophilic reagent attacked from the same or from the op-
posite direction as the anion binding. For example, when the
methyl b-d-galactopyranoside derivatives 1 were tested in
ꢀ
2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co.
KGaA.
This is an open access article under the terms of the Creative Com-
mons Attribution-NonCommercial-NoDerivs License, which permits
use and distribution in any medium, provided the original work is
properly cited, the use is non-commercial and no modifications or
adaptations are made.
Chem. Asian J. 2014, 9, 1298 – 1304
1298 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Olof Ramstrçm, Hai Dong, and Bo Ren
With acetyl groups (compound 3), very few changes were
recorded for the chemical shift values of H1, H3, and H5,
probably indicating very weak supramolecular effects be-
tween the carbohydrate and the nitrite anions. However,
when one of the acetylated hydroxyl groups was changed to
a more electron-withdrawing fluoride or triflate group (com-
pounds 1a, 2a, and 4), relatively larger changes in the chem-
ical shift values of H1, H3, and H5 were recorded likely
owing to the stronger supramolecular effect. With benzoyl
groups (compound 5), an intermediate supramolecular
effect was observed, and when one of the benzoyl groups
was changed to a more electron-withdrawing triflate group
(
compounds 1b and 2b), larger changes in the chemical-
Scheme 2. Supramolecular control from carbohydrate–anion recognition.
shift values of H1, H3, and H5 were again observed. Analo-
gously, when one of the benzoyl groups was instead changed
to a less electron-withdrawing thioacetyl group (compound
6), a much weaker effect was observed. These results indi-
cate that the supramolecular effect is related to electron-
withdrawing groups of these carbohydrates.
this reaction, the rates increased in the order of CHCl <
3
CH Cl <CH CN<DMF, benzene and toluene. However,
2
2
3
although the Lattrell–Dax reaction proceeded very well in
CH CN and DMF for methyl b-d-galactopyranoside deriva-
3
tives 2, it completely failed in benzene and toluene. The for-
Carbohydrates with different anions in [D]benzene were
also tested. The results of these tests indicate that the stabil-
ity of the carbohydrate/anion complex is strongly associated
with the hydrogen bonding ability of the anions. Compounds
mation of the carbohydrate–anion complex was revealed
[6]
through NMR spectroscopic analyses.
1
b and 2a were tested in [D]benzene with 10 equivalents of
Results and Discussion
benzoate, chloride, and bromide, respectively (Table 2). The
[6]
As previously demonstrated, the supramolecular carbohy-
drate–anion recognition effect is likely due to charge/dipole
attraction and/or weak hydrogen bonding between the CH
1
Table 2. Relative H shifts (Dd) of derivatives 1b and 2a in the presence
and absence of different anions in [D]benzene. Tetrabutylammonium
TBA) anion salts (10 equiv) were used throughout.
(
1-, 3-, 5-position three-point binding motif of galactosides
Compound Anion DH1 DH2
DH3 DH4 DH5 DH6
a
DH6
b
and anions. This effect should be general, and the supra-
molecular carbohydrate/anion recognition could be envis-
aged to also occur between other carbohydrates with
an H1-, H3-, and H5-cis pattern and other anions. The ef-
fects could furthermore be accentuated by electron-with-
drawing groups. To further explore these effects, a series of
fully protected glycosides carrying electron-withdrawing
groups were evaluated in [D]benzene with a large excess
amount of nitrite anions. The results of these tests indeed in-
dicate the interaction between nitrite anions and other car-
bohydrates that hold the H1-, H3-, and H5-cis pattern
À
1
1
1
2
2a
2a
b
b
b
a
BzO
Cl
Br
1.03 À0.08 0.78 0.27 1.60
0.21
0.09
0.08
0.20
0.14
0.11
0.30
0.14
0.11
0.12
0.14
0.11
À
0.63
0.61
0.50
0.45
0.40
0.04 0.75 0.17 0.84
0.03 0.67 0.16 0.81
0.05 0.63 0.37 0.47
0.10 0.68 0.37 0.42
0.08 0.63 0.33 0.37
À
À
BzO
À
Cl
À
Br
order of the hydrogen-bonding ability of these anions is
À
À
À [8]
BzO >Cl >Br , and it was found that the chemical shift
differences of H1, H3, and H5 produced by these anions fol-
lowed the same pattern. For the benzoate anions, the pro-
tons shifted downfield by d=1.03, 0.78, and 1.60 ppm for
compound 1b and by d=0.50, 0.63, and 0.47 for compound
2a. For the chloride anions, the protons in positions 1, 3,
and 5 shifted downfield by d=0.63, 0.75, and 0.84 ppm for
compound 1b and by d=0.45, 0.68, and 0.42 for compound
(
Table 1).
1
Table 1. Comparison of H chemical shifts of several b-d-glycosides
before and after addition of nitrite anions (20 equiv) in benzene.
2
a. For the bromide anions, downfield shifts by d=0.61,
0
.67, and 0.81 ppm for compound 1b and by d=0.40, 0.63,
and 0.37 for compound 2a were recorded.
Owing to poor solubility, dry tetrabutylammonium fluo-
ride (TBAF) and tetrabutylammonium iodide (TBAI) could
not be tested in this case. High concentrations of TBAF also
led to complex side reactions, such as acyl group migration
and deprotonation. Thus, compound 1b was tested in
Compound DH1 DH3
DH5 Compound DH1 DH3 DH5
1
1
3
5
a
b
0.52
0.82
0.02
0.24
0.68
1.03
0.80
1.14
0.06
0.34
2a
2b
4
0.48
0.78
0.07
0.06
0.74
0.44
0.06
0.01
0.47
0.88
0.1
À0.02
[
D]benzene with only 0.3 equivalents of TBAF. It was found
0.09
6
0.05
À
that the chemical shift difference of F shifted downfield by
Chem. Asian J. 2014, 9, 1298 – 1304
1299 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Olof Ramstrçm, Hai Dong, and Bo Ren
compound 7 and tetrabutylammonium nitrite in [D]benzene
Figure 2). Analysis of the results of these experiments indi-
(
cated a 1:2 carbohydrate/nitrite ratio of the binding partners,
in congruence to nitrite binding to the CH 1-, 3-, and 5-posi-
À
tion three-point binding motif by means of the CH···A
effect, and to the hydroxyl group in position 2.
1
9
1
Figure 1. F and H NMR spectroscopic tests of compound 1b with
1
9
19
TBAF (0.3 equiv). a) F NMR spectroscopic test of TBAF. b) F NMR
1
spectroscopic test of compound 1b with TBAF. c) H NMR spectroscopic
test of compound 1b. d) H NMR spectroscopic test of compound 1b
1
with TBAF.
1
Table 3. Relative H shifts (Dd) of derivatives 7–11 in the presence and
absence of nitrite anions in [D]benzene.
Figure 2. Job plot of compound 7/nitrite. The maximum value of Dd*x is
at the 0.333 position on the x axis, which indicates exactly a carbohy-
drate/anion 1:2 complex.
Compound
DH1
DH2
DH3
DH4
DH5
DH6
a
DH6
b
7
8
9
1
1
0.90
0.64
0.70
0.24
0.40
0.32
0.36
0.41
0.00
0.15
0.46
0.39
0.26
0.22
0.45
0.17
0.06
0.00
0.50
0.60
0.50
0.42
0.36
0.35
0.90
0.1
0.09
0.34
0.00
1.00
0.60
0.23
0.04
0.90
0.50
More interestingly, it seemed that certain solvents also
gave rise to the supramolecular effect with carbohydrates
holding H1-, H3-, H5-cis pattern. Comparison of the H-
0
1
1
chemical shifts of compound 1b with and without nitrite
anions in deuterated solvents was thus performed (Table 4).
It was found that in DMF, acetonitrile, and chloroform, the
difference values of the proton shifts were close to negligi-
ble. In benzene, the difference values for the chemical shifts
1
9
d=70 ppm in an F NMR spectroscopy test and the chemi-
cal shift differences of H1, H3, and H5 shifted downfield by
d=0.23, 0.26, and 0.31 ppm in an H NMR spectroscopy test
1
(
Figure 1). These results indicated a strong effect
between compound 1b and fluoride anion.
Partially protected b-d-glycosides with one un-
protected hydroxyl group were also tested with ni-
trite anions in [D]benzene (Table 3). Although
a similar supramolecular effect could be observed
in these cases, the hydroxyl group affected the re-
sults to some extent. It is in this context reported
that hydrogen bonding can take place between
anions and carbohydrate hydroxyl groups in nonpo-
1
Table 4. Comparison of H chemical shifts of intermediate 1b before and after addi-
tion of nitrite anion in various deuterated solvents.
[
D]solvent
H1
H2
6.16
6.24
0.08
5.74
5.63
H3
H4
6.07
6.34
0.27
6.05
5.96
H5
H6
a
H6
b
[8c]
no nitrite
nitrite
Dd
benzene
benzene
4.11
4.93
0.82
4.67
4.68
0.01
4.85
4.94
0.09
5.20
5.25
0.05
5.10
6.13
1.03
5.23
5.30
0.07
5.60
5.78
0.18
6.21
6.28
0.07
3.42
4.56
1.14
4.22
4.26
0.04
4.40
4.52
0.12
4.85
4.91
0.06
4.22
4.41
0.19
4.41
4.32
4.58
4.69
0.11
4.66
4.54
lar solvents, an effect that explains the downfield
shifts of the 2-OH protons of compounds 7, 8, and
9
, the 6-OH proton of compound 10, and the 4-OH no nitrite
CDCl3
nitrite
Dd
CDCl
3
proton of compound 11, respectively. However, the
concurrent dramatic downfield shift of the H1, H3,
and H5 signals for all of these compounds can be
explained only by the carbohydrate–anion recogni- Dd
tion effect reported herein.
À0.09
À0.09
À0.09
À0.12
no nitrite
nitrite
CD
CD
3
3
CN
CN
5.60
6.04
4.42
4.55
5.57
6.03
4.41
4.52
À0.03
À0.01
À0.01
À0.03
no nitrite
nitrite
Dd
DMF
DMF
5.82
6.29
4.70
4.56
5.85
0.03
6.32
0.03
4.72
0.02
4.60
0.04
This explanation was subsequently supported by
H NMR spectroscopic titration experiments using
1
Chem. Asian J. 2014, 9, 1298 – 1304
1300 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Olof Ramstrçm, Hai Dong, and Bo Ren
of the 2-, 4-, and 6-protons remained small, whereas the
shifts for the protons in position 1, 3, and 5 were displaced
downfield by d=0.82, 1.03, and 1.14 ppm, respectively. Simi-
lar effects were observed for compounds 1a, 2a, and 2b, al-
though they were not observed for the 2- or 3-OTf (Tf=tri-
fluoromethanesulfonate) intermediate of a-galactoside.
Thus, these results indicate the formation of a carbohy-
drate–nitrite complex in benzene and provided a clue as to
than did the nitrite anions in benzene. For intermediate 2b,
the protons in positions 1, 3, and 5 shifted from d=3.96,
5.53, and 3.47 ppm in benzene to d=5.30, 6.10, and
4.85 ppm in DMF, which are slightly higher than the shift
values that result from nitrite in benzene (d=4.74, 5.97, and
4.35 ppm).
These results indicate that, similar to the nitrite ions, the
solvent molecules are also able to interact with the CH 1-,
3-, 5-position three-point binding motif to form van der
Waals or hydrogen-bond complexes (Figure 3). It has been
shown that carbohydrate/p interactions generally occur be-
tween H1, H3, and H5 protons of pyranosides and the ben-
[6]
how the reported supramolecular control occurred.
Interestingly, the same effect was found in comparison of
the proton chemical shifts in intermediates 1b and 2b in the
absence of nitrite anions in the various deuterated solvents.
The proton shift values in positions 1, 3, and 5 were general-
ly displaced to a lower field with an increase in solvent po-
larity. For example, for intermediate 1b (Figure 3), the pro-
tons in positions 1, 3, and 5, respectively, shifted from d=
[1c,j,5]
zene ring.
Thus, it is possible that, in the nonpolar sol-
vent benzene, complex a can form between compound 1b
and the benzene molecules by means of CH–p interactions,
although this type of interaction may be quite weak
(Figure 4). However, owing to the magnetic anisotropy of
4
4
.11, 5.10, and 3.42 ppm in benzene to d=4.67, 5.23, and
.22 ppm in chloroform; d=4.85, 5.60, and 4.40 ppm in ace-
tonitrile; d=4.96, 6.04, and 4.42 ppm in DMSO; and d=
.20, 6.21, and 4.85 ppm in DMF. The proton shifts in
5
DMSO were very similar to the deshielding results for ni-
trite in benzene (d=4.93, 6.15, and 4.56 ppm), which sug-
gests that the same interaction occurs between intermediate
1
b and DMSO as that between intermediate 1b and the ni-
trite anions. However, DMF resulted in higher shift values
1
Figure 4. Comparison of H-chemical shifts of compound 1b in C
various concentrations: a) 0.006, b) 0.025, c) 0.066m.
6 6
D in
benzene, protons H1, H3, and H5, may also experience ad-
ditional magnetic shielding in the complex. On the other
hand, the “real” chemical shift (without any shielding ef-
fects) of compound 1b d0 should be displaced downfield
compared to the “real” chemical shift of complex a. Since
a low concentration of compound 1b equates the formation
of a large proportion of complex a owing to equilibration,
the recorded chemical shifts of H1, H3, and H5 in high con-
centrations of 1b should become displaced downfield as
compared to the recorded chemical shifts at low concentra-
tions of 1b. The experiments support this (Figure 4), where
the recorded chemical shifts of H1, H3, and H5 were d=
4.13, 5.13, and 3.45 ppm for a 0.066m concentration, d=
4.12, 5.12, and 3.43 ppm for a 0.025m concentration, and d=
4.11, 5.10, and 3.42 ppm for a 0.006m concentration respec-
tively, thus indicating the equilibration between compound
1
b and complex a.
However, the downfield shifts of protons H1, H3, and H5
of this complex upon addition of certain entities, indicate
the dissociation of the carbohydrate/p complex. The carbo-
hydrate/new-entity association energy thus compensates for
1
Figure 3. Comparison of H chemical shifts of compound 1b in different
deuterated solvents and proposed 1b/solvent molecule complexes with
1
a) C
6
D
6
, b) CDCl
3
, c) CD
3
CN, d) [D
6
]DMSO, and e) [D
7
]DMF.
the carbohydrate/p dissociation energy. By H NMR spec-
Chem. Asian J. 2014, 9, 1298 – 1304
1301 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Olof Ramstrçm, Hai Dong, and Bo Ren
DMSO,
amounted to 1.87, 4.01, and
.67m, respectively, thus indi-
and
acetonitrile
0
cating the proposed 1b/solvent
molecule complexes. It also in-
dicated that these complexa-
tions were strengthened by the
hydrogen-bonding ability of the
solvents.
Scheme 3. Binding competition between the nitrite and solvent molecules.
troscopic titration experiments, the binding constant relative
to carbohydrate/p complex can be determined. Thus, after
the addition of relatively poorly solvated nitrite anions, the
benzene molecule was instantly displaced from complex a to
form a carbohydrate-nitrite complex (Scheme 3). In the
polar solvents chloroform, acetonitrile, DMF, and DMSO,
complexes b–e can form between compound 1b and the sol-
vent molecules through van der Waals interactions or weak
hydrogen bonds. In these cases, the nitrite anions are also
more efficiently solvated, resulting in lower concentrations
of carbohydrate–nitrite complexes. Thus, these effects for ni-
trite were found only in the nonpolar solvents toluene and
benzene because of binding competition between the nitrite
and solvent molecules (Scheme 3).
Conclusion
This study reports the evaluation of a carbohydrate–anion
system, in which complexes form between anions and pyra-
noside B-faces through an H1-, H3-, H5-cis pattern. Com-
plexation is likely derived from van der Waals interactions
À
or weak CH···A hydrogen bonds between the species, and
may be strengthened by electron-withdrawing groups of the
carbohydrates and the hydrogen-bonding ability of the
anions. This novel host–guest system represents a general
effect for pyranoside–anion recognition, which can be ap-
plied to a wide range of similar systems.
1
H NMR spectroscopic titration experiments using com-
pound 1b and various solvents in benzene were also per-
formed (Figure 5). The association constant of DMF,
Experimental Section
General
All commercially available starting materials and solvents were reagent-
grade and used without further purification. H NMR were recorded with
1
a 400 or 500 MHz or instrument at 298 K in C
6
D
6
, CDCl
3
, CD
3
CN,
( H: d=
CN ( H: d=1.94 ppm),
1
[
7
D
6
]DMSO and [D
7
]DMF using the residual signals from C D
6 6
1
1
.16 ppm), CHCl
3
( H: d=7.25 ppm), CD
3
1
1
[
D
6
]DMSO ( H: d=2.50 ppm) and [D
7
]DMF ( H: d=8.03 ppm) as inter-
1
nal standards. H peak assignments were made by first-order analysis of
the spectra, supported by standard H, H correlation spectroscopy
COSY).
1
1
(
General NMR Spectroscopic Analysis Experiments
Carbohydrates (1–3 mg) and TBA salts of the anions (10–20 equiv) were
dissolved in deuterated solvents (0.5 mL). The proton shifts were record-
ed, and the proton peak assignments were made by first-order analysis of
1
1
the spectra, supported by standard H, H COSY.
[
9]
Binding Analysis
Compound 7 (2.5 mg) and different amounts of TBA nitrite were dis-
solved in deuterated benzene (0.5 mL). The proton shifts were recorded,
and the proton peak assignments were made by first-order analysis of the
1
1
spectra, supported by standard H, H COSY.
Methyl-2,4,6-tri-O-acetyl-3-O-triflate-b-d-galactoside (1a)
[
10]
The compound was acquired by triflation of methyl 2,4,6-tri-O-acetyl-
[
11] 1
b-d-galactoside.
.7 Hz, J(H2,H3)=10.0 Hz, 1H; H2), 5.52 (d, J
H4), 4.75 (dd, J(H3,H2)=10.0 Hz, J(H3,H4)=3.5 Hz, 1H; H3), 4.08 (dd,
(H6 ,H5)=7.0 Hz, (H6 ,H6 )=11.2 Hz, 1H; H6 ), 4.00 (dd, J-
(H6 ,H5)=6.5 Hz, J(H6 ,H6 )=11.2 Hz, 1H; H6 ), 3.87 (d, J(H1,H2)=
.7 Hz, 1H; H1), 3.16 (s, 3H; OMe), 3.04–3.08 (m, 1H; H5), 1.79 (s, 3H;
H NMR (C
6
D
6
, 500 MHz): d=5.67 (dd, J
ACHTUNGTRENNUNG( H2,H1)=
8
A
H
U
G
R
N
U
G
ACHTUNGTR(NENNUG H4,H3)=3.5 Hz, 1H;
A
H
U
G
R
N
U
G
ACHTUNGTRENNUNG
J
A
H
U
G
R
N
U
G
a
J
A
H
U
G
R
N
U
G
a
b
a
A
T
N
R
N
N
b
A
H
U
G
R
N
N
b
a
b
ACHTUNGTRENNUNG
8
OAc), 1.64 (s, 3H; OAc), 1.41 ppm (s, 3H; OAc).
Figure 5. NMR spectroscopic titration for compound 1b with a) DMF,
2
b) DMSO, and c) acetonitrile in benzene. For DMF, K=1.87m, R =
2
1
.000; for DMSO, K=4.01m, R =1.000; and for acetonitrile, K=0.67m,
2
R =0.998.
Chem. Asian J. 2014, 9, 1298 – 1304
1302 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Olof Ramstrçm, Hai Dong, and Bo Ren
Methyl-2,4,6-tri-O-benzoyl-3-O-triflate-b-d-galactoside (1b)
1H; H6
b
), 4.29 (d, J ACHTUNTGENRNUG( H1,H2)=7.8 Hz, 1H; H1), 3.79–3.86 (m, 1H; H5),
3
.18 (s, 3H; OMe), 1.57 ppm (s, 3H; SAc).
[
10]
The compound was acquired by triflation of methyl 2,4,6-tri-O-benzo-
[
11] 1
yl-b-d-galactoside.
OBz), 6.81–7.14 (m, 9H; OBz), 6.16 (dd, J
0.3 Hz, 1H; H2), 6.07 (d, J(H4,H3)=3.5 Hz, 1H; H4), 5.10 (dd, J-
(H3,H2)=10.0 Hz, J(H3,H4)=3.5 Hz, 1H; H3), 4.58 (dd, J(H6 ,H5)=
.8 Hz, J(H6 ,H6 )=11.2 Hz, 1H; H6 ), 4.22 (dd, J(H6 ,H5)=6.2 Hz, J-
(H6 ,H6 )=11.2 Hz, 1H; H6 ), 4.11 (d, J(H1,H2)=7.8 Hz, 1H; H1), 3.42
t, J(H5,H6)=6.8 Hz, 1H; H5), 3.20 ppm (s, 3H; OMe).
H NMR (C
6
D
6
, 500 MHz): d=8.01–8.18 (m, 6H;
Methyl-3,4,6-tri-O-benzoyl-b-d-galactoside (7)
A
H
U
G
E
N
N
ACHTUNGTRENNUNG
[
13]
The compound was synthesized by organotin multiple benzoylation.
1
ACHTUNGTRENNUNG
1
H NMR (C
6
D
6
, 500 MHz): d=7.87–8.15 (m, 6H; OBz), 6.82–7.14 (m,
H; OBz), 5.91 (d, J(H4,H3)=3.5 Hz, 1H; H4), 5.33 (m, J(H3,H2)=
0.1 Hz, J(H3,H4)=3.5 Hz, 1H; H3), 4.61 (dd, J(H6 ,H5)=7.0 Hz, J-
,H6 )=11.3 Hz, 1H; H6 ), 4.18 (dd, (H6 ,H5)=6.6 Hz, J-
,H6 )=11.3 Hz, 1H; H6 ), 4.02–4.10 (m; 1H, H2), 3.92 (d, J-
(H1,H2)=7.6 Hz, 1H; H1), 3.49 (t, J(H5,H6)=7.0 Hz, 1H; H5), 3.29 (s,
H; OMe), 1.92 ppm (s, 1H; OH).
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
H
U
T
E
N
N
a
9
1
A
H
U
G
R
N
N
ACHTUNGTRENNUNG
6
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
b
a
A
H
U
G
R
N
U
G
b
A
H
U
G
R
N
N
A
H
U
G
E
N
N
a
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
b
a
b
ACHTUNGTRENNUNG
A
H
U
G
R
N
N
a
b
a
J
A
T
G
E
N
N
b
(
ACHTUNGTRENNUNG
A
H
U
T
E
N
G
b
a
b
Methyl-3,4,6-tri-O-acetyl-2-O-triflate-b-d-galactoside (2a)
A
H
U
T
E
U
G
ACHTUNGTRENNUNG
3
[
10]
The compound was acquired by triflation of methyl 3,4,6-tri-O-acetyl-
[
11] 1
b-d-galactoside.
.5 Hz, 1H; H4), 5.00 (dd, J
H3), 4.93 (dd, J(H2,H1)=7.6 Hz, J
m, 2H; H6), 3.79 (d, J(H1,H2)=7.6 Hz, 1H; H1), 3.3 (t, J
.8 Hz, 1H; H5), 3.21 (s, 3H; OMe), 1.78 (s, 3H; OAc), 1.65 (s, 3H;
H NMR (C
(H3,H2)=10.5 Hz, J
(H2,H3)=10.5 Hz, 1H; H2), 3.94–4.03
(H5,H6)=
6
D
6
, 500 MHz): d=5.37 (d, J
A
H
U
G
R
N
U
G
Methyl-3,4,6-tri-O-benzoyl-b-d-taloside (8)
3
A
H
U
G
R
N
U
G
ACHTUNGTR(NENNUG H3,H4)=3.5 Hz, 1H;
[
13] 1
The compound was acquired by inversion of compound 7.
H NMR
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ACHTUNGTRENNUNG
(
5
3
H6
(
C
6
D
6
, 500 MHz): d=8.01–8.15 (m, 6H; OBz), 6.87–7.17 (m, 9H; OBz),
.84 (d, J(H4,H3)=3.5 Hz, 1H; H4), 4.93 (t, J(H2,H3), J(H3,H4)=
.5 Hz, 1H; H3), 4.77 (dd, J(H6 ,H5)=7.3 Hz, J(H6 ,H6 )=11.4 Hz, 1H;
), 4.62 (dd, J(H6 ,H5)=5.2 Hz, J(H6 ,H6 )=11.4 Hz, 1H; H6 ), 3.96
d, J(H2,OH)=12.0 Hz, 1H; H2), 3.84 (s, 1H; H1), 3.35–3.40 (m, 1H;
H5), 3.18 (s, 3H; OMe), 2.92 ppm (d, J(OH,H2)=12.0 Hz, 1H; OH).
(
A
H
U
G
R
N
U
G
ACHTUNGTRENNUNG
A
H
N
T
N
N
A
H
N
T
E
N
N
ACHTUNGTRENNUNG
6
A
H
U
G
R
N
U
G
a
A
H
U
G
R
N
U
G
a
b
OAc), 1.55 ppm (s, 3H; OAc).
a
A
H
U
G
R
N
U
G
b
A
H
U
G
R
N
N
b
a
b
ACHTUNGTRENNUNG
Methyl-3,4,6-tri-O-benzoyl-2-O-triflate-b-d-galactoside (2b)
AHCTUNGTRENNUNG
[
10]
The compound was acquired by general triflation of methyl 3,4,6-tri-O-
[
11]
1
Methyl-3,4,6-tri-O-benzoyl-b-d-glucoside (9)
benzoyl-b-d-galactoside.
H NMR (C
H; OBz), 6.80–7.14 (m, 9H; OBz), 6.07 (d, J
.53 (dd, J(H3,H2)=10.3 Hz, J(H3,H4)=3.5 Hz, 1H; H3), 5.42 (dd, J-
(H2,H3)=10.3 Hz, 1H; H2), 4.58 (dd, J(H6 ,H5)=
)=11.3 Hz, 1H; H6 ), 4.14 (dd, J(H6 ,H5)=6.5 Hz, J-
)=11.3 Hz, 1H; H6 ), 3.96 (d, J(H1,H2)=7.7 Hz, 1H; H1), 3.47
(H5,H6)=6.5 Hz, 1H; H5), 3.22 ppm (s, 3H; OMe).
6
D
6
, 500 MHz): d=7.93–8.16 (m,
6
5
A
H
U
G
R
N
U
G
[13]
The compound was synthesized by organotin multiple benzoylation.
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
H
U
G
R
N
U
G
1
H NMR (C
H; OBz), 5.62–5.72 (m, 2H; H3, H4), 4.54 (dd, J
(H6 ,H6 )=12.0 Hz, 1H; H6 ), 4.34 (dd, (H6
(H6 ,H6 )=12.0 Hz, 1H; H6 ), 3.91 (d, J(H1,H2)=7.4 Hz, 1H; H1), 3.60
b, 1H; H2), 3.46 (b, 1H; H5), 3.24 ppm (s, 3H; OMe).
6
D
6
, 500 MHz): d=7.94–8.14 (m, 6H; OBz), 6.84–7.14 (m,
(H6 ,H5)=3.2 Hz, J-
,H5)=6.0 Hz, J-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
(H2,H1)=7.7 Hz, J
.8 Hz, J(H6 ,H6
(H6 ,H6
t, J
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
H
U
G
R
N
U
G
a
9
A
H
U
G
R
N
U
a
6
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
b
a
A
H
U
G
R
N
U
G
b
A
H
U
G
E
N
N
a
b
a
J
A
H
U
G
E
N
N
b
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
b
a
b
ACHTUNGTRENNUNG
A
H
N
R
N
U
G
b
a
b
ACHTUNGTRENNUNG
(
ACHTUNGTRENNUNG
(
Methyl-2,3,4,6-tetra-O-acetyl-b-d-galactoside (3)
The compound was acquired by the general acetylation procedure using
Methyl-2,3,4-tri-O-benzoyl-b-d-galactoside (10)
The compound was acquired by removing the 6-TIPS (triisopropylsilyl)
group of methyl 2,3,4-tri-O-benzoyl-6-O-triisopropylsilyl-b-d-galactoside,
1
acetic anhydride/pyridine. H NMR (C
(H2,H1)=7.9 Hz, J(H2,H3)=10.3 Hz, 1H; H2), 5.55 (d, J
.7 Hz, 1H; H4), 4.83 (dd, J(H3,H2)=10.3 Hz, J(H3,H4)=3.7 Hz, 1H;
H3), 4.10 (dd, J(H6 ,H5)=6.8 Hz, J(H6 ,H6 )=11.3 Hz, 1H; H6 ), 4.02
dd, (H6 ,H5)=6.8 Hz, (H6 ,H6 )=11.3 Hz, 1H; H6 ), 3.94 (d, J-
(H1,H2)=7.9 Hz, 1H; H1), 3.18 (s, 3H; OMe), 3.14–3.19 (m, 1H; H5),
.79 (s, 3H; OAc), 1.65 (s, 3H; OAc), 1.42 ppm (s, 6H; 2XOAc).
6
D
6
, 500 MHz): d=5.68 (dd, J-
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
H
U
G
R
N
U
G
[10a,13]
which was synthesized using methods found in the literature.
3
A
H
U
G
R
N
U
G
A
H
U
G
R
N
U
1
H NMR (C
6
D
6
, 500 MHz): d=8.00–8.16 (m, 6H; OBz), 6.70–7.01 (m,
H; OBz), 6.30 (dd, J(H2,H1)=8.0 Hz, J(H2,H3)=10.5 Hz, 1H; H2),
.97 (d, J(H4,H3)=3.5 Hz, 1H; H4), 5.68 (dd, J(H3,H2)=10.5 Hz, J-
(H1,H2)=8.0 Hz, 1H; H1), 3.67
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
A
T
N
T
E
N
N
a
b
a
9
5
A
H
U
G
R
N
U
G
ACHTUNGTRENNUNG
(
J
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
b
J
A
H
U
G
R
N
U
G
b
a
b
A
H
U
G
R
N
U
G
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
A
H
U
G
R
N
N
ACHTUNGTRENNUNG
1
(
A
H
U
G
R
N
U
G
a
A
H
U
G
R
N
U
G
a
b
a
), 3.44–3.53 (m,
2
b
Methyl-2,3,6-tri-O-acetyl-4-fluoride-b-d-galactoside (4)
Methyl-2,3,6-tri-O-acetyl-b-d-glucoside (11)
The compound was synthesized by organotin multiple acetylation.
The compound was synthesized using methods found in the litera-
[
11, 12] 1
ture.
(H2,H3)=10.0 Hz, 1H; H2), 4.96 (dd, 1H;
(H3,F4)=30 Hz, H3), 4.58 (d, J(H4,F4)=52.8 Hz, 1H; H4), 4.33 (dd, J-
(H6 ,H5)=6.7 Hz, J(H6 ,H6 )=11.2 Hz, 1H; H6 ), 4.08–4.15 (dd, 1H;
H6 ), 4.11 (d, J(H1,H2)=9.0 Hz, 1H; H1), 3.21 (s, 3H; OMe), 3.12–3.22
m, 1H; H5), 1.71 (s, 3H; OAc), 1.63 (s, 3H; OAc), 1.59 ppm (s, 3H;
H NMR (C
6
D
6
, 500 MHz): d=5.73 (dd, J
A
H
U
G
R
N
U
G
[13]
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
J
A
H
U
G
R
N
U
G
1
H NMR (C
.2 Hz, 1H; H2), 5.21 (t, J
(H6 ,H5)=4.3 Hz, J(H6 ,H6 )=12.0 Hz, 1H; H6
H6 ), 4.14 (d, 1H; J(H1,H2)=8.0 Hz, H1), 3.40–3.50 (b, 1H; H4), 3.21 (s,
H; OMe), 2.99–3.08 (m, 1H; H5), 1.74 (s, 3H; OAc), 1.73 (s, 3H;
OAc), 1.60 ppm (s, 3H; OAc).
6
D
6
, 500 MHz): d=5.26 (dd, J
(H3,H2)=9.2 Hz, 1H; H3), 4.32 (dd, J-
), 4.11–4.20 (dd, 1H;
ACTHUNGTRENNUNG( H2,H1)=8.0 Hz, J ACHTUNGTRENNUNG( H2,H3)=
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ACHTUNGTRENNUNG
9
ACHTUNGTRENNUNG
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
b
a
A
H
U
G
R
N
U
G
a
A
H
U
G
R
N
U
G
a
b
a
b
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
b
(
3
OAc).
Methyl-2,3,4,6-tetra-O-benzoyl-b-d-galactoside (5)
The compound was acquired by the general benzoylation procedure
1
using benzoyl chloride/pyridine. H NMR (C
(
6
D
6
, 500 MHz): d=7.96–8.24
(H2,H1)=8.0 Hz, J-
(H4,H3)=3.5 Hz, 1H; H4), 5.75
(H3,H4)=3.5 Hz, 1H; H3), 4.73 (dd, J-
,H6 )=10.2 Hz, 1H; H6 ), 4.38 (d, J(H1,H2)=
.0 Hz, 1H; H1), 4.31 (dd, J(H6 ,H5)=6.6 Hz, J(H6 ,H6 )=11.3 Hz, 1H;
H6 ), 3.73 (t, J(H5,H6)=6.6 Hz, 1H; H5), 3.25 (s, 3H; OMe), 1.57 ppm
s, 3H; OAc).
m, 8H; OBz), 6.68–7.13 (m, 12H; OBz), 6.33 (dd, J
(H2,H3)=10.4 Hz, 1H; H2), 6.20 (d, J
dd, (H3,H2)=10.4 Hz,
(H6 ,H5)=6.6 Hz, J(H6
A
H
U
G
R
N
U
G
Acknowledgements
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ACHTUNGTRENNUNG
(
J
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
JACHTUNGTRENNUNG
This study was supported by the National Nature Science Foundation of
China (nos. 21272083), the Chutian Project-Sponsored by Hubei Province
and the Swedish Research Council. The authors are also grateful to the
staff of the Analytical and Test Center of HUST for support with the
NMR instruments.
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
a
b
a
ACHTUNGTRENNUNG
8
A
H
U
G
R
N
U
G
b
A
H
U
G
R
N
N
b
a
b
ACHTUNGTRENNUNG
(
Methyl-2,3,6-tri-O-benzoyl-4-S-acetyl-b-d-galactoside (6)
The compound was synthesized using methods found in the litera-
[1] a) J. L. Asensio, A. Arda, F. J. Canada, J. Jimenez-Barbero, Acc.
Chem. Res. 2013, 46, 946–954; b) A. G. Santana, E. Jimenez-
Moreno, A. M. Gomez, F. Corzana, C. Gonzalez, G. Jimenez-Oses,
J. Jimenez-Barbero, J. L. Asensio, J. Am. Chem. Soc. 2013, 135,
3347–3350; c) S. Kozmon, R. Matuska, V. Spiwok, J. Koca, Chem.
Eur. J. 2011, 17, 5680–5690; d) R. Lucas, I. Gomez-Pinto, A. Avino,
[
11, 12] 1
ture.
.13 (m, 9H; OBz), 5.98 (dd, J
H2), 5.79 (dd, J(H3,H2)=10.0 Hz, J
(H4,H3)=4.5 Hz, 1H; H4), 4.74 (dd, J
1.3 Hz, 1H; H6 ), 4.35 (dd, J(H6 ,H5)=5.8 Hz, J
H NMR (C
6
D
6
, 500 MHz): d=8.07–8.27 (m, 6H; OBz), 6.84–
(H2,H1)=7.8 Hz, J(H2,H3)=10.0 Hz, 1H;
(H3,H4)=4.5 Hz, 1H; H3), 4.86 (d,
(H6 ,H5)=7.0 Hz, J(H6 ,H6 )=
(H6 ,H6 )=11.3 Hz,
7
A
H
U
G
R
N
U
G
ACHTUNGTRENNUNG
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
ACHTUNGTRENNUNG
J
A
C
H
T
U
N
G
T
R
E
N
N
U
N
G
A
H
U
G
E
N
N
a
A
T
N
T
E
U
G
a
b
1
a
A
H
U
G
E
N
N
b
A
H
U
T
E
N
G
b
Chem. Asian J. 2014, 9, 1298 – 1304
1303 ꢀ 2014 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

www.chemasianj.org
Olof Ramstrçm, Hai Dong, and Bo Ren
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