Crystal structures of O-acetylated 2-acylamino-2-deoxy-D-galactose derivatives

Article abstract of DOI:10.1016/S0008-6215(03)00352-5

The X-ray structures of 1,3,4,6-tetra-O-acetyl-2-deoxy-α -D-galactopyranoside derivatives with four different 2-(acylamino) substituents have been determined with Mo K_α radiation at 123 K. The structure of the 2-acetylamino derivative and of its acyl-homologs with a 2-(propanoylamino)-, 2-(butanoylamino)-, and 2-(2-methyl-propanoylamino)-group crystallized in the monoclinic space group C2. The pyranose unit of all compounds has the usual ⁴C₁ shape. The different orientations of the 6-O-acetyl-groups are discussed. Conformations of the acylamino-group are compared to those found in the crystal structure of N-acetyl-α-D-galactosamine.

Full text of DOI:10.1016/S0008-6215(03)00352-5

Carbohydrate Research 338 (2003) 2119ꢀ2128
/
www.elsevier.com/locate/carres
Crystal structures of O-acetylated 2-acylamino-2-deoxy-
derivatives
D-galactose
a
Thomas Mikeska, Martin Nieger, Heidi Mansikkam a¨ ki, J o¨ rg Daniels,
b
c
b
a,
Thomas Kolter *
a
Kekul e´ -Institut f ¨u r Organische Chemie und Biochemie der Universit ¨a t, Gerhard-Domagk-Str.1, D-53121 Bonn, Germany
b
Institut f ¨u r Anorganische Chemie der Universit ¨a t, Gerhard-Domagk-Str.1, D-53121 Bonn, Germany
c
Department of Chemistry, University of Jyv ¨a skyl ¨a , P.O. Box 35, FIN-40351 Jyv ¨a skyl ¨a , Finland
Received 22 April 2003; received in revised form 17 July 2003; accepted 20 July 2003
Abstract
The X-ray structures of 1,3,4,6-tetra-O-acetyl-2-deoxy-a-
D-galactopyranoside derivatives with four different 2-(acylamino)
substituents have been determined with Mo K radiation at 123 K. The structure of the 2-acetylamino derivative and of its acyl-
a
homologs with a 2-(propanoylamino)-, 2-(butanoylamino)-, and 2-(2-methyl-propanoylamino)-group crystallized in the monoclinic
4
space group C2. The pyranose unit of all compounds has the usual C
1
shape. The different orientations of the 6-O-acetyl-groups
D-
are discussed. Conformations of the acylamino-group are compared to those found in the crystal structure of N-acetyl-a-
galactosamine.
#
2003 Elsevier Ltd. All rights reserved.
Keywords: Amino sugars; 2-(Acylamino)-2-deoxy-D-galactose; X-ray structures
5
1992 using N-acyl-modified D-mannosamine deriva-
1. Introduction
tives like N-propanoyl- and N-butanoyl-D-mannosa-
mine.
N-Acetyl-D-galactosamine is a naturally occurring
building block of glycoproteins, glycolipids, and glyco-
We have been especially interested in analogs of N-
acetyl- -galactosamine (GalNAc). This amino sugar is
biosynthetically incorporated into glycosphingolipids of
1
saminoglycans implicated in cell recognition events.
D
Cell surfaces can be modified by the exogenous addition
2
,3
4
6,7
of carbohydrate- and lipid analogs to cells, followed
by their metabolic incorporation into components of the
plasma membrane. Such cell surface engineering can
lead to functional alteration of cellular properties, like
the ganglio-series by a b-N-acetyl-
D
-galactosaminyl-
transferase. Here, we report on the preparation and
structural characterization of a series of N-acyl
galacto configured sugar analogs. Per-O-acetylated N-
acetyl-a- -galactosamine (9) and the acyl-homologs
target molecules 10ꢀ12 are easily accessible, as indicated
8
,9
D-
2
ꢀ4
D
virus binding, or membrane receptor function.
The
/
metabolic transformation of amino sugar analogs into
non-natural sialic acids and their subsequent incorpora-
tion into glycoconjugates has been demonstrated in
in Fig. 1. They have been prepared as potential cell
permeable prodrugs, which might intracellularly gener-
ate the free sugar analogs after enzymatic ester
1
0ꢀ12
cleavage.
The structures of the 2-acetylamino
derivative 9 and of its acyl-homologs with a 2-(propa-
noylamino)- (10), 2-(butanoylamino)- (11), and 2-(2-
methyl-propanoylamino)-group (12) are discussed.
*
Corresponding author. Tel.: ꢁ
28-737778.
E-mail address: tkolter@uni-bonn.de (T. Kolter).
/
49-228-735798; fax: ꢁ49-
/
2
0008-6215/03/$ - see front matter # 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0008-6215(03)00352-5

2120
T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ2128
/
be described by the endocyclic torsion angles (Table 2).
The range of the ring torsion angles, 52.8(2)ꢀ58.9(2)8,
show only a slight deviation from 608 of an ideal chair
conformation as in cyclohexane, and of 55.8ꢀ61.78 as in
an ideal pyranose ring. These values are in agreement
/
/
1
8
1
6
with the torsion angles of 54.9(3)ꢀ
/
59.0(3)8
and
-galactosa-
1
7
5
5.8(5)ꢀ
/
60.2(5)8
found in N-acetyl-a-
D
mine.
The acetylamino-group in N-acetyl-a-
D
-galactosa-
mine is in a Z-anti conformation. This Z-anti conforma-
tion is also found in the acylamino-groups of the title
compounds as indicated by the torsion angles C2Ã
C21ÃC22 with values in the range of 164.5(2)ꢀ179.5(4)8
Table 2; ideal: 91808 for anti conformation). In N-
acetyl-a- -galactosamine, this torsion angle is
/
N21Ã
/
/
/
(
/
D
1
7
1
79.0(5)8. The torsion angle C2Ã
ranging from 1.8(8) to ꢂ11.8(7)8 show in part consider-
able deviation from planarity of the acylamino-group
Table 2; ideal: 908 for planar arrangement). In
contrast to these values in the title compounds, the
acetylamino-group in -galactosamine
N-acetyl-a-
shows nearly ideal planarity as indicated by the torsion
/
N21Ã
/
C21Ã
/
O21(2)
/
(
/
D
1
7
Fig. 1. Synthesis scheme for compounds 9ꢀ/12. DMAP, 4-
angle of ꢂ0.4(8)8. Further bond lengths and angles of
/
dimethylaminopyridine.
the acylamino-groups are given in Table 2.
The O-acetyl-groups in the target compounds are in a
cisoid-planar conformation. This is in agreement with
19
those found in other O-acetylated pyranoses. The
cisoid-planar conformation is characterized by the
2
. Results and discussion
2
.1. Synthesis
torsion angles Ci Ã
Oi1ÃCi1ÃOi2 (iꢃ
angles are in the range from ꢂ
(ideal: 91808 for cisoid conformation), and the second
torsion angles from ꢂ0.2(3) to 8.2(8)8 (ideal: 908 for
/
Oi1Ã
3, 4, 6) (Table 2). The first torsion
173.6(4) to 180.0(2)8
/
Ci1Ã
/
Ci2 (iꢃ
/
3, 4, 6) and Ci Ã
/
/
/
/
The following target compounds were prepared accord-
ing to modified procedures described in the litera-
/
/
1
3,14
ture
amino)-2-deoxy-a-
tetra-O-acetyl-2-deoxy-2-(propanoyl-amino)-a-
topyranoside (10), 1,3,4,6-tetra-O-acetyl-2-(butanoyla-
mino)-2-deoxy-a- -galactopyranoside (11), and 1,3,4,6-
tetra-O-acetyl-2-deoxy-2-(2-methyl-propanoylamino)-
a- -galactopyranoside (12). The starting material for
compounds 10ꢀ12 was -galactosamine-hydrochloride
1), and N-acetyl- -galactosamine (2) for compound 9.
The amino function of 1 was converted to an acylamino
group with the appropriate acid anhydrides 3ꢀ5,
(Fig. 1): 1,3,4,6-tetra-O-acetyl-2-(acetyl-
-galactopyranoside (9), 1,3,4,6-
-galac-
/
/
D
cisoid conformation). Only the 3-O-acetyl-group and
the 4-O-acetyl-group in 9 show a small deviation from
planarity. This deviation has no influence on the cisoid-
planar arrangement of the carbon-atom of the ring and
the oxygen-atom of the carbonyl group. The preferred
cis over the trans conformation is apparently a result of
D
D
D
2
0
/
D
electronic effects.
(
D
The orientations of the 6-O-acetyl-groups relative to
the pyranose ring are different in the four title com-
pounds. For compound 9, this group is found in a
/
respectively. The free hydroxyl groups were protected
with acetyl groups resulting in an anomeric mixture of
the title compounds. Recrystallization from ethyl ace-
transꢀ
in a gaucheꢀ
conformation is characterized by the torsion angles O1Ã
C5ÃC6ÃO6 and C4ÃC5ÃC6ÃO6, respectively (Table
). A graphical presentation is given in Fig. 6. In the
ideal case, a torsion angle for a gauche conformation is
608, and 91808 for the trans conformation. In the
title compounds, the torsion angles for the gauche
conformation are in the range from 53.1(5) to 77.5(5)8,
and for the trans conformation in a range from 158.3(4)
to 174.4(4)8 (Table 2). In contrast to this observation, in
/
gauche (tg) arrangement, whereas in 10ꢀ
/
12, it is
/trans (gt) conformation. The respective
/
tate resulted in the pure a-configured compounds 9ꢀ
/12.
/
/
/
/
/
2
1
2
2
.2. Crystal structure determination
9
/
/
1
5
The structures of 9ꢀ
shown in Figs. 2ꢀ5. Selected geometrical parameters are
listed in Table 1. Like in N-acetyl-a- -galactosa-
the pyranose ring of the title compounds is
/12 with the atom numbering are
/
D
1
6,17
mine,
in the typical C conformation. This conformation can
4
the crystal structure of N-acetyl-a-
D-galactosamine, a
1

T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ
/
2128
2121
Fig. 2. The structure of 9, showing the atom-numbering scheme and displacement ellipsoids at the 50% probability level for non-H
15a
atoms. The asymmetric unit contains two molecules.
Fig. 4. The structure of 11, showing the atom-numbering
scheme and displacement ellipsoids at the 50% probability
1
5b
level for non-H atoms.
cyclic oxygen-atoms O-11 are in a gauche (ꢁ
tion. The values for this torsion angle are in the range
/
g) orienta-
Fig. 3. The structure of 10, showing the atom-numbering
scheme and displacement ellipsoids at the 50% probability
1
5a
level for non-H atoms.
from 59.6(2) to 63.1(4)8 (Table 3). The endocyclic C1Ã
/
O1 bond lengths are in the range from 1.39(1) to 1.42(1)
˚
A (Table 3) and are slightly shorter then the averaged
gaucheꢀ
/
gauche (gg) conformation of the torsion angles
1
6
˚
O bond lengths of 1.43(1) A.
24
O1ÃC5Ã
/
/
C6Ã
/
O6 and C4Ã
/
C5Ã
/
C6Ã
/
O6 is found.
CÃ
/
2
5
The bond lengths and angles around the anomeric
center (Table 3) are of special interest, because they are
strongly correlated to theories and models of the
The exo-anomeric effect describes the preferred
gauche orientation of the carbon-atom of the aglycon
(C-11) with respect to a rotation around the exocyclic
2
2,23
anomeric effect.
The (endo-) anomeric effect de-
bond (C1Ã
This arrangement is defined by the exo-anomeric
torsion angle O1ÃC1ÃO11ÃC11 (Table 3).
In the title compounds, the 1-O-acetyl groups show a
gauche (ꢁg) arrangement. Therefore, the aglycon is
/
O11) to the endocyclic oxygen-atom O-1.
scribes the preferred axial orientation of an electrone-
gative substituent at the anomeric center compared to
the equatorial position relative to cyclohexane.
/
/
/
In the title compounds, the 1-O-acetyl-groups are in
/
an axial position. The anomeric torsion angle C5Ã
/
O1Ã
/
oriented towards the direction of the endocyclic oxygen-
atom O-1. The conformation around the anomeric
C1ÃO11 between the carbon-atoms C-5 and the exo-
/

2122
T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ2128
/
carbon-atom can be described as a (ꢁ
/
g, ꢁg)-confor-
/
mation, or as an ax-exo-syn conformation, respec-
2
6
tively. The exocyclic C1Ã
/
O11 bond lengths (Table 3)
are in the range of the averaged CÃ
/O bond lengths of
2
4
˚
1
.43(1) A.
Tables 4ꢀ
codes of the hydrogen-bonding geometry in the crystals
of the title compounds. The compounds 10ꢀ12 show a
similar network of their hydrogen bonds. One inter-
molecular NÃHÁ Á ÁO hydrogen bond of normal
is present. The proton attached to the
/7 show geometric details and the symmetry
/
/
2
7
strength
nitrogen atom of the acylamino group of a given
molecule forms a hydrogen bond to the carbonyl group
oxygen of the acylamino group of another molecule.
Only compound 11 with a bond angle N21Ã
/
H21Ã/O21
of 1438 shows a slight deviation from the nearly linear
arrangement (ideal: 1808 for linear arrangement) in the
crystal (Table 6). Within such hydrogen bonds, the value
of this bond angle is most often found to be in the range
from 160 to 1708. Furthermore, this arrangement
spreads like a chain inside the crystal as illustrated for
Fig. 5. The structure of 12, showing the atom-numbering
scheme and displacements ellipsoids at the 50% probability
1
5a
level for non-H atoms.
2
7
compound 10 (Figs. 7 and 8). Additional five weak
Table 1
Crystal data and structure refinement
9
10
11
12
Empirical formula
Formula weight
Unit cell dimensions
C
389.35
16
H
23NO10
C
17
H
25NO10
C
18
H
27NO10
18
C H27NO10
403.38
417.41
417.41
˚
a (A)
35.2322(6)
9.2859(2)
12.4737(2)
107.062(2)
3901.32(12)
8
16.8743(3)
9.2640(3)
14.8649(4)
117.347(2)
2064.03(9)
4
17.1624(2)
9.3055(1)
15.1385(2)
119.3363(6)
2107.64(4)
4
16.8087(3)
9.4611(2)
15.1526(3)
118.772(1)
2112.20(7)
4
˚
b (A)
˚
c (A)
b (8)
3
˚
V (A )
Formula units Z
ꢂ3
D
Absorption coeffi-
calcd (mg m
)
1.326
0.111
1.298
0.108
1.315
0.108
1.313
0.108
ꢂ1
cient (mm
F(000)
)
1648
856
888
888
Crystal size (mm)
0.60ꢄ
1.71ꢀ25.00
415h 5
k 511, ꢂ145
Reflections collected/ 36,586/6876 [Rint
unique 0.0529]
/
0.40ꢄ
/
0.20
0.55ꢄ
2.72ꢀ25.00
205h 5
k 510, ꢂ175
9429/3641 [Rint
3641/2/261
1.026
/
0.35ꢄ
/
0.15
0.79ꢄ
2.95ꢀ24.99
205h 5
k 511, ꢂ185
/
0.28ꢄ
/
0.14
0.55ꢄ
2.76ꢀ27.48
215h 5
k 512, ꢂ195
10,044/4640 [Rint
0.0438]
4640/1/269
/
0.50ꢄ0.40
/
u range (8)
Limiting indices
/
/
/
/
ꢂ
/
/
/
41, ꢂ
/
115
/
ꢂ
/
/
/
19, ꢂ
/
105
/
ꢂ
/
/
/
20, ꢂ
/
115
/
ꢂ
/
/
/
21, ꢂ
/
125
/
/
/
/
l 5
/
14
/
/
/
l 5
/
17
/
/
/
l 5
/
18
/
/
/
l 5
/
19
ꢃ
/
ꢃ
/
0.0384] 30,215/1984 [Rint
0.0914]
1984/1/267
ꢃ
/
ꢃ
/
Data/restraints/para- 6876/3/503
meters
2
Goodness-of-fit on F 1.073
1.062
0.973
Final R indices [I ꢀ
/
R
0.1970
1
ꢃ
/
0.0718, wR
2
ꢃ
/
R
1
ꢃ
/
0.0406, wR
2
ꢃ
/
R
1
ꢃ
/
0.0288, wR
2
ꢃ
/
R
0.0788
1
ꢃ
/
0.0367, wR
2
ꢃ
/
2s(I)]
0.0967
0.0752
R indices (all data)
R ꢃ
/
0.0768, wR ꢃ
/
R ꢃ
/
0.0501, wR ꢃ
/
R ꢃ
/
0.0305, wR ꢃ
/
R ꢃ
/
0.0491, wR ꢃ
/
1
2
1
2
1
2
1
2
0
.2012
0.1003
0.0(10)
0.0768
0.0837
Flack-parameter
Largest difference
ꢂ
/0.3(15)
ꢂ0.1(9)
/
ꢂ0.1(7)
/
0.571/ꢂ0.442
/
0.359/ꢂ
/
0.264
0.191/ꢂ
/
0.212
0.227/ꢂ0.181
/
ꢂ3
˚
peak/hole (e A
)
All compounds crystallized in the monoclinic space group C2 (aꢃ
/
gꢃ908).
/

T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ
/
2128
2123
Table 2
˚
Selected geometric parameters (A, 8, estimated standard deviations in parentheses)
9
10
11
12
Endocyclic torsion angles
C1Ã
C2Ã
C3Ã
C4Ã
C5Ã
O1Ã
/
C2Ã
C3Ã
C4Ã
C5Ã
O1Ã
C1Ã
/
C3Ã
C4Ã
C5Ã
O1Ã
C1Ã
C2Ã
/
C4
C5
O1
ꢂ
/
54.5(5); ꢂ
53.4(4); 57.7(4)
54.6(5); ꢂ57.0(4)
58.5(5); 56.9(5)
57.6(5); ꢂ55.1(5)
/
56.0(4)
ꢂ
/
56.3(2)
55.0(2)
54.1(2)
56.9(2)
58.5(2)
57.3(2)
ꢂ
/
57.1(2)
54.9(2)
53.3(2)
56.8(2)
58.9(2)
ꢂ
/
57.6(2)
55.4(2)
52.8(2)
55.6(2)
58.0(2)
/
/
/
/
/
/
ꢂ
/
/
ꢂ
/
ꢂ
/
ꢂ
/
/
/
/
C1
C2
C3
/
/
/
ꢂ
/
/
ꢂ
/
ꢂ
/
ꢂ
/
/
/
/
55.1(5); 53.7(5)
58.3(2)
58.2(2)
Acylamino-group
N21ÃC21
C21Ã
C21Ã
/
1.350(6); 1.329(6)
1.228(6); 1.224(6)
1.498(7); 1.531(7)
1.334(3)
1.244(3)
1.503(4)
1.342(3)
1.233(3)
1.507(3)
1.347(2)
1.238(2)
1.511(2)
/O21(2)
/C22
C22Ã
/
C23
1.442(4)
1.530(3)
1.522(4)
1.518(2)
1.532(3)
C23Ã
/
C24
C2Ã
/
N21Ã
/
C21Ã
/
C22
179.5(4); 166.3(4)
ꢂ
3.5(4)
/
177.4(2)
175.1(2)
164.5(2)
C2Ã
/
N21Ã
/
C21Ã
/
O21(2)
1.8(8); ꢂ11.8(7)
/
ꢂ4.6(3)
/
ꢂ11.7(2)
/
N21Ã
C21ÃC22Ã
N21ÃC21Ã
/
C21Ã
C23Ã
C22Ã
/
C22Ã
C24
C24
/
C23
ꢂ
/
138.2(3)
ꢂ
55.3(2)
/
114.3(2)
148.7(2)
/
/
/
/
/
/
ꢂ88.4(2)
/
Planarity of the O-acetyl-groups
C3Ã
/
O31Ã
/
C31Ã
/
C32
O32
ꢂ
/
174.9(4); 174.3(4)
ꢂ
0.3(3)
/
177.2(2)
180.0(2)
ꢂ
1.4(3)
/
177.8(2)
C3Ã
/
O31Ã
/
C31Ã
/
8.2(8); ꢂ5.1(6)
/
ꢂ0.3(3)
/
C4Ã
/
O41Ã
/
C41Ã
/
C42
O42
ꢂ
/
175.2(4); 177.7(4)
ꢂ
/
179.2(2)
ꢂ
/
179.4(2)
179.2(2)
C4Ã
/
O41Ã
/
C41Ã
/
5.8(7); ꢂ1.8(6)
/
ꢂ0.2(3)
/
ꢂ0.2(3)
/
ꢂ0.7(2)
/
C6Ã
/
O61Ã
/
C61Ã
/
C62
O62
175.6(5); ꢂ173.6(4)
/
178.7(3)
1.9(4)
ꢂ
/
179.0(3)
ꢂ
0.7(3)
/
178.1(2)
C6Ã
/
O61Ã
/
C61Ã
/
ꢂ3.6(8); 1.9(8)
/
ꢂ
/
ꢂ0.4(4)
/
Conformation of the 6-O-acetyl-group
O1ÃC5ÃC6ÃO61
C4ÃC5ÃC6ÃO61
/
/
/
158.3(4); ꢂ
/
174.4(4)
70.4(2)
167.5(2)
72.1(2)
165.2(2)
73.7(2)
/
/
/
ꢂ77.5(5); ꢂ
/
/53.1(5)
ꢂ
/
ꢂ
/
ꢂ164.1(1)
/
Compound 9 contains two molecules in the asymmetric unit, whereas the second value is correlated with the (?) marked molecule
Fig. 2).
(
intermolecular hydrogen bonds are found in the crystals
Tables 5ꢀ7).
The reason for the nearly isomorphous crystal struc-
tures and the similar hydrogen bond pattern of com-
pounds 10ꢀ12 may be a result of the intermolecular NÃ
HÁ Á ÁO hydrogen bond formation. The development of
this pattern during the crystallization process seems to
occur regardless of the steric demands of the acylamino-
group.
The intermolecular hydrogen bond of normal strength
described above is also found in 9. However, there are
two molecules in the asymmetric unit, and the values
found for this bonding are slightly different (Table 4).
Nevertheless, they also show a nearly linear arrange-
ment as indicated by their bond angles of 164(5) and
(
/
/
/
169(5)8, respectively. These intermolecular hydrogen
bonds can also be described like a chain and are shown
in Figs. 9 and 10. Eight additional weak intermolecular
hydrogen bonds are found in the crystal (Table 4).
The structural data of the ring system and the
acylamino-groups constitute an improved basis for
molecular modeling approaches towards neoglycocon-
jugates containing these structures.
Fig. 6. Newman projection along the C5Ã
the transꢀgauche (tg) and the gaucheꢀtrans (gt) conforma-
tion. The (tg) conformation is found in 9, and the (gt)
conformation in 10ꢀ12.
/
C6 bond (arrow) in
/
/
/

2124
T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ2128
/
Table 3
Table 5
Hydrogen-bonding geometry (A, 8) for 10
˚
˚
Selected geometric parameters (A, 8) around the anomeric
center
D Ã
/
HÁ Á ÁA
d(D Ã
/
d(HÁ Á ÁA) d(DÁ Á ÁA) B
/
9
10
11
12
H)
(DHA)
C1Ã
O1Ã
C1Ã
C1Ã
O1Ã
/
O1
1.387(6);
1.404(3) 1.402(2) 1.399(2)
1.434(3) 1.442(2) 1.448(2)
1.443(3) 1.444(2) 1.440(2)
N21Ã
#1
C5Ã
C6Ã
C32Ã
#4
C62Ã
/
H21Á Á ÁO21
0.83(2) 2.03(2)
2.829(3) 165(3)
1
.421(5)
1.440(6);
.434(5)
1.432(6);
.427(5)
/
C5
/
H5Á Á ÁO62 #2
1.00
2.41
2.35
2.43
3.334(4) 153
3.291(3) 158
3.280(4) 144
1
/
H6AÁ Á ÁO42 #3 0.99
/O11
/
H32AÁ Á ÁO1
0.98
1
/
H62AÁ Á ÁO32 0.98
2.53
2.56
3.403(3) 148
3.461(4) 153
/
O1Ã
/
C5
113.8(3);
14.7(3)
111.2(4);
11.8(3)
114.0(2) 114.0(2) 114.6(1)
111.3(2) 110.9(2) 110.9(1)
#
5
1
C62Ã
/
H62CÁ Á ÁO32 0.98
/
C1Ã
/C2
#
6
1
Symmetry codes: #1, 3/2ꢂ
, 2ꢂz; #3, 2ꢂx, y, 2ꢂz; #4, 1/2ꢁ
/2ꢁy, 2ꢂz; #6, xꢂ1/2, 1/2ꢁy, z.
/
x, yꢂ
/
1/2, 1ꢂ
/
z; #2, 3/2ꢂ
/
x, yꢂ
/
1/
C5Ã
/
O1Ã
/
C1Ã
/
59.8(5):
63.1(4)
89.1(5);
92.5(4)
59.9(2)
76.6(2)
59.6(2)
75.5(2)
61.9(2)
75.8(2)
2
1
/
/
/
/
x, yꢂ
/
1/2, z; #5, 3/2ꢂ
/x,
O11
/
/
/
/
O1Ã
/
C1Ã
/
O11Ã
/C11
C1Ã
/
O11Ã
C11ÃC12
C1ÃO11Ã
C11ÃO12
/
179.0(5);
171.3(4)
ꢂ
/
ꢂ
/
ꢂ
/
Table 6
Hydrogen-bonding geometry (A, 8) for 11
˚
/
175.0(2) 174.3(2) 176.0(2)
/
/
1.1(1); ꢂ
10.4(7)
/
4.3(3) 5.2(3) 3.7(3)
D Ã
/
HÁ Á ÁA
d(D Ã
/
d(HÁ Á ÁA) d(DÁ Á ÁA) B
/
/
H)
(DHA)
Table 4
Hydrogen-bonding geometry (A, 8) for 9
N21Ã
#1
C5Ã
C6Ã
C32Ã
/
H21Á Á ÁO21
0.88
2.08
2.831(2) 143
˚
/
H5Á Á ÁO62 #2
1.00
2.43
2.35
2.59
3.370(3) 156
3.293(3) 159
3.349(3) 134
D Ã
/
HÁ Á ÁA
d(D Ã
/
d(HÁ Á ÁA) d(DÁ Á ÁA) B
/
/
H6AÁ Á ÁO42 #3 0.99
H)
(DHA)
/
H32AÁ Á ÁO1
0.98
#
4
N21Ã
/
H21Á Á ÁO22?
0.87(3) 2.19(3)
3.047(5) 169(5)
2.827(5) 164(5)
C62Ã
/
H62AÁ Á ÁO32 0.98
2.48
2.57
3.334(4) 145
3.526(3) 166
N21?Ã
/
H21?Á Á ÁO22 0.87(2) 1.98(2)
#
5
#1
C62Ã
/
H62CÁ Á ÁO32 0.98
C1?Ã
C4Ã
C5Ã
C32Ã
/
H1?Á Á ÁO32
1.00
2.57
2.52
2.56
2.49
3.517(7) 159
3.081(7) 115
3.234(7) 124
3.436(8) 163
#
6
/
H4Á Á ÁO62? #2 1.00
/
H5Á Á ÁO62? #2 1.00
Symmetry codes: #1, 1/2ꢂ
, 1ꢂz; #3, ꢂx, y, 1ꢂz; #4, xꢂ
y, 1ꢂz; #6, 1/2ꢁx, 1/2ꢁy, z.
/
x, yꢂ
/
1/2, 2ꢂ
/
z; #2, 1/2ꢂ
/
x, yꢂ
/
1/
/
H32AÁ Á ÁO62 0.98
2
2
/
/
/
/
1/2, yꢂ
/
1/2, z; #5, 1/2ꢂ
/
x, 1/
#3
ꢁ
/
/
/
/
C32?Ã
/
H32EÁ Á ÁO42 0.98
2.43
2.54
2.52
2.50
3.326(7) 152
3.484(7) 162
3.291(8) 136
3.422(8) 157
#4
C42?Ã
/
H42EÁ Á ÁO61 0.98
Table 7
Hydrogen-bonding geometry (A, 8) for 12
˚
#5
C62Ã
/
H62AÁ Á ÁO12? 0.98
D Ã
/
HÁ Á ÁA
d(D Ã
H)
/
d(HÁ Á ÁA) d(DÁ Á ÁA) B
/
#6
(DHA)
C62?ÃH62FÁ Á ÁO32 0.98
/
#5
N21ÃH21Á Á ÁO21
/
0.86(2) 2.05(2)
2.912(2) 174(2)
#
1
Symmetry codes: #1, x, yꢂ
yꢂ1/2, 2ꢂz; #4 ꢂx, y, ꢂz; #5, x, y, zꢂ
y, 2ꢂz.
/
1, z; #2, x, y, 1ꢁ
/
z; #3, 1/2ꢂ
/
x,
C5Ã
/
H5Á Á ÁO62 #2
1.00
2.42
2.31
2.49
3.371(3) 158
3.276(2) 164
3.370(2) 149
/
/
/
/
/
1; #6, 1/2ꢂ
/
x, 1/2ꢁ
/
C6Ã
/
H6AÁ Á ÁO42 #3 0.99
C32ÃH32BÁ Á ÁO1 0.98
/
/
#
4
3
. Experimental
C62Ã
/
H62AÁ Á ÁO32 0.98
2.55
2.40
3.382(3) 143
3.351(3) 165
#
5
C62Ã
/
H62CÁ Á ÁO32 0.98
3
.1. General methods
#
6
Melting points (mp) were determined on a B u¨ chi SMP
0 capillary melting-point apparatus and are uncor-
rected. Optical rotations were measured at 25 8C on a
Symmetry codes: #1, 1/2ꢂ
y, ꢂz; #3, ꢂx, y, ꢂz; #4, xꢂ
y, ꢂz; #6, 1/2ꢁx, 1/2ꢁy, z.
/
x, yꢂ
/
1/2, 1ꢂ
/
z; #2, 1/2ꢂ
/
x, 1/2ꢂ
/
2
/
/
/
/
1/2, yꢂ
/
1/2, z; #5, 1/2ꢂ
/
x, 1/2ꢁ
/
/
/
/

T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ
/
2128
2125
Fig. 7. The chain like arrangement of the normal intermolecular hydrogen bonds (dashed lines) in the crystal, here shown for
compound 10.
Fig. 8. Enlarged excerpt of the graphic given above for 10.
PerkinꢀElmer P341 polarimeter and are given in units
/
ꢂ1
2
of 10 deg cm g . Infrared spectra were recorded on
ꢂ1
1
a Perkinꢀ
NMR spectra were recorded on a Bruker DPX 400
400 MHz) spectrometer. The chemical shifts d (ppm)
/Elmer 1600 Series FT-IR instrument.
H
Fig. 9. The chain like arrangement of the normal intermole-
cular hydrogen bonds (dashed lines) in the crystal in the case of
compound 9.
(
are recorded relative to Me Si and the multiplicity of a
4
signal is designated by one of the following abbrevia-
tions: s, singlet; d, doublet; t, triplet; q, quartet; sep,
septet; and m, multiplet. All coupling constants values J
carbon atoms of the pyranose ring were assigned by
additional HMQC experiments using a Bruker DPX 400
spectrometer. The high-resolution mass spectra
(HRMS) were obtained on an AEI MS 50 spectrometer.
The spectrometer was operated at a source temperature
1
3
are in Hertz. C NMR spectra were recorded on a
Bruker DPX 400 (100 MHz) spectrometer. The spectra
were recorded with a broadband decoupled mode, and
the multiplicities obtained using a DEPT sequence. The

2126
T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ2128
/
3
.3. General procedure for N-acylation (6
/
8)
ꢀ
-Galactosamine hydrochloride (1),
Glassware was flame-dried under an Ar atmosphere and
allowed to cool. D
(1.0 equiv) in a methanolic NaOCH solution (0.5 M,
3
0.99 equiv) was stirred for 10 min at room temperature
(rt). The insoluble material was filtered off and the filter
was washed with dry MeOH (molecular sieve). To the
filtrate was added the appropriate acid anhydride 3
(
(
propionic anhydride), 4 (butyric anhydride) or 5
isobutyric anhydride), respectively (1.2 equiv), and the
mixture was stirred for 12 h under an Ar atmosphere.
The solution was evaporated under reduced pressure at
40 8C to leave a solid, which was stirred in dry EtOAc
(molecular sieve) for 1 h at rt. The solid was filtered off,
washed with dry EtOAc (molecular sieve) and dried in
vacuo. The obtained solid 6, 7, respectively 8 was used
without further purification.
Fig. 10. Enlarged excerpt of the graphic given above for 9.
3
.4. General procedure for O-acetylation (9
/
12)
ꢀ
allowed to cool. To the flask are added 2, 6, 7,
Glassware was flame-dried under an Ar atmosphere and
of 180 8C, and an ionizing potential of 70 eV. Perfluor-
okerosene was used as an internal calibration-standard.
Flash chromatography was carried out using Merck
respectively 8 (1.0 equiv), anhyd Py (67.0 equiv), Ac O
2
(33.5 equiv) and a catalytic amount of 4-dimethylami-
nopyridine (DMAP). The mixture was stirred for 24 h at
silica gel 60 (230ꢀ400 mesh), CHCl from Fisher, and
/
3
MeOH from Acros. Thin-layer chromatography (TLC)
was carried out on commercially available pre-coated
aluminum plates (Merck silica gel 60 silica). Spots were
rt, diluted with CHCl and extracted 2 times with aq 1.0
3
M HCl. The organic phase was separated and the
combined aqueous phases extracted 2 times with
CHCl . The combined organic phases were washed 2
2
8
visualized with K a¨ giꢀMiescher solution.
/
3
times with cold, satd aq NaHCO , dried (Na SO ),
3
2
4
concentrated, and dried in vacuo. The crude product
was purified by flash chromatography on silica, eluted
3
.2. X-ray measurements, determination and refinement
with CHCl3ꢀ
/
MeOH (30:1 for 9, 40:1 for 10ꢀ12) to give
/
Crystallographic measurements were carried out on a
Bruker Nonius Kappa-CCD diffractometer using gra-
an anomeric mixture of the title compound as a solid.
Recrystallization from EtOAc afforded colourless
phite monochromatized Mo K radiation (lꢃ
/
0.71073
A) at 123 K. The structures were solved by direct
a
crystals of 9ꢀ
/
12 suitable for X-ray analysis.
˚
2
methods using SHELXS and refined on F , by full
9
2
3.5. 1,3,4,6-Tetra-O-acetyl-2-(acetylamino)-2-deoxy-a-
3
0
, with no
matrix least-squares procedures using SHELXL
absorption correction. The Friedel pairs of 11 were
merged prior to the final refinement. The absolute
D-galactopyranoside (9)
Mp 183ꢀ
/
184 8C (EtOAc), Lit. 33 182ꢀ
/
183 8C (CHCl3ꢀ
/
3
1
configuration of the title compounds could not be
determined by the X-ray data but is fixed by the
absolute stereochemistry of the starting material N-
Et O), Lit. 34 178 8C (EtOHꢀ
/
petroleum ether), 169ꢀ
/
2
171 8C (EtOH); [a]D
ꢁ
/
968 (c 0.25, CHCl ), Lit. 33 ꢁ
/
3
1028 (c 3.2, CHCl ), Lit. 34 ꢁ
/
1028 (c 1.6, CHCl ), Lit.
3
3
acetyl-
D
-galactosamine and
D-galactosamine-hydro-
35 ꢁ
CÄO, ester), 1658 (amide I), 1563 (amide II), 1436, 1375,
1256, 1221, 1127, 1043, 1011, 940 and 682 cm ; H
NMR (400 MHz, d -Py): d 9.14 (d, 1 H, J 8.5, NH),
/
978 (c 1.0, CHCl ); IR (KBr): 3300, 2925, 1749 (n
3
chloride, respectively. The position of the amide H
atom of 9, 10 and 12 were determined from a difference
Fourier map and the coordinates were refined freely,
with isotropic displacement parameter constrained to
/
ꢂ1
1
5
NH,2
6.86 (d, 1 H, J1,2 3.5, H-1), 5.89 (dd, 1 H, J4,3 3.3, J4,5
1.1, H-4), 5.74 (dd, 1 H, J3,2 11.9, H-3), 5.33 (ddd, 1 H,
H-2), 4.64 (ddd, 1 H, J6?,5 6.6, J6,5 6.5, H-5), 4.40 (dd, 1
H, J6?,6 11.2, H-6?), 4.31 (dd, 1 H, H-6), 2.06 (s, 3 H,
CH ), 2.03 (s, 3 H, CH ), 2.02 (s, 3 H, CH ), 1.89 (s, 3 H,
U (H)ꢃ1.2U (N) or free (10). All remaining H atoms
/
iso
eq
were treated as riding, with CÃ
/
Hꢃ
/
0.98ꢀ
/
1.00 and NÃ
/
˚
Hꢃ/0.88
A
.5U (CH ) and 1.2U (NH) (11). The hydrogen-bond-
(11). U (H)ꢃ1.2U (CH, CH ),
/
iso
eq
2
1
ing geometry and the symmetry codes were determined
eq
3
eq
3
3
3
CH ), 1.86 (s, 3 H, CH ), Lit. 35 coupling constants are
3 3
13
in a good agreement (400 MHz, CDCl3); C NMR (100
3
.
2
using PLATON

T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ
/
2128
2127
MHz, d -Py): d 170.8 (CO), 170.6 (CO), 170.6 (CO),
5
3.8. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-(2-methyl-
propanoylamino)-a- -galactopyranoside (12)
1
3
70.2 (CO), 169.4 (CO), 92.0 (C-1), 69.2 (C-5), 68.5 (C-
), 67.7 (C-4), 61.9 (C-6), 47.5 (C-2), 22.7 (CH ), 20.6
D
3
(
m/z Calcd for [C H NO ]H : 390.1400. Found:
CH ), 20.5 (CH ), 20.4 (CH ), 20.3 (CH ); EI-HRMS
ꢁ
Mp 180ꢀ
IR (KBr): 3313, 2975, 1752 (n CÄ
I), 1540 (amide II), 1434, 1374, 1243, 1215, 1133, 1092,
/
181 8C (EtOAc); [a]D
ꢁ
/
888 (c 0.25, CHCl3);
3
3
3
3
/O, ester), 1653 (amide
1
6
23
10
3
5
90.1376; Anal. Calcd for C H NO : C, 49.36; H,
16 23 10
ꢂ1
1
.95; N, 3.60. Found: C, 48.91; H, 5.97; N, 3.56.
1046, 1010, 934, 821, 759 and 713 cm ; H NMR (400
MHz, d -Py): d 8.92 (d, 1 H, J 8.6, NH), 6.86 (d, 1
5
NH,2
H, J1,2 3.7, H-1), 5.90 (dd, 1 H, J4,3 3.2, J4,5 1.1, H-4),
.76 (dd, 1 H, J3,2 11.9, H-3), 5.33 (ddd, 1 H, H-2), 4.64
ddd, 1 H, J6?,5 6.6, J6,5 6.6, H-5), 4.39 (dd, 1 H, J6?,6
1.2, H-6?), 4.31 (dd, 1 H, H-6), 2.67 (sep, 1 H, JHH 6.8,
CH(CH ) ), 2.03 (s, 3 H, CH ), 2.00 (s, 3 H, CH ), 1.89
3
(
.6. 1,3,4,6-Tetra-O-acetyl-2-deoxy-2-
propanoylamino)-a-D-galactopyranoside (10)
5
(
1
Mp 202ꢀ
IR (KBr): 3310, 2987, 1750 (n CÄ
I), 1549 (amide II), 1434, 1374, 1242, 1217, 1133, 1047,
/
203 8C (EtOAc); [a]D
ꢁ
/
898 (c 0.25, CHCl3);
3
2
3
3
/O, ester), 1650 (amide
(s, 3 H, CH ), 1.88 (s, 3 H, CH ), 1.19 (d, 3 H,
CH(CH ) ), 1.18 (d, 3 H, CH(CH ) ); C NMR (100
3 3
1
3
ꢂ1
1
3 2
3 2
8
9
5
1
24, 761 and 711 cm ; H NMR (400 MHz, d -Py): d
5
MHz, d -Py): d 178.1 (CO), 170.6 (CO), 170.6 (CO),
5
.02 (d, 1 H, JNH,2 8.5, NH), 6.86 (d, 1 H, J1,2 3.7, H-1),
.90 (dd, 1 H, J4,3 3.2, J4,5 0.9, H-4), 5.75 (dd, 1 H, J3,2
1.8, H-3), 5.34 (ddd, 1 H, H-2), 4.64 (ddd, 1 H, J6?,5 6.6,
1
3
70.2 (CO), 169.4 (CO), 91.9 (C-1), 69.3 (C-5), 68.6 (C-
), 67.7 (C-4), 61.9 (C-6), 47.3 (C-2), 35.1 (CH,
CH(CH ) ), 20.6 (CH ), 20.5 (CH ), 20.4 (CH ), 20.3
3
3
2
3
3
J6,5 6.6, H-5), 4.40 (dd, 1 H, J6?,6 11.2, H-6?), 4.31 (dd, 1
H, H-6), 2.35 (q, 2 H, JHH 7.5, CH CH ), 2.03 (s, 3 H,
CH ), 2.02 (s, 3 H, CH ), 1.89 (s, 3 H, CH ), 1.87 (s, 3 H,
(
CH ), 20.0 (CH ), 19.8 (CH ); EI-HRMS m/z Calcd for
3 3 3
2
3
ꢁ
[C H NO ] : 417.1635. Found: 417.1649; Anal.
18 27 10
Calcd for C H NO : C, 51.79; H, 6.52; N, 3.36.
3
3
3
1
3
18 27
10
CH ), 1.16 (t, 3 H, CH CH ); C NMR (100 MHz, d5-
3
2
3
Found: C, 51.48; H, 6.42; N, 3.23.
Py): d 174.8 (CO), 170.6 (CO), 170.6 (CO), 170.2 (CO),
1
6
2
69.4 (CO), 92.0 (C-1), 69.2 (C-5), 68.5 (C-3), 67.7 (C-4),
1.9 (C-6), 47.4 (C-2), 29.3 (CH , CH CH ), 20.6 (CH ),
2
2
3
3
0.5 (CH ), 20.4 (CH ), 20.3 (CH ), 10.3 (CH ,
3
4. Supplementary material
3
3
3
ꢁ
CH CH ); EI-HRMS m/z Calcd for [C H NO ] :
17 25
2
3
10
4
C H NO : C, 50.62; H, 6.25; N, 3.47. Found: C,
03.1478. Found: 403.1476; Anal. Calcd for
Supplementary material is available at the Cambridge
Crystallographic Data Center (CCDC) for the title
compounds 9 (CCDC 189829), 10 (CCDC 189830), 11
1
7
23
10
5
0.02; H, 6.21; N, 3.16.
(CCDC 189831), and 12 (CCDC 208437). These crystal-
lographic data may be obtained free of charge from The
Director, CCDC, 12 Union Road, Cambridge, CB2
3.7. 1,3,4,6-Tetra-O-acetyl-2-(butanoylamino)-2-deoxy-
a-D-galactopyranoside (11)
1
EZ, UK (Fax: ꢁ44-1223-336-033; e-mail: deposit@
/
ccdc.cam.ac.uk or www: http://www.ccdc.cam.ac.uk/
conts/retrieving.html).
Mp 185ꢀ
IR (KBr): 3309, 2974, 1749 (n CÄ
I), 1548 (amide II), 1435, 1374, 1244, 1216, 1133, 1085,
/
186 8C (EtOAc); [a]D
ꢁ
/
898 (c 0.25, CHCl3);
/O, ester), 1645 (amide
ꢂ1
1
1
MHz, d -Py): d 9.02 (d, 1 H, J 8.6, NH), 6.86 (d, 1
037, 1009, 927, 824, 760 and 711 cm ; H NMR (400
5
NH,2
Acknowledgements
H, J1,2 3.5, H-1), 5.90 (dd, 1 H, J4,3 3.2, J4,5 1.1, H-4),
.75 (dd, 1 H, J3,2 11.8, H-3), 5.35 (ddd, 1 H, H-2), 4.64
ddd, 1 H, J6?,5 6.7, J6,5 6.6, H-5), 4.40 (dd, 1 H, J6?,6
1.2, H-6?), 4.31 (dd, 1 H, H-6), 2.33 (t, 2 H, JHH 7.2,
CO)CH ), 2.05 (s, 3 H, CH ), 2.01 (s, 3 H, CH ), 1.89
5
(
1
(
(
The authors wish to thank Professor Dr K. Sandhoff
(Bonn) and the Deutsche Forschungsgemeinschaft (SFB
284) for financial support.
2
3
3
s, 3 H, CH ), 1.88 (s, 3 H, CH ), 1.72 (m, 2 H,
3
3
1
3
CH CH ), 0.85 (t, 3 H, J
3
7.4, CH CH ); C NMR
2 3
2
HH
References
(
(
100 MHz, d -Py): d 173.9 (CO), 170.6 (CO), 170.6
5
CO), 170.2 (CO), 169.4 (CO), 92.0 (C-1), 69.2 (C-5),
1
. Varki, A.; Cummings, R.; Esko, J.; Freeze, H.; Hart, G.;
Marth, J. Essentials of Glycobiology; Cold Spring Harbor
Laboratory Press: New York, 1999.
6
8.5 (C-3), 67.7 (C-4), 61.9 (C-6), 47.3 (C-2), 38.1 (CH2,
CO)CH ), 20.6 (CH ), 20.5 (CH ), 20.4 (CH ), 20.3
(
(
2
3
3
3
CH ), 19.6 (CH , CH CH ), 13.7 (CH , CH CH ); EI-
3
2
2
3
3
2
3
2
. Keppler, O. T.; Horstkorte, R.; Pawlita, M.; Schmidt, C.;
ꢁ
HRMS m/z Calcd for [C H NO ] : 417.1635.
10
1
8
27
Reutter, W. Glycobiology 2001, 11, 11Rꢀ
3. Bertozzi, C. R. Science 2001, 291, 2357ꢀ2364.
4. Brodesser, S.; Sawatzki, P.; Kolter, T. Eur. J. Org. Chem.
2003, 2021ꢀ2034.
/18R.
Found: 417.1649; Anal. Calcd for C H NO : C,
1
8
27
10
/
5
3
1.79; H, 6.52; N, 3.36. Found: C, 51.63; H, 6.47; N,
.27.
/

2128
T. Mikeska et al. / Carbohydrate Research 338 (2003) 2119ꢀ2128
/
5
. Kayser, H.; Zeitler, R.; Kannicht, C.; Grunow, D.; Nuck,
R.; Reutter, W. J. Biol. Chem. 1992, 267, 16934ꢀ
6938.
. Kolter, T.; Sandhoff, K. Angew. Chem., 1999, 111, 1633ꢀ
670; Angew. Chem. Int. Ed. 1999, 38, 1532ꢀ1568.
. Kolter, T.; Proia, R. L.; Sandhoff, K. J. Biol. Chem. 2002,
77, 25859ꢀ25862.
. Furukawa, K.; Takamiya, K.; Furukawa, K. Biochim.
Biophys. Acta 2002, 1573, 356ꢀ362.
19. Luger, P.; Buschmann, J.; Schmidt, H.-J. Acta Crystal-
logr., Sect. B 1982, 38, 2732ꢀ2735.
20. Clayden, J.; Greeves, N.; Warren, S.; Wothers, P. Organic
/
/
1
6
7
8
9
/
Chemistry; Oxford University Press: Oxford, 2001; pp
1
/
1133ꢀ
21. Jeffrey, G. A. Acta Crystallogr., Sect. B 1990, 46, 89ꢀ
22. Juaristi, E.; Cuevas, G. Tetrahedron 1992, 48, 5019ꢀ5087.
23. Tvaro sˇ ka, I; Bleha, T. Adv. Carbohydr. Chem. Biochem.
1989, 47, 45ꢀ123.
/
1134.
/103.
2
/
/
/
/
. Wendeler, M.; Reilaender, H.; Hoernschemeyer, J.;
Schwarzmann, G.; Kolter, T.; Sandhoff K. Recognition
of Carbohydrates in Biological Systems. In: Lee, Y. C.;
Lee, R. T. (Eds.), Methods in Enzymology (in press).
24. Allen, F. H.; Kennard, O.; Watson, D. G.; Brammer, L.;
Orpen, A. G.; Taylor, R. J. Chem. Soc. Perkin Trans. 2
1987, S1ꢀ
25. Lemieux, R. U.; Pavia, A. A.; Martin, J. C.; Watanabe, K.
A. Can. J. Chem. 1969, 47, 4427ꢀ4439.
/
S19.
1
1
1
1
1
1
0. Sarkar, A. K.; Fritz, T. A.; Taylor, W. H.; Esko, J. D.
Proc. Natl. Acad. Sci. USA 1995, 92, 3323ꢀ3327.
1. Jacobs, C. L.; Mahal, L. K.; Yarema, K. J.; Nauman, D.;
Bertozzi, C. R. Methods Enzymol. 2000, 327, 260ꢀ275.
2. Hang, H. C.; Bertozzi, C. R. J. Am. Chem. Soc. 2001, 123,
242ꢀ1243.
3. Inouye, Y.; Onodera, K.; Kitaoka, S.; Hirano, S. J. Am.
Chem. Soc. 1956, 78, 4722ꢀ4724.
4. Paulsen, H.; H o¨ hne, H. Carbohydr. Res. 1977, 58, 484ꢀ
87.
/
/
26. Asensio, J. L.; Canada, F. J.; Garcia-Herrero, A.; Murillo,
M. T.; Fernandez-Mayoralas, A.; Johns, B. A.; Kozak, J.;
Zhu, Z. Z.; Johnson, C. R.; Jim e´ nez-Barbero, J. J. Am.
/
Chem. Soc. 1999, 121, 11318ꢀ
27. Steiner, T. Angew. Chem. Int. Ed. 2002, 41, 48ꢀ
28. Miescher, K. Helv. Chim. Acta 1946, 29, 743ꢀ752.
29. Sheldrick, G. M. Acta Crystallogr., Sect. A 1990, 46, 467ꢀ
/11329.
1
/
/
76.
/
/
/
/
473.
4
30. Sheldrick, G. M., SHELXL97, University of G o¨ ttingen,
Germany, 1997.
5. (a) Sheldrick, G. M., SHELXLTL-Plus, University of
G o¨ ttingen, Germany, 1991;
31. Flack, H. D. Acta Crystallogr., Sect. A 1983, 39, 876ꢀ881.
/
(
b) Farrugia, L. J. J. Appl. Cryst. 1997, 30, 565.
6. Neuman, A.; Gillier-Pandraund, H.; Longchambon, F.;
Rabinovich, D. Acta Crystallogr., Sect. B 1975, 31, 474ꢀ
77.
7. Gilardi, R. D.; Flippen, J. L. Acta Crystallogr., Sect. B
974, 30, 2931ꢀ2933.
8. Kim, S. H.; Jeffrey, G. A. Acta Crystallogr. 1967, 22,
37ꢀ545.
32. Spek, A. L., PLATON, University of Utrecht, The Nether-
lands, 2002.
33. Hudson, C. S.; Dale, J. K. J. Am. Chem. Soc. 1916, 38,
1
/
4
1431ꢀ
/
1436.
1
1
34. Stacey, M. J. Chem. Soc. 1944, 272ꢀ274.
/
1
/
35. Chaplin, D.; Crout, D. H. G.; Bornemann, S.; Hutch-
inson, D. W.; Khan, R. J. Chem. Soc. Perkin Trans. 1
5
/
1992, 235ꢀ237.
/