New class of quaternary ammonium salts, derivatives of methyl D-glucopyranosides

Article abstract of DOI:10.1016/j.carres.2004.03.013

Reactions of two aromatic and two aliphatic amines with methyl 6-O-p-toluenesulfonyl-α-D-glucopyranoside or methyl 6-O-p-toluenesulfonyl- β-D-glucopyranoside were performed on a micro-scale. The synthesis and preparative isolation methods have been develo

Full text of DOI:10.1016/j.carres.2004.03.013

Carbohydrate
RESEARCH
Carbohydrate Research 339 (2004) 1537–1544
New class of quaternary ammonium salts, derivatives of methyl
-glucopyranosidesq
D
Lucyna Pellowska-Januszek,a Barbara Dmochowska,a,* Eugenia Skorupa,a
b
Jarosław Chojnacki, Wiesław Wojnowski and Andrzej Wisniewski
b
a
ꢀ
aDepartment of Chemistry, University of Gdaꢀnsk, 18 Sobieskiego, PL-80-952 Gdaꢀnsk, Poland
bDepartment of Inorganic Chemistry, Technical University of Gdaꢀnsk, 11/12 G. Narutowicza, PL-80-952 Gdaꢀnsk, Poland
Received 19 January 2004; accepted 8 March 2004
Abstract—Reactions of two aromatic and two aliphatic amines with methyl 6-O-p-toluenesulfonyl-a-
6-O-p-toluenesulfonyl-b- -glucopyranoside were performed on a micro-scale. The synthesis and preparative isolation methods have
been developed for quaternary N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-a- and -b- -glucopyranoside-6-yl)ammonium salts derived
from three amines: trimethylamine, 2-methylpyridine, and pyridine. The reaction products were examined with 1H, 13C NMR
D-glucopyranoside or methyl
D
D
spectroscopy. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-b-D-glucopyranoside-6-yl)trimethylammonium tosylate was additionally ana-
lyzed with X-ray crystallography.
ꢀ 2004 Elsevier Ltd. All rights reserved.
Keywords: Quaternary ammonium salt; Methyl glucopyranoside; 1H, 13C NMR spectroscopy; X-Ray crystallography
1. Introduction
reaction with tertiary amine giving the appropriate
quaternary salts with the new N–Can bond. Fischer and
Quaternary ammonium salts (quats) constitute a huge
group of organic compounds. N-Substituted salts of
pyridine and related compounds constitute the most
important and versatile investigated products of chem-
ical syntheses.1;2 Menschutkin3 in 1890 reported first
preparations of quaternary ammonium salts by the
reaction of an alkyl halide with a tertiary amine. This
reaction, named the Menschutkin reaction, is the most
convenient method for synthesis of these compounds
(QACs). In contrast to the large body of literature on
the N-alkylated (arylated) salts of pyridine and related
compounds, two dozen or so papers are found in the
literature on the N-glycosylated analogues, only. Per-O-
acetyl-glycopyranosyl halides (mostly bromides and
chlorides), as well as methyl iodide, offer a possibility of
Raske4 in 1910 first reported the synthesis of N-(tetra-O-
acetyl-D-glucopyranosyl)pyridinium bromide, but its
structure was elucidated only from the elemental anal-
ysis. Their work was continued by Karrer and co-
workers,5;6 and structures of the compounds were also
insufficiently documented. Lemieux and Morgan in 1963
identified two anomers of N-(tetra-O-acetyl-D-gluco-
pyranosyl)pyridinium bromide in the reaction mixture
for which the structures were exhaustively documented,7
and a simplified mechanism of their formation was
proposed.7;8 Every product of the reaction formed a
conformational equilibrium mixture.
Lemieux discovered the reverse anomeric effect,9
which prefers the equatorial orientation of an aglycone
in molecules with C-1–Nþ bond. He studied an influence
of the reactant concentration and the presence of phenol
or tetra-n-butylammonium bromide or tetra-n-butyl-
ammonium perchlorate on the mutual concentration of
qPart 1 in the series ‘Quaternary ammonium salts, derivatives of
monosaccharides’.
the a and b anomer of N-(tetra-O-acetyl-D-glucopyr-
anosyl)pyridinium bromide in the post-reaction mixture.
The above-mentioned influence of phenol addition was
* Corresponding author. Tel.: +48-58-341-52-71; fax: +48-58-345-04-
72; e-mail: bdmochow@chemik.chem.univ.gda.pl
0008-6215/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2004.03.013

1538
L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
reported earlier by Fischer and Raske.4 Sinnott and
co-workers10–13 studied, inter alia, enzymatic hydrolysis
of the O-deacetylated analogous salt. The authors
used the Lemieux14 procedure for O-deacetylation of N-
(per-O-acetyl-glycopyranosyl)pyridinium salts. Paulsen
et al.15 and Finch and Nagpurkar16 studied conforma-
tional equilibria of N-(per-O-acetyl-aldopyranosyl)pyri-
1
dinium and -imidazolium salts with H NMR spectro-
scopy, and the reverse anomeric effect was discussed.
However, Abel et al.17 reported the effectiveness of
modified surfaces for antibacterial activity against a
series of seven Gram-positive and Gram-negative bac-
teria. In that paper authors demonstrated that broad
antibacterial activity can be imported to carbohydrate
surfaces through the covalent attachment of cationic
agents with lipophilic adjuncts. First, they functional-
ized primary hydroxyl group with p-toluenesulfonyl
chloride.
The purpose of the present contribution is to synthesize
and determine the structure of some quaternary ammo-
nium salts. Another purpose is to study their biological
activities in order to select antibacterial compounds that
are not harmful to humans and the environment.
2. Results and discussion
In recent years our research group has worked on the
formation of quaternary N-(D-glycopyranosyl)ammo-
nium salts.18–21 We thought that QACs with a sugar
moiety could be very interesting and promising kind of
compounds. We determined their chemical and crystal
structures. Some of them exhibit biological activity.
The synthesis of N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-a-
D
-glucopyranoside-6-yl)ammonium tosylate and N-(me-
thyl 2,3,4-tri-O-acetyl-6-deoxy-b- -glucopyranoside-6-yl)-
ammonium tosylate started from commercially available
methyl a- -glucopyranoside and methyl b- -glucopyr-
anoside, respectively. The selective esterification of the
primary hydroxyl groups of methyl -glucopyranoside with
p-toluenesulfonyl chloride in pyridine has been described.22
Reaction methyl 6-O-tosyl- -glucopyranosides with
D
D
D
D
D
trimethylamine, 2-methylpyridine or pyridine gave quater-
nary salts, demonstrating that the amines were effective
nucleophilic reagents. All new synthesized N-(methyl 2,3,
4-tri-O-acetyl-6-deoxy-D-glucopyranoside-6-yl)ammonium-
tosylates are water soluble. The structures were deter-
1
mined by 2D H NMR (400 MHz). The chemical shifts
and coupling constants for N-(methyl 2,3,4-tri-O-acetyl-
6-deoxy-
protons are listed in Table 1.
Reaction of methyl a- -glucopyranoside (1a) with p-
D-glucopyranoside-6-yl)-ammonium tosylate
D
toluenesulfonyl chloride in pyridine (Scheme 1) for 24 h
at rt afforded, after conventional processing, methyl 6-
O-p-toluenesulfonyl-a-D-glucopyranoside (2a) in 45%
20
D
yield; ½aŠ 73.1 (EtOH). In the same procedure methyl

L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
1539
Scheme 1. Reagents and conditions: (i) TsCl, pyridine; (ii) Me3N in 33% EtOH (compounds 3a and 3b), pyridine (compounds 4a and 4b),
2-methylpyridine (compounds 5a and 5b); (iii) Ac2O, pyridine. Ts ¼ p-toluenesulfonyl.
6-O-p-toluenesulfonyl-b-D-glucopyranoside (2b) was
Table 2. Crystal data and structure refinement for N-(methyl 2,3,4-tri-
O-acetyl-6-deoxy-b-D-glucopyranoside-6-yl)trimethylammonium tos-
ylate (3b)
obtained. Both of these esters (2a and 2b) are stable for
several months if kept at 0 °C. The next steps were the
quaternization reactions of 2a and 2b.
Reaction of 2a with 33% ethanolic solution of tri-
methylamine at 70 °C for 96 h produced, after O-acetyl-
Empirical formula
Formula weight
Temperature (K)
C23H35NO11
533.58
200(2)
S
ꢁ
Wavelength (A)
0.71073
Orthorhombic, P212121
ation (O-Ac), N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-a-D-
glucopyranoside-6-yl)trimethylammonium tosylate (3a)
Crystal system, space group
Unit cell dimensions
ꢁ
a (A)
8.859(2)
9.120(2)
34.465(7)
2784.6(10)
4
in 19% yield. The same reaction in ultrasonic conditions
at rt for 20 h gave 3a in 42% yield; ½aŠ20 92.46 (c 0.3, H2O).
ꢁ
b (A)
D
ꢁ
c (A)
Volume (A )
Under similar conditions (ultrasonic conditions, rt, 20 h)
N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-b-D-glucopyrano-
side-6-yl)trimethylammonium tosylate (3b) in 33% yield;
3
ꢁ
Z
Calculated density (Mg mÀ3
Absorption coefficient (mmÀ1
F ð000Þ
)
1.273
0.172
20
D
)
mp 210–220 °C; ½aŠ )2.28 (c 0.175, H2O) was obtained.
Their identities were confirmed by the 1H NMR and 13
NMR spectra evidence and X-ray diffraction for com-
C
1136
0.40 · 0.30 · 0.30
Crystal size (mm)
Theta range for data collection (°) 1:18 < h < 26:00
pound 3b (Tables 2–5; Figs. 1 and 2).
1
In the H NMR spectrum for compound 3a, the sig-
Index ranges, h, k, l
)6 fi 10, )11 fi 6, )28 fi 42
3205/3177
Reflections collected/unique
Reflections [I > 2rðIÞ]
Completeness to h ¼ 27:55
Refinement method
1655
0.993
nal for the anomeric proton is a doublet at d ¼ 5:13 ppm
with coupling constant of J1;2 ¼ 3:6 Hz, which is char-
acteristic for He–Ha. The chemical shift for H-2 is a
triplet at d ¼ 5:25 ppm with a coupling constant of
J2;3 ¼ 9:6 Hz. Signals of protons for H-3 and H-4 are at
d ¼ 5:09 ppm and d ¼ 5:04 ppm, respectively. Coupling
constants of J2;3, J3;4 and J4;5 at about 9.5 Hz are char-
acteristic for Ha–Ha system. The structure of the sugar
protons and values of coupling constants for H-1, H-2,
H-4 allows one to assert that the pyranose ring for
Full-matrix least-squares
refinement based on F 2
3177/0/334
Data/restraints/parameters
Goodness-of-fit on F 2
0.977
Final R indices [I > 2rðIÞ]
R1 ¼ 0.066, wR2 ¼ 0.1905
R1 ¼ 0.1874, wR2 ¼ 0.2751
0.0(4)
R indices (all data)
Absolute structure parameter
Largest difference peak and hole
À3
0.407/)0.438
ꢁ
(e A
)
4
compound 3a is in the C1 conformation.
In the spectrum of 3b compound, H-1 appears as a
doublet with a J1;2 ¼ 8:0 Hz (Ha–Ha). We found
coupling constants J2;3, J3;4 and J4;5 to be 9.4, 9.2,
8.0 Hz, respectively. The pyranose ring for compound 3b
In the crystal asymmetric unit of N-(methyl 2,3,4-tri-
O-acetyl-6-deoxy-b- -glucopyranoside-6-yl)trimethyl-
D
ammonium tosylate (3b) contains one ammonium cation
and one tosylate anion (see Fig. 1). The intermolecular
interactions between these ion pairs are shown in the
drawing of the elemental cell (Fig. 2). Several C–HÁ Á ÁO
short contacts are formed. Most of them can be regarded
as charge-assisted hydrogen bonds between C–H donors
from positively charged trimethylammonium groups and
4
is thus in the C1 conformation. The chemical shifts are
given in Table 1, the sequence of protons of compound
3a (H-2, H-1, H-3, H-4, H-5, H-6a, H-6b) are different
from compound 3b (H-2, H-3, H-4, H-1, H-5, H-6a,
H-6b).

1540
L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
ꢁ
Table 4. Selected bond lengths (A) for N-(methyl 2,3,4-tri-O-acetyl-6-
Table 3. Atomic coordinates and equivalent isotropic displacement
2
ꢁ
parameters (A ) for N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-b-
D
-gluco-
deoxy-b-
D
-glucopyranoside-6-yl)trimethylammonium tosylate
Bond length
pyranoside-6-yl)trimethylammonium tosylatea
x
y
z
Ueq
O-1–C-5
O-1–C-1
C-1–O-7
C-1–C-2
C-2–O-8
C-2–C-3
C-3–O-9
C-3–C-4
C-4–O-10
C-4–C-5
C-5–C-6
C-6–N-1
C-7–O-7
C-8–O-81
C-8–O-8
C-8–C-81
C-9–O-91
C-9–O-9
C-9–C-91
C-10–O-11
C-10–O-11
C-10–O-10
C-10–C-12
N-1–C-22
N-1–C-21
N-1–C-23
S-1–O-22
S-1–O-20
S-1–O-21
1.412(9)
S-1
0.7876(3)
0.6666(7)
0.9270(7)
0.8017(12)
0.6023(16)
0.6496(11)
0.652(2)
0.5690(3)
0.5766(8)
0.5220(9)
0.7004(9)
0.0886(18)
0.2140(16)
0.181(2)
0.06579(7)
0.03830(19)
0.0482(2)
0.0875(3)
0.1772(4)
0.1498(3)
0.1099(5)
0.0856(4)
0.0986(3)
0.1370(3)
0.1619(4)
0.08232(16)
0.0903(3)
0.1312(2)
0.1596(2)
0.1476(2)
0.0924(2)
0.0270(3)
0.06480(19)
0.1469(3)
0.14085(19)
0.1567(3)
0.1432(2)
0.2273(3)
0.19625(16)
0.2592(3)
0.2286(2)
0.1978(3)
0.17413(17)
0.2076(5)
0.1856(6)
0.2237(3)
0.0551(2)
0.0215(2)
0.0562(3)
0.0478(3)
0.0483(6)
0.0560(18)
0.062(2)
0.095(3)
0.096(5)
0.065(3)
0.133(8)
0.125(7)
0.055(3)
0.065(3)
0.090(4)
0.0422(14)
0.045(2)
0.0391(19)
0.0384(19)
0.0351(18)
0.0340(18)
0.098(5)
0.0590(18)
0.052(3)
0.0450(16)
0.069(3)
0.065(2)
0.055(3)
0.0440(15)
0.065(3)
0.098(3)
0.077(4)
0.0430(15)
0.086(7)
0.070(8)
0.071(3)
0.0385(16)
0.045(2)
0.048(2)
0.051(3)
1.435(10)
1.375(11)
1.504(12)
1.455(10)
1.479(12)
1.458(9)
O-20
O-21
O-22
C-50
C-51
C-52
C-53
C-54
C-55
C-56
O-1
1.509(12)
1.452(10)
1.521(11)
1.507(11)
1.496(10)
1.390(13)
1.200(12)
1.344(11)
1.502(15)
1.188(12)
1.337(11)
1.492(14)
1.320(2)
0.692(2)
0.2919(18)
0.4264(13)
0.4537(13)
0.3428(16)
0.4236(6)
0.3058(9)
0.2547(9)
0.3760(9)
0.5047(9)
0.6684(9)
0.2227(14)
0.1937(6)
0.0085(10)
0.1481(6)
)0.0849(12)
)0.0332(7)
0.3197(11)
0.3145(7)
0.2268(13)
0.3905(12)
0.6720(16)
0.6246(6)
0.582(2)
0.7348(10)
0.7364(13)
0.6985(17)
0.2700(7)
0.1672(11)
0.1954(10)
0.1856(10)
0.2822(10)
0.3473(9)
0.153(2)
C-1
C-2
C-3
C-4
C-6
C-7
O-7
C-8
0.1980(9)
0.1217(13)
0.0791(7)
1.307(17)
1.297(12)
1.439(15)
1.498(11)
1.515(11)
1.511(11)
1.417(8)
O-8
C-81 )0.0125(14)
O-81
C-9
O-9
0.2493(9)
0.1472(12)
0.2375(6)
0.2090(14)
0.0347(10)
0.3534(13)
0.2507(6)
0.4617(18)
0.495(2)
C-91
O-91
C-10
O-10
O-11
O-11
C-12
N-1
1.433(7)
1.442(7)
0.671(2)
with pyridine at 70 °C for 3 days, after O-Ac produced
N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-b- -glucopyrano-
side-6-yl)pyridinium tosylate (4b) in 62.5% yield; mp
0.3078(15)
0.3078(8)
0.3098(11)
0.1565(9)
0.4252(11)
0.7876(12)
0.7431(8)
0.6358(10)
0.8162(11)
0.8601(10)
D
C-21
C-22
C-23
20
163 °C; ½aŠ )15.13 (c 0.37, H2O). The reaction of 2b
D
with pyridine first at rt for 6 weeks, then 3 days at 70 °C
and after O-Ac, gave the same product in 73.5% yield.
Converting of 2a to the appropriate N-(methyl 2,3,4-tri-
aUeq is defined as one-third of the trace of the orthogonalized Uij
tensor.
O-acetyl-6-deoxy-a-
D-glucopyranoside-6-yl)-2-methyl-
20
D
negatively charged O-atoms from the tosylate anion.
These interactions are relatively strong with donor–
ꢁ
acceptor distances of about 3.3 A. Other interactions are
weaker and probably play a less important role.
pyridinium tosylate (5a) was successful in 48% yield; ½aŠ
52.38 (c 0.21, H2O) after 11 days at 70 °C and after O-Ac.
N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-b- -glucopyrano-
side-6-yl)-2-methylpyridinium tosylate (5b) was pro-
D
The reaction of compound 2 with triethylamine did
not give the expected quaternary ammonium salt. Evi-
dently, the tertiary aliphatic amine with ethyl substitu-
ents enlarges the steric hindrance so much that the
expected salts cannot be formed even in trace amounts.
Secondly, we tried to synthesize quaternary ammo-
nium salts with aromatic amines. The reactions of the a
duced in reaction of 2b with the 2-methylpyridine at rt for
6 weeks, first, and next at 70 °C for 16 days and after O-
20
Ac; ½aŠ )22.55 (c 0.51, H2O). The yields of these syn-
D
theses were higher for the b anomer than for methyl a-D-
glucopyranoside. In that case we also tested a number of
reaction conditions, but the best results we obtained were
at higher temperature (70 °C) and when the reaction
mixture was kept in a screw-capped ampoule.
and b anomer of methyl 6-O-tosyl-D-glucopyranoside
1
with pyridine and 2-methylpyridine gave four new qua-
ternary ammonium salts (4a and 4b, 5a and 5b, Scheme
1). Reaction of 2a with pyridine at rt (6 days) and after
that at 70 °C for next 6 days gave N-(methyl 2,3,4-tri-O-
Apart for the sugar-proton signals in the H NMR
spectra (compounds 4a, 4b, 5a and 5b, Tab le 1) proton
signals also exist that correspond to the pyridinium (Py)
ring (4a and 4b) or the 2-methylpyridinium ring (5a and
5b). The coupling constants J3;4 ¼ꢀ 9:0 Hz and
acetyl-6-deoxy-a-D-glucopyranoside-6-yl)pyridinium
20
D
1
tosylate (4a) in 35% yield; ½aŠ 11.74 (c 0.23, H2O).
J4;5 ¼ꢀ 9:0 Hz taken from their H NMR spectra verify
Methyl 6-O-tosyl-b-
D
-glucopyranoside (2b) in reaction
the 4C1 conformation of compounds 4a, 4b, 5a and 5b. The

L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
1541
Table 5. Selected torsion angles (°) for N-(methyl 2,3,4-tri-O-acetyl-6-
deoxy-b- -glucopyranoside-6-yl)trimethylammonium tosylate
D
Torsion angles
C-5–O-1–C-1–O-7
C-5–O-1–C-1–C-2
O-7–C-1–C-2–O-8
O-1–C-1–C-2–O-8
O-7–C-1–C-2–C-3
O-1–C-1–C-2–C-3
O-8–C-2–C-3–O-9
C-1–C-2–C-3–O-9
O-8–C-2–C-3–C-4
C-1–C-2–C-3–C-4
O-9–C-3–C-4–O-10
C-2–C-3–C-4–O-10
O-9–C-3–C-4–C-5
C-2–C-3–C-4–C-5
C-1–O-1–C-5–C-6
C-1–O-1–C-5–C-4
O-10–C-4–C-5–O-1
C-3–C-4–C-5–O-1
O-10–C-4–C-5–C-6
C-3–C-4–C-5–C-6
O-1–C-5–C-6–N-1
C-4–C-5–C-6–N-1
O-1–C-1–O-7–C-7
C-2–C-1–O-7–C-7
O-81–C-8–O-8–C-2
C-81–C-8–O-8–C-2
C-3–C-2–O-8–C-8
C-1–C-2–O-8–C-8
O-91–C-9–O-9–C-3
C-91–C-9–O-9–C-3
C-2–C-3–O-9–C-9
C-4–C-3–O-9–C-9
O-11–C-10–O-10–C-4
O-11–C-10–O-10–C-4
C-12–C-10–O-10–C-4
C-3–C-4–O-10–C-10
C-5–C-4–O-10–C-10
C-5–C-6–N-1–C-22
C-5–C-6–N-1–C-23
C-5–C-6–N-1–C-21
O-22–S-1–C-54–C-55
O-20–S-1–C-54–C-55
O-21–S-1–C-54–C-55
O-22–S-1–C-54–C-53
O-20–S-1–C-54–C-53
O-21–S-1–C-54–C-53
177.9(7)
)63.8(9)
)69.7(9)
173.0(6)
171.8(7)
54.5(9)
70.0(8)
)171.6(7)
)169.5(6)
)51.1(10)
)70.0(8)
172.7(6)
169.3(6)
51.9(9)
)174.2(6)
66.4(9)
)176.9(6)
)58.1(8)
65.3(9)
)175.9(7)
73.5(9)
Figure 1. The X-ray structure of N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-
b-D-glucopyranoside-6-yl)trimethylammonium tosylate.
)168.7(7)
)72.5(12)
170.3(11)
)3.0(15)
179.6(7)
)124.7(9)
114.0(9)
)11.4(15)
169.3(8)
)123.2(8)
115.8(8)
)24.4(17)
34.8(19)
)177.8(9)
113.7(10)
)126.6(10)
60.5(9)
on Kieselgel 60 F254 Silica Gel plates (E. Merck,
0.20 mm thickness). The spots were detected by spraying
with 5% ethanolic H2SO4 and charring. A Mercury-
400BB (400 MHz) spectrometer with D2O as a solvent
and acetone as an external standard, and 2D COSY,
HSQC technique at temperature of 25 °C was used.
3.2. X-Ray crystallography
X-Ray measurements were carried out on a KUMA
KM-4 four circle diffractometer. The structures were
solved by direct methods with the SHELXS program23
and refined employing full-matrix least-squares method
implemented in the SHELXL program.24 Anisotropic
displacement coefficients were applied to all non-
hydrogen atoms. The atomic scattering factors were
taken from the International Tables for X-ray Crystal-
lography (1993). Molecular illustrations were drawn
using the ORTEP program.25 Optical rotations were
measured with a JASCO J-20 polarimeter. Elemental
analyses were made with a Carlo Erba apparatus.
Positive-ion mode MALDITOF mass spectra were
obtained using a Bruker Biflex III spectrometer with
a-cyano-4-hydroxycinnamic matrix.
179.5(7)
)61.6(9)
)8.8(11)
)128.3(9)
112.9(9)
170.7(13)
51.2(13)
)67.6(13)
sequence of the proton positions for compounds 4a and 5a
are the same (H-2, H-3, H-4, H-1, H-6a, H-6b, H-5), and
the sequence of proton positions for compounds 4b and 5b
are similar (H-3, H-4, H-2, H-6a, H-6b, H-1, H-5).
3. Experimental
3.3. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-a-D-glucopyr-
anoside-6-yl)trimethylammonium tosylate (3a)
3.1. General methods
Methyl 6-O-p-toluenesulfonyl-a-D-glucopyranoside (2a)
Commercial methyl a-
b- -glucopyranoside (Fluka) were used. All reactions
were monitored by thin-layer chromatography (TLC)
D
-glucopyranoside and methyl
(40.4 mg, 0.117 mmol) was dissolved in 33% ethanolic
solution of Me3N (0.2 mL). The reaction mixture was
kept under ultrasonic conditions at rt. After 20 h under
D

1542
L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
Figure 2. Packing of N-(methyl 2,3,4-tri-O-acetyl-6-deoxy-b-
D
-glucopyranoside-6-yl)trimethylammonium tosylate with C–HÁ Á ÁO hydrogen bonds.
these conditions and 8 days at rt, the solvent was evapo-
rated to dryness under reduced pressure, and the crude
product was dissolved in pyridine (2.5 mL) and Ac2O
(2.5 mL) was added. Next, the solution was evaporated to
dryness. The residue was dissolved in H2O (10 mL),
washed three times with CHCl3. The aqueous layer was
evaporated and dried over P2O5 to give an oil of N-(me-
dissolved in H2O extracted with CHCl3. The aqueous
layer was evaporated and the residue was dried over
P2O5 to give the title compound as an oil (16.7 mg, 35%);
20
1
½aŠ 11.74 (c 0.23, H2O); H NMR (D2O): d 8.92–8.13
D
(m, 5H, Py), d 7.72–7.38 (2d, each 2H, Ph), 5.45 (t, 1H,
H-2, J2;3 9.6 Hz), 5.11 (m, 1H, H-3), 5.08 (t, br, 1H, H-4),
5.04 (d, 1H, H-1, J1;2 3.6 Hz), 4.98 (dd, 1H, H-6a, J6a;6b
11.6 Hz), 4.81 (dd, 1H, H-6b), 4.43 (ddd, 1H, H-5, J5;6a
3.0 Hz, J5;6b 7.2 Hz), 3.03 (s, 3H, –OCH3), 2.42 (s, 3H,
PhCH3), 2.21–2.10 (9H, 3 · OAc); 13C NMR (H2O): d
173.39–172.98 (2C, 2 · OOCCH3), 147.04–125.60 (6C,
Ph), 96.49 (C-1), 70.68 (C-2), 70.24 (C-3), 69.80 (C-4),
67.67 (C-5), 61.08 (C-6), 55.08 (OCH3), 20.69 (PhCH3),
20.39–20.18 (3C, COOCH3); Rf ¼ 0 (3:1 CHCl3–
MeOH). Anal. Calcd for C25H31NO11S (553.585): C,
54.24; H, 5.65; N, 2.53; S, 5.79; O, 31.78. Found: C,
54.05; H, 5.80; N, 2.75; S, 5.85. MALDITOF-MS
(CCA): m=z 382.1 ([M)OTs]þ).
thyl 2,3,4-tri-O-acetyl-6-deoxy-a-
yl)trimethylammonium tosylate (20.1 mg, 42%); ½aŠ
D-glucopyranoside-6-
20
D
92.46 (c 0.3, H2O); 1H NMR (D2O): d 7.73–7.39 (2d, each
2H, Ph), 5.45 (t, 1H, H-2, J2;3 9.6 Hz), 5.13 (d, 1H, H-1,
J1;2 3.6 Hz), 5.09 (t, br, 1H, H-3), 5.04 (t, 1H, H-4, J4;5
9.8 Hz), 4.62 (t, 1H, H-5, J5;6a 9.4 Hz), 3.73 (dd, 1H, H-6a,
J6a;6b 8.4 Hz), 3.57 (s, 3H, –OCH3), 3.48 (dd, 1H, H-6b),
3.25 (s, 9H, 3 · CH3 of N(CH3)3), 2.42 (s, 3H, PhCH3),
2.14–2.09 (9H, 3 · OAc); 13C NMR (H2O): d 173.34–
172.69 (3C, 3 · OOCCH3), 142.67–139.82 (2C, Ph),
129.67–125.63 (2C, Ph), 97.32 (C-1), 70.4 (C-2), 69.91 (C-
3), 69.88 (C-4), 66.35 (C-6), 64.70 (C-5), 57.82 (–OCH3),
54.51 (9C, N(CH3)3), 20.71 (PhCH3), 20.34–20.20 (3C,
COOCH3); Rf ¼ 0 (3:1 CHCl3–MeOH). Anal. Calcd for
C23H35NO11S (533.595): C, 51.77; H, 6.61; N, 2.63; S,
6.01; O, 32.98. Found: C, 51.82; H, 6.65; N, 2.70; S, 6.05.
MALDITOF-MS (CCA): m=z 362.2 ([M)OTs]þ).
3.5. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-a-D-glucopyr-
anoside-6-yl)-2-methylpyridinium tosylate (5a)
Methyl
6-O-p-toluenesulfonyl-a-D-glucopyranoside
(115.6 mg, 0.330 mmol) was dissolved in dry 2-methyl-
pyridine (1.08 mL). That solution was kept in a screw-
capped ampoule at 70 °C. After 11 days the solvent was
evaporated. That oil was dissolved in the mixture of
pyridine (6 mL) and Ac2O (6 mL). After 24 h, at rt the
solvent were evaporated. The residue was dissolved in
H2O and extracted with CHCl3. The aqueous layer was
3.4. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-a-D-glucopyr-
anoside-6-yl)pyridinium tosylate (4a)
Methyl
6-O-p-toluenesulfonyl-a-D-glucopyranoside
(95.7 mg, 0.275 mmol) was dissolved in dry pyridine
(2.2 mL), and phenol (catalytic amount) was added to
the reaction mixture. That solution was kept in a screw-
capped ampoule at rt for 6 days and at 70 °C for the next
6 days. After 12 days the solvent was evaporated, and
the residue was dissolved in pyridine (5 mL) and Ac2O
(5 mL) was added. Next, the solution was evaporated,
evaporated, and the residue was dried over P2O5 to give
20
the title compound as an oil (90.8 mg, 48%); ½aŠ 52.38
D
(c 0.21, H2O); 1H NMR (D2O): d 8.81–7.92 (m, 4H, Py),
d 7.72–7.38 (2d, each 2H, Ph), 5.44 (t, 1H, H-2, J2;3
9.8 Hz), 5.24 (t, 1H, H-3, J3;4 9.6 Hz), 5.16 (t, 1H, H-4,
J4;5 10.2 Hz), 5.01 (d, 1H, H-1, J1;2 3.6 Hz), 4.89 (dd, 1H,

L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
1543
H-6a, J6a;6b 11.6 Hz), 4.78 (dd, 1H, H-6b), 4.36 (ddd, 1H,
H-5, J5;6a 2.4 Hz, J5;6b 7.6 Hz), 2.92 (s, 3H, –OCH3), 2.91
(s, 3H, PhCH3-picoline), 2.42 (s, 3H, PhCH3), 2.21–2.09
(9H, 3 · OAc); 13C NMR (H2O): d 173.40–172.72 (3C,
3 · OOCCH3), 146.48–125.60 (9C, Ph), 96.37 (C-1),
70.74 (C-2), 70.31 (C-3), 70.22 (C-4), 68.06 (C-5), 57.15
(C-6), 54.91 (–OCH3), 20.69 (PhCH3), 20.34–20.19 (3C,
COOCH3), 17.03 (PhCH3); Rf ¼ 0 (3:1 CHCl3–MeOH).
Anal. Calcd for C26H33NO11S (567.612): C, 55.02; H,
5.86; N, 2.47; S, 5.65; O, 31.00. Found: C, 55.54; H,
5.82; N, 2.72; S, 5.71. MALDITOF-MS (CCA): m=z
396.1 ([M)OTs]þ).
concentrated to an oil. The oil crystallized from AcOEt
to give the title compound; (72.4 mg, 62.5%); mp 163 °C,
20
D
1
½aŠ )15.13 (c 0.37, H2O); H NMR (D2O): d 8.89–8.13
(m, 5H, Py), 7.72–7.38 (2d, each 2H, Ph), 5.38 (t, 1H, H-
3, J3;4 9.6 Hz), 5.11 (t, 1H, H-4, J4;5 9.6 Hz), 5.02 (m, 1H,
H-2), 4.98 (dd, br, 1H, H-6a), 4.79 (dd, 1H, H-6b), 4.61
(d, 1H, H-1, J1;2 8.0 Hz), 4.29 (ddd, 1H, H-5, J5;6a 2.8 Hz,
J5;6b 6.6 Hz), 3.32 (s, 3H, –OCH3), 2.42 (s, 3H, PhCH3),
2.21–2.02 (9H, 3 · OAc); 13C NMR (H2O): d 173.27–
172.89 (3C, 3 · OOCCH3), 147.06–125.61 (6C, Ph),
100.86 (C-1), 73.05 (C-3), 71.38 (C-5), 71.36 (C-2), 69.97
(C-4), 61.17 (C-6), 57.20 (OCH3), 20.70 (PhCH3), 20.38–
20.24 (3C, COOCH3); Rf ¼ 0 (3:1 CHCl3–MeOH).
Anal. Calcd for C25H31NO11S (553.585): C, 54.24; H,
5.65; N, 2.53; S, 5.79; O, 31.78. Found: C, 54.03; H,
5.84; N, 2.95; S, 5.90. MALDITOF-MS (CCA): m=z
382.1 ([M)OTs]þ).
3.6. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-b-D-glucopyr-
anoside-6-yl)trimethylammonium tosylate (3b)
Solution of trimethylamine (33%) in EtOH (2.3 mL) was
added to methyl 6-O-p-toluenesulfonyl-b- -glucopyr-
D
anoside (104.2 mg, 0.300 mmol). The reaction mixture
was kept in a screw-capped ampoule under ultrasonic
conditions at rt for 20 h and then for 8 days at rt. The
reaction mixture was evaporated to the dryness. The oily
residue was dissolved in a mixture of pyridine (6.5 mL)
and Ac2O (6.5 mL). N-(Methyl 2,3,4-tri-O-acetyl-6-
3.8. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-b-D-glucopyr-
anoside-6-yl)-2-methylpyridinium tosylate (5b)
Methyl 6-O-p-toluenesulfonyl b-D-glucopyranoside
(68.6 mg, 0.200 mmol) was dissolved in dry 2-methyl-
pyridine (0.64 mL). The solution was kept in a screw-
capped ampoule: first at rt for 6 weeks, next at 70 °C for
16 days. After that time the solvent was evaporated. The
oil was dissolved in pyridine (3 mL) and Ac2O (3 mL)
was added. After 24 h the solution was evaporated. The
residue was dissolved in H2O and extracted with CHCl3.
deoxy-b-D-glucopyranoside-6-yl)trimethylammonium
tosylate crystallized from the solution of pyridine and
20
Ac2O (52.6 mg, 33%); mp 210–220 °C; ½aŠ )2.28 (c
D
0.175, H2O); 1H NMR (D2O): d 7.64–7.30 (2d, each 2H,
Ph), 5.28 (t, 1H, H-2, J2;3 9.4 Hz), 4.95 (t, 1H, H-3, J3;4
9.2 Hz), 4.93 (t, 1H, H-4, J4;5 8 Hz), 4.77 (d, 1H, H-1, J1;2
8 Hz), 4.39 (t, 1H, H-5, J5;6a 9.2 Hz;), 3.62 (dd, 1H, H-6a,
J6a;6b 10 Hz), 3.47 (s, 3H, –OCH3), 3.44 (dd, 1H, H-6b),
3.17 (s, 9H, N(CH3)3), 2.33 (s, 3H, PhCH3), 2.05–1.99
(9H, 3 · OAc); 13C NMR (H2O): d 173.24–172.66 (3C,
3 · OOCCH3), 142.68–139.77 (2C, Ph), 129.68–125.62
(2C, Ph), 100.69 (C-1), 73.08 (C-2), 71.06 (C-4), 69.66
(C-3), 68.20 (C-5), 66.12 (C-6), 57.68 (OCH3), 54.46 (9C,
N(CH3)3), 20.70 (PhCH3), 20.32–20.23 (3C, COOCH3);
Rf ¼ 0 (3:1 CHCl3–MeOH). Anal. Calcd for
C23H35NO11S (533.595): C, 51.77; H, 6.61; N, 2.63; S,
6.01; O, 32.98. Found: C, 51.65; H, 6.64; N, 2.69; S,
6.11. MALDITOF-MS (CCA): m=z 362.2 ([M)OTs]þ).
The aqueous layer was evaporated and dried over P2O5
20
D
to give title compound (64.6 mg, 58%); ½aŠ )22.55 (c
1
0.51, H2O); H NMR (D2O): d 8.76–7.91 (m, 4H, Py),
7.71–7.37 (2d, each 2H, Ph), 5.37 (t, 1H, H-3, J3;4
9.6 Hz), 5.23 (t, 1H, H-4, J4;5 9.6 Hz), 5.03 (q, 1H, H-2,
J2;3 8.4 Hz), 4.91 (dd, 1H, H-6a, J6a;6b 12.4 Hz), 4.76 (dd,
1H, H-6b), 4.55 (d, 1H, H-1, J1;2 8.4 Hz), 4.28 (ddd, 1H,
H-5, J5;6a 2.4 Hz, J5;6b 7.6. Hz), 3.28 (s, 3H, –OCH3), 2.90
(s, 3H, CH3-picoline), 2.41 (s, 3H, PhCH3), 2.21–2.10
(9H, 3 · OAc); 13C NMR (H2O): d 173.29–172.84 (3C,
3 · OOCCH3), 156.36–125.60 (9C, Ph), 100.73 (C-1),
73.13 (C-3), 71.38 (C-5), 71.32 (C-2), 70.39 (C-4), 57.47
(C-6), 57.10 (OCH3), 20.66 (PhCH3), 20.33–20.27 (3C,
COOCH3), 20.06 (1C, CH3-picoline); Rf ¼ 0 (3:1
CHCl3–MeOH). Anal. Calcd for C25H31NO11S
(553.585): C, 54.24; H, 5.65; N, 2.53; S, 5.79; O, 31.78.
Found: C, 54.34; H, 5.57; N, 2.49; S, 5.83. MALDI-
TOF-MS (CCA): m=z 396.1 ([M)OTs]þ).
3.7. N-(Methyl 2,3,4-tri-O-acetyl-6-deoxy-b-D-glucopyr-
anoside-6-yl)pyridinium tosylate (4b)
Methyl
6-O-p-toluenesulfonyl-b-D-glucopyranoside
(72.8 mg, 0.210 mmol) and a catalytic amount of phenol
were placed in a screw-capped ampoule. The reactant
and catalyst were dissolved in dry pyridine (0.55 mL).
The solution was kept in a screw-capped ampoule and
heated at 70 °C for 3 days. After that time the solution
was evaporated to dryness, and the residue was dis-
solved in a mixture of pyridine (3 mL) and Ac2O (3 mL).
After 24 h the solution was evaporated to dryness. The
residue was dissolved in H2O, extracted with CHCl3 and
4. Supplementary material
Full crystallographic details, excluding structure factors,
have been deposited (deposition no. CCDC 222217)
with the Cambridge Crystallographic Data Centre.
These data may be obtained, on request, from the

1544
L. Pellowska-Januszek et al. / Carbohydrate Research 339 (2004) 1537–1544
9. Lemieux, R. U.; Morgan, A. R. Can. J. Chem. 1965, 43,
2205–2213.
10. Sinnott, M. L.; Withers, S. G. Biochem. J. 1974, 143, 751–
762.
CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK.
Tel.: +44 1223 336408, fax: +44 1223 336033, e-mail:
deposit@ccdc.cam.ac.uk.
11. Jones, C. C.; Sinnot, M. L.; Soouchard, J. L. J. Chem.
Soc., Perkin Trans. 2 1977, 1191–1199.
12. Withers, S. G.; Jullien, M.; Sinnott, M. L.; Yon, J. M. Eur.
J. Biochem. 1978, 87, 249–256.
Acknowledgements
13. Legler, G.; Sinnott, M. L. J. Chem. Soc., Perkin Trans. 2
1980, 1377–1383.
14. Lemieux, R. U.; Lown, J. W. Can. J. Chem. 1963, 41, 889–
897.
€ ꢀ
15. Paulsen, H.; Gyorgydeak, Z.; Friedman, M. Chem. Ber.
1974, 107, 1590–1613.
This work was partially financed by grant BW/8000-5-
0223-3 and DS/8361-4-0134-3. We thank M.Sc. Leszek
Łobocki for measurements of mass spectra (MALDI-
TOF).
16. Finch, P.; Nagpurkar, A. G. Carbohydr. Res. 1976, 49,
275–287.
17. Abel, T.; Cohen, J. I.; Engel, R.; Filshtinskaya, M.;
Melkonian, A.; Melkonian, K. Carbohydr. Res. 2002, 337,
2495–2499.
18. Dmochowska, B.; Bednarczyk, D.; Nowacki, A.; Konitz,
ꢀ
A.; Wojnowski, W.; Wisniewski, A. Carbohydr. Res. 2000,
329, 703–707.
19. Dmochowska, B.; Nowacki, A.; Wojnowski, W.; Konitz,
References
1. Jones, G. Pyridines and their Benzo Derivatives. In
Comprehensive Heterocyclic Chemistry; Katrizky, A. R.,
Rees, Ch., Eds.; Pergamon: Oxford, 1984; Vol. 2, Part 2A, pp
395–510.
ꢀ
2. Sliwa, W. N-Substituted Salts of Pyridine and Related
Compounds; WSP: Czestochowa, Poland, 1996; pp 3–427;
and references cited therein.
ꢀ
A.; Wisniewski, A. Carbohydr. Res. 2001, 330, 431–435.
20. Skorupowa, E.; Kurszewska, M.; Konitz, A.; Wojnowski,
z
3. Menschutkin, N. Z. Phys. Chem. 1890, 5, 589–600.
4. Fischer, E.; Raske, K. Ber. Dtsch. Chem. Ges. 1910, 43,
1750–1753.
ꢀ
W.; Wisniewski, A. Carbohydr. Res. 2001, 331, 343–346.
21. Konitz, A.; Dmochowska, B.; Nowacki, A.; Wojnowski,
ꢀ
W.; Wisniewski, A. Carbohydr. Res. 2001, 333, 257–261.
5. Karrer, P.; Smirnoff, A. P. Helv. Chim. Acta 1921, 4, 817–
820.
22. Sairam, P.; Puranik, R.; Rao, B. S.; Swamy, P. V.;
Chandra, S. Carbohydr. Res. 2003, 338, 303–306.
23. SHELXS. Sheldrick, G. M. Acta Crystallogr. 1990, A46,
467–473.
24. Sheldrick, G. M. SHELXL. Program for the Refinement of
€
Crystal Structures, University of Gottingen, Germany,
€
6. Karrer, P.; Ringier, B. H.; Buchi, J.; Fritzche, H.;
Sollmssen, U. Helv. Chim. Acta 1937, 20, 55–71.
7. Lemieux, R. U.; Morgan, A. R. J. Am. Chem. Soc. 1963,
85, 1889–1890.
8. Lemieux, R. U.; Morgan, A. R. Can. J. Chem. 1965, 43,
2214–2221.
1997.
25. ORTEP-3. Farrugia, L. J. Appl. Crystallogr. 1997, 30, 565.