Hydrogen bonding in crystal forms of primary amide functionalised glucose and cellobiose

Article abstract of DOI:10.1016/j.carres.2013.03.024

A glucoside and cellobioside of glycolamide were synthesised and the crystal chemistry of these compounds investigated. The amidoglucoside crystallised in the P2₁ space group. The primary amide group participates in C(7) and C(17) chains also involving the pyranose oxygen and hydroxyl groups. The amidocellobioside crystallised as a methanol solvate in the P2₁ space group. The amide N-H groups donate hydrogen bonds to oxygen atoms on the cellobiose units, while intramolecular hydrogen bonds give rise to S(7) and S(9) motifs in addition to a R33 (9) motif. A tetra-O-acetylglucoside derivative of thioglycolamide and its sulfoxide derivative were synthesised to examine the effect of protecting the glucopyranose hydroxyl groups. The thioglycolamido derivative, which crystallised in the P2₁2₁2₁ space group, featured amide N-H groups donating to the glucopyranose oxygen and an acetyloxy group. The sulfoxy derivative crystallised in the P2₁ space group and featured the primary amide groups forming R23(8) motifs generating a 2 ₁ ladder.

Full text of DOI:10.1016/j.carres.2013.03.024

Carbohydrate Research 374 (2013) 29–39
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Hydrogen bonding in crystal forms of primary amide functionalised
glucose and cellobiose
a,
⇑
a
a
b
a
Humphrey A. Moynihan , John A. Hayes , Kevin S. Eccles , Simon J. Coles , Simon E. Lawrence
a
Department of Chemistry/Analytical and Biological Chemistry Research Facility, University College Cork, College Road, Cork, Ireland
UK National Crystallographic Service, School of Chemistry, University of Southampton, Highfield, Southampton SO17 1BJ, UK
b
a r t i c l e i n f o
a b s t r a c t
Article history:
A glucoside and cellobioside of glycolamide were synthesised and the crystal chemistry of these com-
pounds investigated. The amidoglucoside crystallised in the P2 space group. The primary amide group
participates in C(7) and C(17) chains also involving the pyranose oxygen and hydroxyl groups. The
amidocellobioside crystallised as a methanol solvate in the P2 space group. The amide N–H groups
Received 23 January 2013
Received in revised form 8 March 2013
Accepted 23 March 2013
Available online 2 April 2013
1
1
donate hydrogen bonds to oxygen atoms on the cellobiose units, while intramolecular hydrogen bonds
3
give rise to S(7) and S(9) motifs in addition to a R3 (9) motif. A tetra-O-acetylglucoside derivative of thio-
Keywords:
Glucose
Cellobiose
Primary amides
Crystal engineering
glycolamide and its sulfoxide derivative were synthesised to examine the effect of protecting the gluco-
pyranose hydroxyl groups. The thioglycolamido derivative, which crystallised in the P2
1 1 1
2 2 space group,
featured amide N–H groups donating to the glucopyranose oxygen and an acetyloxy group. The sulfoxy
3
derivative crystallised in the P2
motifs generating a 2 ladder.
1
space group and featured the primary amide groups forming R
(8)
2
1
Ó 2013 Elsevier Ltd. All rights reserved.
1
. Introduction
Crystal engineering is the control of molecular assembly in crys-
hols, acetals and ketals, have not been widely exploited in crystal
engineering. The crystal chemistry of sugars generally focuses on
features such as pyranose ring puckering characterised by Cre-
7
tals with the ultimate aim of controlling properties which arise from
the collective participation of molecules in the crystalline array such
as density, melting point, solubility, mechanical and thermal charac-
teristics. For sugars and carbohydrates, these crystal state proper-
ties affect activities such as hygroscopicity, flow, blending,
compression into tablets and other operations of commercial impor-
mer–Pople parameters, torsional angles for primary hydroxyls
8
and acetal linkages and conformational or supramolecular features
specific to classes of monosaccharide or polysaccharide.9
1
Carefully designed structural modifications can be used to pro-
vide insights into physical or crystallographic aspects of sugars.
For example, modified sugars can provide information of the details
2
10
tance. An ability to control the molecular assembly of sugar mole-
of enzyme-sugar binding, can act as models for complex biomole-
1
1
cules in crystalline solids in a rational manner would have
applications in areas such as pharmaceutical formulation using su-
gar-derived excipients. Crystal engineering exploits ‘supramolecu-
lar synthons’, these being structural units within crystals which
assemble by known intermolecular interactions.3 Amides, which
form well known hydrogenbonded motifs in the solid state, are good
examples of such synthons. In particular, primary amide groups are
associated with important supramolecular motifs often occurring in
crystal structures, such as dimers and ‘amide ladders’. These motifs
are conveniently described using the notation devised by Etter, for
cules or can provide information on interactions between sugar-
1
2
based groups. The work described herein aims to investigate
whether incorporation of conventional supramolecular synthons,
in particular primary amides, into sugars gives rise to motifs such
2
2
as R (8) dimers, which could be used as a basis for crystal engineer-
ing; or whether alternatively, the hydrogen bonding capabilities of
the sugar and amide group form new exploitable motifs. To achieve
this aim, a short series of primary amido-functionalised glucose and
cellobiose derivatives have been prepared and the crystal chemistry
of these determined. These molecules are designed to have distinct
sugar and amide domains in contrast to, for example, N-acetylgluco-
samine, in which the amide group is directly substituted on the glu-
copyranose ring. Crystallisation and crystal structure determination
of the resulting primary amide functionalised glucose and cellobiose
compounds were then carried out to probe the hydrogen bonding
networks thus formed.
4
5
2
example the common amide dimer motif can be described as an R
2
6
(
8) dimer. The functional groups generally present in sugars: alco-
⇑
Corresponding author. Tel.: +353 21 4902488; fax: +353 21 4274097.
E-mail address: h.moynihan@ucc.ie (H.A. Moynihan).
0
008-6215/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2013.03.024

3
0
H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
2
2
. Results and discussion
2.2. Crystal structures of primary amide functionalised glucose
and cellobiose 7
3
.1. Preparation of primary amide functionalised glucose and
cellobiose derivatives
Crystals of compounds 3 and 7 suitable for analysis by single-
crystal X-ray diffraction were grown by slow evaporation of solu-
tions in ethanol and methanol respectively. Both compounds crys-
Primary amide functionalised derivatives of glucose and cellobi-
ose were synthesised from the corresponding trichloroacetimi-
dates as outlined in Scheme 1, that is, by conversion of the
trichloroacetimidates 1 and 5 to the corresponding methyl glyco-
late derivates 2 and 6, followed by treatment of these with ammo-
nia in methanol to give the required primary amide functionalised
glucose and cellobiose derivatives, 3 and 7, respectively.
1
tallised in the monoclinic P2 space group. Crystallographic data
are given in Table 1. Table 2 gives the hydrogen bond data obtained
1
3
from Platon.
The glucopyranose ring of compound 3 adopts a 4C
1
conforma-
tion with the corresponding Cremer–Pople parameters given in Ta-
ble 3. These values are close to the corresponding values for an
7
ideal cyclohexane chair (Q = 0.63 Å, h = 5.0°). The dihedral angle
OAc
OAc
OH
O
a
AcO
AcO
b
O
AcO
AcO
O
O
CO Me
HO
HO
2
O
CONH2
AcO
O
CCl3
AcO
OH
1
NH
2
3
OAc
OAc
OAc
OAc
O
c, d
AcO
AcO
O
AcO
O
O
O
OAc
AcO
AcO
AcO
O
AcO
AcO
OAc
OAc
AcO
O
CCl3
4
5
NH
a
OH
OH
O
OAc
OAc
O
HO
HO
O
b
O
O
O
CONH2
O
AcO
HO
AcO
O
CO Me
2
OH
AcO
OH
OAc
7
6
Scheme 1. Reagents and conditions: (a) HOCH
0 min then rt, 12 h.
2
CO
2
Me, BF
3
ꢀEt
2
O, CH
2
Cl
2
, ꢁ25 °C, 4–5 h; (b) 2 M NH
3
2
in MeOH, rt, 1 h; (c) BnNH , THF, rt, 12 h; (d) CCl
3 2 2
CCN, DBU, CH Cl , 0 °C,
3
Table 1
Crystallographic data
Compound reference
3
7
9
10
Chemical formula
Formula mass
Crystal system
a (Å)
b (Å)
c (Å)
C
8
H
15NO
7
C
15
H
29NO13
C
16
H
23NO10
S
16
C H23NO11S
437.41
237.21
Monoclinic
5.5981(8)
431.39
Monoclinic
9.651(3)
421.41
Orthorhombic
7.3864(9)
13.496(2)
20.100(3)
90
Monoclinic
9.1221(9)
5.5092(5)
21.085(2)
91.474 (6)
6.9551(9)
8.387(3)
13.5890(17)
101.378(4)
518.69(12)
12.638(5)
105.322(13)
986.6(6)
b (°)3
V (Å )
2003.7(5)
Mo K
1059.29(17)
Mo K
Radiation used
Crystal size (mm)
Temperature/K
Space group
Mo K
a
Mo K
a
a
a
0.45 ꢂ 0.32 ꢂ 0.22
0.11 ꢂ 0.09 ꢂ 0.06
0.47 ꢂ 0.23 ꢂ 0.17
0.20 ꢂ 0.01 ꢂ 0.01
300(2)
296(2)
300(2)
100(2)
P2
1
P2
1
P2
1
2
1
2
1
P2
1
Z
l
2
2
4
2
(mm 1
ꢁ
)
0.134
0.128
0.215
0.209
No. of reflections measured
No. of independent reflections
3715
2038
10491
3813
19356
3823
5623
4311
R
int
0.0199
0.0345
0.0840
0.0399
0.0878
1.055
0.0908
0.0534
0.0758
0.1380
0.0976
0.950
0.0283
0.0297
0.0864
0.0367
0.1005
1.123
0.0352
0.0739
0.1131
0.0532
0.1131
1.044
Final R
Final wR(F ) values (I > 2
Final R values (all data)
Final wR(F ) values (all data)
Goodness of fit on F2
Flack parameter
1
values (I > 2r(I))
2
r
(I))
1
2
ꢁ1.8(11)
1.7(15)
ꢁ0.01(7)
ꢁ0.10(11)

H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
31
Table 2
Hydrogen bond data.
Donor–Hꢀ ꢀ ꢀacceptor
ARU
D–H
Hꢀ ꢀ ꢀA
Dꢀ ꢀ ꢀA
D–Hꢀ ꢀ ꢀA
Compound 3
N(11)–H(11A)ꢀ ꢀ ꢀO(6)
N(11)–H(11B)ꢀ ꢀ ꢀO(7)
O(12)–H(12)ꢀ ꢀ ꢀO(16)
O(13)–H(13)ꢀ ꢀ ꢀO(14)
O(13)–H(13)ꢀ ꢀ ꢀO(12)
O(14)–H(14)ꢀ ꢀ ꢀO(13)
O(16)–H(16)ꢀ ꢀ ꢀO(10)
C(3)–H(3)ꢀ ꢀ ꢀO(14)
C(5)–H(5)ꢀ ꢀ ꢀO(13)
C(8)–H(8A)ꢀ ꢀ ꢀO(6)
C(8)–H(8A)ꢀ ꢀ ꢀO(10)
C(15)–H(15A)ꢀ ꢀ ꢀO(14)
ꢁx, 0.5 + y, 1ꢁz
Intramolecular
ꢁ1 + x, 1 + y, z
0.87(3)
0.87(3)
0.82
0.82
0.82
0.82
0.82
0.98
0.98
2.18(3)
2.26(3)
2.16
2.56
2.08
1.86
1.96
2.32
2.45
3.021(3)
2.648(3)
2.851(2)
2.8866(18)
2.8743(19)
2.6683(18)
2.768(2)
3.269(2)
3.398(2)
2.816(2)
3.456(3)
2.984(2)
162(3)
107(2)
142
105
162
168
171
163
164
Intramolecular
ꢁx, ꢁ0.5 + y, 2 – z
ꢁx, ꢁ0.5 + y, 2 – z
1 ꢁ x, ꢁ0.5 + y, 1 ꢁ z
1ꢁx, 0.5 + y, 2 ꢁ z
1 + x, y, z
Intramolecular
1 ꢁ x, ꢁ0.5 + y, 1 ꢁ z
Intramolecular
0.97
0.97
0.97
2.43
2.51
2.59
104
166
105
Compound 7
N(9)–H(9A)ꢀ ꢀ ꢀO(24)
N(9)–H(9B)ꢀ ꢀ ꢀO(7)
N(9)–H(9B)ꢀ ꢀ ꢀO(12)
O(11)–H(11)ꢀ ꢀ ꢀO(12)
O(12)–H(12)ꢀ ꢀ ꢀO(13)
O(12)–H(12)ꢀ ꢀ ꢀO(19)
O(20)–H(20)ꢀ ꢀ ꢀO(22)
O(21)–H(21)ꢀ ꢀ ꢀO(28)
O(22)–H(22)ꢀ ꢀ ꢀO(26)
O(24)–H(24)ꢀ ꢀ ꢀO(11)
O(26)–H(26)ꢀ ꢀ ꢀO(21)
O(28)–H(28)ꢀ ꢀ ꢀO(10)
C(2)–H(2)ꢀ ꢀ ꢀO(24)
C(5)–H(5)ꢀ ꢀ ꢀO(20)
1 ꢁ x, 1.5 + y, 1 ꢁ z
Intramolecular
1 ꢁ x, 0.5 + y, 1ꢁz
1 ꢁ x, 0.5 + y, 1 ꢁ z
Intramolecular
Intramolecular
2 ꢁ x, 0.5 + y, 2 ꢁ z
1 ꢁ x, ꢁ0.5 + y, 2 ꢁ z
2 ꢁ x, ꢁ0.5 + y, 2 ꢁ z
1 ꢁ x, ꢁ0.5 + y, 1 ꢁ z
x, 1 + y, z
0.86
0.86
0.86
0.82
0.82
0.82
0.81(5)
0.82
0.82
0.82
0.82
0.82
0.98
0.98
2.26
2.27
2.39
1.95
2.56
1.95
2.05(5)
1.91
1.93
2.08
1.94
1.87
2.60
2.59
3.079(4)
2.653(4)
3.185(5)
2.728(4)
2.944(4)
2.762(4)
2.837(5)
2.724(5)
2.748(4)
2.882(4)
2.716(4)
2.599(6)
3.516(5)
3.175(6)
159
107
153
157
110
169
167(5)
173
177
165
158
148
156
118
x, ꢁ1 + y, z
x, 1 + y, z
1 ꢁ x, 0.5 + y, 2 ꢁ z
Compound 9
N(11)–H(11A)ꢀ ꢀ ꢀO(6)
N(11)–H(11B)ꢀ ꢀ ꢀO(14)
C(2)–H(2)ꢀ ꢀ ꢀO(14)
C(2)–H(2)ꢀ ꢀ ꢀO(10)
C(3)–H(3)ꢀ ꢀ ꢀO(18)
C(4)–H(4)ꢀ ꢀ ꢀO(22)
C(15)–H(15B)ꢀ ꢀ ꢀO(22)
C(19)–H(19C)ꢀ ꢀ ꢀO(12)
C(23)–H(23A)ꢀ ꢀ ꢀO(27)
C(24)–H(24B)ꢀ ꢀ ꢀO(10)
C(28)–H(28B)ꢀ ꢀ ꢀO(22)
ꢁ0.5 + x, 2.5 ꢁ y, ꢁz
ꢁ1 + x, y, z
0.86
0.86
0.98
0.98
0.98
0.98
0.96
0.96
0.96
0.97
0.96
2.24
2.15
2.32
2.47
2.35
2.31
2.46
2.56
2.51
2.58
2.39
3.045(2)
2.978(3)
2.719(3)
3.330(3)
2.725(3)
2.686(2)
3.289(3)
3.438(3)
3.461(4)
3.331(3)
3.295(4)
155
163
104
146
102
102
145
152
171
134
157
Intramolecular
0.5 + x, 2.5 ꢁ y, ꢁz
Intramolecular
Intramolecular
0.5 ꢁ x, 2 ꢁ y, ꢁ0.5 + z
0.5 + x, 1.5 ꢁ y, ꢁz
ꢁx, ꢁ0.5 + y, 0.5 ꢁ z
ꢁ0.5 + x, 2.5 ꢁ y, ꢁz
ꢁ1 + x, y, z
Compound 10
N(1)–H(1A)ꢀ ꢀ ꢀO(3)
N(1)–H(1B)ꢀ ꢀ ꢀO(2)
C(2)–H(2)ꢀ ꢀ ꢀO(11)
C(3)–H(3)ꢀꢀꢀO(9)
1 ꢁ x, 0.5 + y, 1 ꢁ z
x, 1 + y, z
0.88
0.88
1.00
1.00
1.00
1.00
0.99
0.98
0.98
0.98
0.98
0.98
1.99
2.29
2.25
2.25
2.30
2.37
2.08
2.56
2.60
2.50
2.47
2.51
2.871(4)
3.074(4)
2.646(4)
2.701(5)
2.725(4)
3.346(4)
3.007(4)
3.501(5)
3.406(5)
3.440(5)
3.284(5)
3.315(5)
175
149
102
106
104
165
156
161
140
161
140
139
Intramolecular
Intramolecular
Intramolecular
x, ꢁ1 + y, z
C(4)–H(4)ꢀ ꢀ ꢀO(7)
C(5)–H(5)ꢀ ꢀ ꢀO(7)
C(6)–H(6B)ꢀ ꢀ ꢀO(2)
C(10)–H(10A)ꢀ ꢀ ꢀO(5)
C(10)–H(10B)ꢀ ꢀ ꢀO(5)
C(12)–H(12B)ꢀ ꢀ ꢀO(5)
C(14)–H(14A)ꢀ ꢀ ꢀO(2)
C(14)–H(14B)ꢀ ꢀ ꢀO(9)
x, 1 + y, z
1 ꢁ x, ꢁ0.5 + y, ꢁz
x, ꢁ1 + y, z
ꢁ1 + x, y, z
ꢁ1 + x, 1 + y, z
x, 1 + y, z
Table 3
chains consisting of a repeat unit containing 7 atoms. The amide
oxygen also accepts a hydrogen bond from the primary hydroxyl,
forming a C(17) chain with two molecules in the repeat unit (Figs. 3
and 4). It should be noted that while crystallisation from ethanol
gave crystals (melting point 155.0 °C by DSC) of compound 3 suit-
able for single-crystal XRD, crystallisation from methanol gave
crystals of melting point 165.5 °C (DSC), possibly another crystal
form such as a polymorph or solvate. However these latter crystals
were highly agglomerated and were not suitable for single-crystal
analysis.
Cremer–Pople ring puckering coordinates
Compound
Q (Å)
h (°)
u (°)
3
0.573(18)
0.574(4)
0.605(2)
0.575(19)
0.563(3)
8.38(18)
6.4(4)
7.9(4)
3.42(18)
11.1(4)
34.3(13)
73(4)
354(3)
354(3)
76.4(18)
7
7
9
1
(reducing end)
(non-reducing end)
0
around the primary hydroxyl group on C-6 is 75.54° indicating a
gauche-trans conformation. The primary amide forms a discrete
hydrogen bond between one of the amide N–H groups and the het-
erocyclic oxygen of an adjacent glucopyranose ring, forming C(7)
chains along the b axis (Figs. 1 and 2), that is, hydrogen bonded
Single-crystal XRD analysis of crystals of compound 7 shows
that the form obtained was a methanol solvate. Cremer–Pople
parameters (Table 3) for the glucopyranose rings of both the reduc-
4
ing end and the non-reducing end were consistent with C
1
confor-
mations. The dihedral angle about the primary hydroxy group in

3
2
H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
Figure 1. View of crystal structure of compound 3 showing discrete hydrogen bond between primary amide N–H and pyranose oxygen forming C(7) chains.
that of methyl b-cellobioside methanol solvate which also crystal-
lised in the P2 space group. However, significant differences
1
OH
1
5
O
O
HO
HO
were observed in the interaction of the methanol molecule and in
intramolecular hydrogen bonding. Whereas in compound 7, the sol-
vated methanol is seen to hydrogen bond to the amide carbonyl, in
the structure of methyl b-cellobioside methanol solvate the meth-
anol molecule is hydrogen bonded to the primary hydroxyl of the
reducing glucopyranose. Also in the structure of methyl b-cellobio-
side methanol solvate, the 3-position hydroxyl of the reducing glu-
copyranose is participating in a hydrogen bonded ring involving the
non-reducing pyranose oxygen and primary hydroxyls, unlike the
hydrogen bonding motifs illustrated in Figure 8.
O
H
N
H
OH
OH
O
O
OH
OH
H
O
N
H
HO
OH
O
O
HO
HO
O
H
Also in the structure of 7ꢀMeOH, there is a short contact of 2.1 Å
N
H
OH
0
between H1 and H4. Both C–H bonds are axial and approximately
parallel. Compound 7 is a good subject for prediction of properties
Figure 2. Illustration of discrete hydrogen bond between primary amide N–H and
pyranose oxygen forming C(7) chains of compound 3 (depicted in red). (For
interpretation of the references to colour in this figure legend, the reader is referred
to the web version of this book.)
of a helix consisting of repetition of either of the glucopyranose
rings. The parallel C1 –H and C4–H bonds would correspond to a
0
twofold screw axis if present in an extended cellulose-like poly-
1
6
mer. Extrapolation of helix properties from crystal structure data
of small molecule glucopyranose derivatives has been developed
by French and Johnson as a technique for obtaining data on model
the non-reducing pyranose is ꢁ60.75° while that for the reducing
pyranose is ꢁ75.06°, equivalent to gauche–gauche conformations
in both cases. The angle at the oxygen joining the pyranose rings
is 115.3°. The amide N–H groups are donating hydrogen bonds to
1
7
cellulose chains. The necessary inputs for the extrapolation are
the virtual bond length of the glucopyranose residue, that is, the
O1–O4 distance, the virtual angle formed by two such rings and
the virtual torsion angle formed by three such rings. Using the
non-reducing glucopyranose of compound 7 as such a model and
the formulae given by French and Johnson gives the predicted
number of glucopyranose residues per turn of the model helix as
ꢁ2.19, indicating a left-handed helix which advances 5.19 Å per
glucopyranose residue. These values are within the ranges given
by French and Johnson based on calculations using data from 23
0
the 3-OH of one molecule and the 6 -OH of another, while the amide
carbonyl accepts a hydrogen bond from the methanol molecule
(Figs. 5 and 6). Intramolecular hydrogen bonds are observed be-
tween O3–H and the oxygen of the non-reducing pyranose, and
0
O2 –H and O6, giving rise to seven-membered and nine-membered
intramolecular hydrogen bonded motifs, designated as S(7) and
6
S(9) motifs respectively using Etter’s notation (Figs. 7 and 8).
A
0
17
similar S(9) motif involving an O6–Hꢀ ꢀ ꢀO2 bond was observed in
small molecules.
0
the structure of cyclohexyl 4 -O-cyclohexyl b-
D
-cellobioside cyclo-
1
4
hexane solvate. The O2–H of a separate molecule accepts a hydro-
gen bond from the O6 –H and donates a hydrogen bond to the O3
forming a hydrogen bonded ring, designated as a R (9) motif using
Etter’s notation, which also involves the O3-H. . .O intramolecular
2.3. Preparation of acetylated sulfide-amido, sulfoxide-amido
and sulfonyl-amido glucose derivates
0
3
3
6
In the crystal structures for compounds 3 and 7 discussed
above, the primary amide groups are involved in hydrogen bonding
with pyranose hydroxyls or oxygens rather than generating famil-
iar primary amide motifs such as ‘amide ladders’. This is not very
hydrogen bond (Figs. 7 and 8). In the structure, the molecules form
layers that cross each other as shown in Figure 9, rather than a her-
ringbone pattern. A comparable crystal structure for compound 7 is

H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
33
Figure 3. View of crystal structure of compound 3 showing C(17) chains resulting from amide N–H hydrogen bond donation (to pyranose oxygen) and amide oxygen
hydrogen bond acceptance (from primary hydroxyl) in compound 3.
of further oxidising these to the sulfoxide 10 and sulfone 11 was an
obvious extension of the system (Scheme 2).
OH
HO
OH
HO
OH
HO
HO
O
O
Amidosulfide 9 was obtained by reaction of glucose pentaace-
H
H
tate 8 with thiourea in the presence of BF
3
2
ꢀEt O, generating a thio-
O
OH
H
O
OH
H
O
OH
H
uronium intermediate in situ which was subsequently hydrolysed
and the resulting thiolate reacted with chloroacetamide. Careful
oxidation with OxoneÒ gave the sulfoxide 10, while oxidation of
9 with mCPBA gave the sulfone 11. Sulfoxide 10 appeared to be a
single diastereoisomer by NMR although the yield of isolated prod-
uct was very modest (33%) so that the formation of some quantity
of the epimeric sulfoxide which would have been removed during
purification cannot be ruled out.
O
H
O
H
O
H
H N
2
H N
2
O
O
O
O
O
N
N
N
O
O
O
OH
O
OH
HO
HO
HO
2.4. Crystal structures of acetylated sulfide-amido glucose
derivative 9 and sulfoxide-amido glucose derivate 10
HO
OH
OH
Figure 4. Illustration of C(17) chains resulting from amide N–H hydrogen bond
donation (to pyranose oxygen) and amide oxygen hydrogen bond acceptance (from
primary hydroxyl) in compound 3 (depicted in red). (For interpretation of the
references to colour in this figure legend, the reader is referred to the web version of
this book.)
Crystals of compounds 9 and 10 suitable for single-crystal X-ray
analysis were obtained by allowing undersaturated solutions of 9
and 10 in methanol to slowly evaporate at ambient temperature,
however suitable crystals of sulfone 11 were not obtained. Crystal-
lographic data for compounds 9 and 10 are given in Table 1.
1 1 1
Compound 9 crystallised in orthorhombic P2 2 2 space group.
4
surprising as the glucopyranose groups offer extensive hydrogen
bond donating and accepting capacity, although it might have been
hoped that a degree of molecular recognition may have existed be-
tween the amide groups. This could be moderated by blocking the
hydroxyls so as to reduce the hydrogen bond donating capacity of
the glucopyranoses. Such derivatives would be protected gluco-
sides and therefore would not display the full supramolecular
characteristics of sugars in the crystalline solid state. However,
informative supramolecular solid state chemistry would still be
obtained and it would be possible to evaluate whether typical
amide supramolecular motifs were possible with such systems un-
der any circumstances. The sulfide and sulfoxide linked peracety-
lated glucosyl primary amides 9 and 10 were synthesised for this
purpose. While the sulfide linkage in compound 9 was formed pri-
marily to bind the amide and peracetyl glucose regions, the option
Cremer–Pople parameters (Table 3) are consistent with a C con-
1
formation. The amide N–H groups donate hydrogen bonds to the
pyranose oxygen and the carbonyl group of the 2-acetoxy group
of adjacent molecules (Figs. 10 and 11).
Compound 10 crystallised as monoclinic P2 . Compound 10 has
1
4
Cremer–Pople parameters (Table 3) relating to typical C1 values.
The primary amide groups form C(4) hydrogen bonded chains. In
each amide group, the N–H not involved in the C(4) motif is donat-
ing a hydrogen bond to an amide carbonyl in a parallel chain form-
2
ing a series of R (8) rings, giving rise to a ladder-like motif referred
3
1
8
to as a 2 axis (Figs. 12 and 13), although not the more common
1
2
2
‘amide ladder’ composed of R (8) rings. The sulfur atom of the
sulfoxide group is a stereogenic centre having S configuration.
The packing observed in the structure of compound 10 would ap-
pear to maximise density as illustrated by Figure 14.

3
4
H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
Figure 5. View of the crystal structure of 7ꢀMeOH solvate showing hydrogen bonding interactions of the primary amide groups.
OH
OH
O
HO
HO
O
O
O
H
HO
O
N
H
OH
OH
OH
O
OH
O
O
HO
HO
O
O
O
H
HO
N
H
OH
OH
H
N
OH
OH
O
HO
HO
HO
O
H
O
O
OH
OH
H
Me
O
Figure 6. Illustration of the hydrogen bonding interactions of the primary amide groups in the structure of 7ꢀMeOH solvate.
2
.5. Conclusion
drive formation of crystal structures based on distinct amide and
sugar motifs, at least in the crystal forms obtained, while specific
supramolecular interactions between the primary amide groups
were observed in the acetylated sulfoxide 10. This suggests that
crystal engineering of sugars through exploitation of primary
amide motifs may be possible. However, modification of the hydro-
xy groups and/or inclusion of further functionality may be neces-
sary which would limit applications. Another possibility is that
further research on the nucleation and growth of compounds such
as 3 and 7 may generate new crystal forms with distinct amide and
sugar motifs. Alternatively, modification of the amide functional-
ity, for example, addition or removal of methylene groups, may
produce compounds with such crystal structures.
Primary amide derivatives of glucose and cellobiose, com-
pounds 3 and 7, have been prepared and their crystal structures
determined. These structures did not display common amide type
2
motifs such as C(4) chains and R2 (8) dimers, but rather motifs
involving both sugar and amide groups. For compound 3, a C(17)
chain with two molecules in the repeat unit was observed. For
compound 7, the amide N–H groups donated hydrogen bonds to
oxygen atoms on the cellobiose units, while intramolecular hydro-
gen bonds giving rise to S(7) and S(9) motifs were observed in
3
3
addition to a R (9) motif. Sulfide 9, in which the glucopyranose
hydroxyls were acetylated, displayed amide N–H groups donating
to glucopyranose oxygen and an acetyloxy group. However, sulfox-
2
ide 10 displays an interesting ladder-like motif composed from R
3. Experimental
3
(
1
8) rings. This motif, also known as a primary amide 2 axis motif,
is not as common as the amide ladder but has been observed in
crystal structure of some primary amides, for example adipamide
and 2-chlorobenzamide.
The structures studied generally display individual hydrogen
bonding patterns featuring motifs involving both primary amide
and sugar groups rather than distinct amide-based and sugar-
based motifs. In the case of the acetylated amidoglucosyl sulfoxide
3.1. General methods
1
8
All commercial reagents were purchased from Sigma–Aldrich
and were used without further purification. All solvents were
either of a HPLC grade or distilled prior to use. Column chromatog-
raphy was conducted using Merck silica gel 60, typically with a
30:1 ratio of silica to sample. Infrared spectra were recorded on a
1
1
0, a characteristic primary amide motif was observed. Hence for
Perkin–Elmer Paragon 1000 FT-IR spectrometer. The H NMR spec-
three of the compounds studied, the degree of molecular recogni-
tion between the primary amide groups was not strong enough to
tra were recorded on a Bruker AVANCE 300 MHz spectrometer.
Chemical shift values (d and d ) are expressed as parts per million
H C

H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
35
were recorded on a Waters LCT Premier LC–MS instrument in elec-
trospray ionisation (ESI) positive mode using 50% MeCN–H O con-
taining 0.1% HCO H as eluant; samples were made up in MeCN.
2
2
3
3
.2. Synthesis
.2.1. Methyl 1-O-(-2-carboxy)methyl-2,3,4,6-tetra-O-acetyl-b-
D
-
glucopyranose (2)
,3,4,6-Tetra-O-acetyl-1-O-trichloroacetimidoyl-
nose 1 (1.50 g, 3.05 mmol) was stirred in dry CH
2
a
-
D
-glucopyra-
Cl (30 mL)
along with methyl glycolate (0.26 mL, 3.36 mmol) over 4 Å mol
O (0.41 mL, 3.36 mmol) was added and
1
9
2
2
sieves at ꢁ25 °C. BF
3
ꢀEt
2
the solution was allowed to slowly warm to room temperature.
After 4–5 h, the solution was filtered and washed with satd aq.
NaHCO
3
soln (2 ꢂ 20 mL), H O (2 ꢂ 20 mL) and brine (20 mL).
2
The solvent was removed in vacuo and the resulting residue was
purified with column chromatography using EtOAc: hexane to
yield a white solid (0.95 g, 74%). IR (KBr);
m 2958 (CH), 1756
ꢁ1
(O–C–O); 1
(
C@O), 1371 (CH), 1235 (O–C@O) and 1045 cm
H
NMR (CDCl
3
): d 1.95 (3H, s, OAc), 1.96 (3H, s, OAc), 2.02 (3H, s,
3
OAc), 2.03 (3H, s, OAc), 3.63 (1H, ddd, J = 9.0, 4.8, 2.4 Hz, H-5),
.69 (3H, s, OCH
3
), 4.07 (1H, dd, J = 12.0, 3J = 2.4 Hz, H-6), 4.19
2
3
2
3
0
(
(
(
(
1H, dd, J = 12.0, J = 4.8 Hz, H-6 ), 4.23 (2H, s, OCH
1H, d, J = 7.8 Hz, H-1), 4.98 (1H, dd, J = 9.0, 7.8 Hz, H-2), 5.02
2
CO
2
Me), 4.60
3
3
Figure 7. View of the crystal structure of 7ꢀMeOH solvate showing intramolecular
3
3
13
1H, t, J = 9.0 Hz, H-4), 5.18 (1H, t, J = 9.0 Hz, H-3); C NMR
CDCl ): d 19.59 (CH ), 19.60 (CH ), 19.71 (CH ), 19.72 (CH ),
0.98 (OCH ), 60.77 (C-6), 63.94 (CH ), 67.29 (C-4), 69.92 (C-2),
0.93 (C-5), 71.50 (C-3), 99.11 (C-1), 168.42, 168.60, 168.66,
Me).
3
3
S(7) and S(9), and intermolecular R (9) hydrogen bonding motifs.
3
3
3
3
3
5
7
3
2
OH
OH S(7)
169.18, 169.65 (4 ꢂ OAc, 1 ꢂ CO
2
O
HO
HO
O
O
O
H
O
O
O
NH2
3.2.2. 1-O-(2-Carboxamido)methyl-b-D-glucopyranose (3)
H
Methyl 1-O-(-2-carboxy)methyl-2,3,4,6-tetra-O-acetyl-b-
D-glu-
OH
H
R33(9)
copyranose 2 (1.00 g, 2.39 mmol) was stirred in 2 M NH in MeOH
3
O
OH
soln (20 mL, 40 mmol) for 1 h. The methanolic ammonia was re-
moved under reduced pressure and the crude residue was recrys-
tallised from a minimum of hot MeOH to yield a white solid
O
H
NH
2
O
HO
HO
O
O
O
O
S(9)
O
H
OH
(0.55 g, 99%). Mp 165.49 °C; IR (KBr); m 3422 (OH, NH), 2923
(
1
3
CH), 1672 (NHC@O), 1379 (CH), 1325 (CH), 1222 (O–C@O) and
Figure 8. Intramolecular S(7) (depicted in blue), S(9) (depicted in green), and
ꢁ1
1
132 cm
(C–O–C); H NMR (DMSO-d
6
): d 3.41–3.48 (1H, m),
3
intermolecular R (9) (depicted in red), hydrogen bonding motifs in the structure of
3
3
2
.67 (1H, ddd, J = 9.9, 6.3, 1.8 Hz), 3.89 (1H, d, J = 15.0 Hz, OCH2-
7
ꢀMeOH solvate. (For interpretation of the references to colour in this figure legend,
2
the reader is referred to the web version of this book.)
CO
2
Me), 4.09 (1H, d, J = 15.0 Hz, OCH
2
CO
2
Me), 4.16 (1H, d,
3
3
3
J = 9.0 Hz, H-1), 4.55 (1H, t, J = 6.0 Hz), 4.95 (1H, d, J = 6.0 Hz),
.02 (1H, d, J = 3.0 Hz), 5.51 (1H, d, J = 3.0 Hz), 7.42 (2H, br s,
3
3
5
1
3
(
ppm). Elemental analyses were performed by the Microanalysis
2 6 2 2
NH ); C NMR (DMSO-d ): d 60.90 (CH ), 47.81 (CH ), 69.88
Laboratory, University College Cork, using an Exeter Analytical
CE440 elemental analyser. High resolution mass spectra (HRMS)
(CH), 73.35 (CH), 76.16 (CH), 76.98 (CH), 103.02 (C-1), 171.57
(CONH2).
Figure 9. Cross layering of cellobioside moieties of 7ꢀMeOH viewed along the crystallographic b axis.

3
6
H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
OAc
OAc
OAc
a
O
S
O
O
b
O
AcO
AcO
AcO
AcO
OAc
S
CONH2
AcO
AcO
CONH
2
AcO
AcO
AcO
8
9
10
c
OAc
O
O O
S
AcO
AcO
CONH2
AcO
1
1
Ò
Scheme 2. Reagents and conditions: (a) NH
0 min.
2
CSNH
2
, BF
3
ꢀEt
2 2 2 3 2 3
O, MeCN, D, 4 h, then ClCH CONH , Et N, rt, 1 h; (b) Oxone , MeCN, H O, rt, 12 h; (c) mCPBA, CHCl , 0 °C, rt,
3
solution was stirred at ambient temperature for 12 h. The solvent
was removed in vacuo and the resulting syrup was dissolved in
3
CHCl (150 mL). The organic phase was washed with 1 M HCl
(
2 ꢂ 30 mL), H
2
O (2 ꢂ 30 mL) and brine (30 mL), dried over MgSO
4
and the solvent removed under reduced pressure. The crude solid
was subjected to column chromatography with ethyl acetate/hex-
ane (1:1) as eluant, to yield
ra-O-acetyl-b- -glucopyranosyl)-2,3,6-triacetate as a white solid
1.21 g, 64% yield) as a 3.2:1 mix of anomers ( :b) (by NMR integra-
anomer) d: 1.93 (3H, s), 1.96 (3H, s), 1.98
3H, s), 2.02 (3H, s), 2.04 (3H, s), 2.08 (3H, s), 2.09 (3H, s), 3.64–
ab-D-glucopyranose-4-O-(2,3,4,6-tet-
D
(
a
1
3
tion) H NMR (CDCl , a
(
3
3
3
4
.61 (1H, m), 3.71 (1H, t, J = 9.2 Hz), 3.82–3.96 (2H, m), 4.14–
3
.98 (1H, m), 4.30 (1H, dt, J = 6.7, 3.9 Hz), 4.51–4.45 (2H, m),
.79–4.69 (1H, m), 4.88 (1H, ddd, J = 9.0, 6.0, 3.0 Hz), 5.16–4.99
3
3
3
13
(
d
(
(
2H, m), 5.31 (1H, t, J = 4.3 Hz), 5.45 (1H, t, J = 9.0 Hz). C NMR
(CDCl ), 20.74 (2 ꢂ CH ), 20.85 (CH ), 20.94
): 20.64 (2 ꢂ CH
2 ꢂ CH ), 61.77 (CH ), 62.00 (CH ), 68.00 (CH), 68.29 (CH), 69.55
CH), 71.52 (CH), 71.83 (CH), 72.06 (CH), 72.22 (CH), 73.11 (CH),
C
3
3
3
3
3
2
2
7
1
1
3.19 (CH), 73.42 (CH), 90.15 (CH), 95.35 (C-1, unknown anomer),
00.96 (C-1, unknown anomer), 100.97 (CH), 169.30 (OAc),
69.56 (OAc), 169.96 (OAc), 170.53 (OAc), 170.64 (OAc), 170.84
(
OAc), 170.92 (OAc). The
a
b-
-glucopyranosyl)-2,3,6-triacetate obtained (5.0 g,
CCN (1.57 mL, 15.72 mmol) were stirred in dry
2
(80 mL) at 0 °C for 30 min. DBU (0.12 mL, 0.78 mmol) was
D-glucopyranose-4-O-(2,3,4,6-tetra-
O-acetyl-b-
7
CH Cl
D
.86 mmol) and Cl
3
2
added dropwise and the solution was allowed to warm to room
temperature and stirred for 12 h. The solvent was removed in vacuo
Figure 10. View of the crystal structure of compound 9 showing hydrogen bonding
interactions of the primary amide group.
and the residue was subjected to silica gel chromatography (40:60
1
EtOAc/hexane) to yield a foam (3.18 g, 52%); H NMR (CDCl
3
): d 1.99
H
N
AcO
(3H, s, OAc), 2.01 (3H, s, OAc), 2.02 (3H, OAc), 2.03 (3H, s, OAc), 2.04
(3H, s, OAc), 2.09 (3H, s, OAc), 2.10 (3H, s, OAc), 3.66 (1H, ddd,
J = 9.0, 6.0, 3.0 Hz, H-5 ), 3.84 (1H, t, J = 9.0 Hz, H-4), 4.02–4.15
AcO
AcO
S
H
OAc
O
3
0
3
O
O
O
O
3
0
AcO
AcO
OAc
AcO
S
H
(3H, m, H-5, H-6), 4.39 (1H, dd, J = 12.0, 3.0 Hz, H-6 ), 4.49–4.56
N
H
3
(
2H, m), 4.94 (1H, t, J = 9.0 Hz), 5.04–5.15 (3H, m, H-2), 5.53 (1H,
t, J = 9.0 Hz, H-3), 6.48 (1H, d, J = 3.9 Hz, H-1), 8.66 (1H, s, NH);
O
3
3
H
N
1
3
Me
C NMR (CDCl
3
): d 20.49 (CH
3
), 20.57 (CH
3
), 20.63 (2 ꢂ CH
3
),
AcO
AcO
S
H
0
2
6
0.70 (2 ꢂ CH ), 20.84 (CH
3
3
), 61.38 (C-6), 61.55 (C-6 ), 67.70 (CH),
9.29 (CH), 69.86 (CH), 70.96 (CH), 71.67 (CH), 72.02 (CH), 73.06
O
O
OAc
(
CH), 76.12 (CH), 92.86 (C-1), 100.98 (C-1), 160.98 (Cq), 169.09
Figure 11. Illustration of hydrogen bonding interactions of the primary amide
group in the structure of compound 9.
(OAc), 169.29 (OAc), 169.46 (OAc), 170.06 (OAc), 170.17 (OAc),
1
70.28 (OAc), 170.50 (OAc).
0
0
0
0
3
.2.4. Methyl 1-O-(2-carboxymethyl)-2,2 ,3,3 ,4 ,6,6 -hepta-O-
-cellobiose (6)
-Glucopyranose-4-O-(2,3,4,6-tetra-O-acetyl-b-
osyl)-2,3,6-triacetyl-1-O-trichloroacetimidate 5 (2.0 g, 2.56 mmol)
and methyl glycolate (0.22 mL, 2.82 mmol) were stirred in dry CH Cl
(60 mL) over 4 Å mol sieves at ꢁ25 °C. BF ꢀEt O (0.35 mL, 2.82 mmol)
3
.2.3. Preparation of
acetyl-b- -glucopyranosyl)-2,3,6-triacetyl-1-O-
trichloroacetimidate (5)
To a solution of b- -glucopyranose-4-O-(2,3,4,6-tetra-O-acetyl-
-glucopyranosyl)-1,2,3,6-tetraacetate (4) (2.0 g, 2.94 mmol) in
a
-
D
-glucopyranose-4-O-(2,3,4,6-tetra-O-
acetyl-b-D
D
a-D
D-glucopyran-
D
2
2
b-
D
3
2
20
THF was added benzylamine
(0.35 mL, 3.24 mmol) and the
was added and the solution was allowed to warm slowly to room

H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
37
Figure 12. View of the crystal structure of compound 10 showing hydrogen bonding interactions of the primary amide group.
AcO
OAc
AcO
OAc
AcO
OAc
temperature. After 4–5 h, the solution was filtered and washed with
satd aq NaHCO O (2 ꢂ 20 mL) and brine
soln (2 ꢂ 20 mL), H
20 mL). The solvent was removed in vacuo the resulting residue
was purified with column chromatography using EtOAc: hexane to
yield a white solid (1.21 g, 67%). IR (KBr); 2958 (CH), 1756 (C@O),
OAc
OAc
O
3
2
A
c
(
AcO
H
O
AcO
H
O
AcO
H
O
m
S
O
O
S
O
O
S O
O
ꢁ
1
1
1
3
371 (CH), 1235 (O–C@O) and 1045 cm (O–C–O); H NMR (CDCl ):
d 1.98 (3H, s, OAc), 2.01 (3H, s, OAc), 2.03 (6H, s, 2 ꢂ OAc), 2.08 (3H, s,
3
N
H
N
H
N
OAc), 2.09 (3H, s, OAc), 2.12 (3H, s, OAc), 3.59 (1H, ddd, J = 6.0, 3.0,
0
3
R23(8)
R2
1
OCH
.5 Hz, H-5 ), 3.65 (1H, ddd, J = 6.0, 3.0, 1.5 Hz, H-5), 3.74 (3H, s,
3
(8)
H
3
3
), 3.80 (1H, t, J = 9.0 Hz), 4.00–4.10 (2H, m), 4.25 (2H, s, OCH2-
CO Me), 4.36 (1H, dd, J = 9.0, 3.0 Hz), 4.50–4.54 (2H, m), 4.69 (1H,
H
N
R23(8)
H
N
3
2
3
3
d, J = 7.8 Hz, H-1), 4.93–4.89 (2H, m), 5.06 (1H, t, J = 9.1 Hz), 5.14
H
O
O
H
O
O
3
3
13
(
1H, t, J = 9.0 Hz), 5.21 (1H, t, J = 9.0 Hz); C NMR (CDCl
), 20.67 (CH ), 20.73 (CH ), 20.85 (CH ), 51.98 (OCH
CO Me), 67.77 (CH), 71.19 (CH),
3
): d 20.55
S
S
(
6
4 ꢂ CH
3
3
0
3
3
3
),
1.54 (C-6), 61.64 (C-6 ), 65.10 (CH
2
2
AcO
O
AcO
O
7
1.60 (CH), 71.93 (CH), 72.12 (CH), 72.83 (CH), 72.92 (CH), 76.29
0
(
CH), 100.00 (C-1), 100.74 (C-1 ), 169.01, 169.30, 169.51, 169.71,
OAc
OAc
1
69.86, 170.23, 170.28, 170.50 (7 ꢂ OAc, 1 ꢂ CO
2
Me).
OAc
AcO
OAc
AcO
3
.2.5. 1-O-(2-Carboxamido)methyl-4-O-(b-
D
-glucopyranosyl)-b-
Figure 13. Illustration of hydrogen bonding interactions of the primary amide
group in the structure of compound 10 forming R3 (8) hydrogen bond patterns
D
-glucopyranose (7)
2
0
0
0
Methyl 1-O-(2-carboxymethyl) 2,2 ,3,3 ,4,6,6 -hepta-O-acetyl-b-
(
depicted in red). (For interpretation of the references to colour in this figure legend,
D
3
-cellobiose 6 (1.5 g, 2.12 mmol) was stirred in a 2 M NH in MeOH
the reader is referred to the web version of this book.)

3
8
H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
Figure 14. Packing of molecules of compound 10.
soln (30 mL, 60 mmol) for 1 h. The methanolic ammonia was re-
moved under reduced pressure and the crude residue was recrys-
tallised from a minimum of hot MeOH to yield a white solid
thiourea (1.91 g, 50.24 mmol). The solution was heated to reflux
for 4 h. On cooling to room temperature, 2-chloroacetamide
(2.34 g, 27.5 mmol) was added followed by Et
tion was stirred for 1 h and the solvent removed in vacuo, the
resulting syrup was dissolved in CHCl (150 mL) and washed with
) and the solvent
3
N (10 mL). The solu-
(
(
(
0.81 g, 97%). Mp 135.5 °C; IR (KBr):
m
3414 (OH and NH
CH), 1675 (CO) and 1077 cm (C–O–C); 1H NMR (D
O): d 3.32
1H, t, J = 9.0 Hz), 3.38–3.54 (4H, m), 3.58–3.68 (3H, m), 3.74 (1H,
2
), 2917
ꢁ1
2
3
H
2
O (2 ꢂ 50 mL), brine (1 ꢂ 50 mL), dried (MgSO
4
3
3
dd, J = 12.3, 5.7 Hz), 3.83 (1H, dd, J = 12.3, 4.8 Hz), 3.92 (1H, dd,
removed under reduced pressure. The resulting foam was recrys-
tallised from hot MeOH to yield a pale yellow solid (5.1 g, 48%).
3
J = 12.3, 1.8 Hz), 3.98 (1H, dd, 3J = 12.0, 1.8 Hz), 4.27 (1H, d,
3
Me), 4.39 (1H, d, 3J = 15.9 Hz, OCH
J = 15.9 Hz, OCH
.52 (1H, d, J = 7.8 Hz, H-1), 4.55 (1H, d, J = 7.8 Hz, H-1 );
2
CO
2
2
CO
2
Me),
Mp 160.47 °C; IR (KBr)
m 3387 (NH), 2943 (CH), 1734 (C@O),
3
3
0
13
4
C
1644 (NHC@O), 1379 (CH), 1232 (O–C@O), 1031 (O–C–O) and
ꢁ
1 1
NMR (D
2.73 (CH), 73.15 (CH), 74.11 (CH), 74.87 (CH), 75.50 (CH), 75.99
CH), 78.43 (CH), 102.24 (C-1), 102.57 (C-1), 175.04 (CONH );
2 2
O): d 59.86 (CH ), 60.58 (CH
2
), 67.77 (OCH
2
), 69.46 (CH),
916 cm
3
; H NMR (CDCl ) d 1.95 (3H, s, OAc), 1.97 (3H, s, OAc),
2
7
2.00 (3H, s, OAc), 2.03 (3H, s, OAc), 3.16 (1H, d, J = 15.0 Hz,
2
(
2
SCH
2
CONH
2
), 3.40 (1H, d, J = 15.0 Hz, SCH
2
CONH
2
), 3.69 (1H, dt,
+
3
3
0
calcd. C14
H
25NO12Na, 422.1275; found 422.1249 [M+Na ].
J = 9.3, 3.9 Hz, H-5), 4.12 (2H, d, J = 3.9 Hz, H-6+6 ), 4.53 (1H, d,
J = 9.3 Hz, H-1), 4.98 (1H, t, J = 9.3 Hz, H-2), 5.01 (1H, t,
J = 9.3 Hz, H-4), 5.17 (1H, t, J = 9.3 Hz, H-3), 5.75 (1H, br s, NH),
6.60 (1H, br s, NH ); C NMR (CDCl
20.62 (CH ), 20.70 (CH ), 33.78 (CH
69.60 (C-2), 73.48 (C-3), 76.21 (C-5), 83.71 (C-1), 169.36 (CONH
3
3
3
3
3
.2.6. 1-S-(-2-Carboxamido)methyl-1-deoxy-1-thio-2,3,4,6-
tetra-O-acetyl-b- -glucopyranose (9)
To a solution of b- -glucose pentaacetate 8 (9.8 g, 25.12 mmol)
in MeCN was added BF O (3.08 mL, 37.5 mmol) followed by
ꢀEt
0
13
D
3
): d 20.15 (CH
3
), 20.54 (CH
3
),
D
3
3
2
), 61.66 (C-6), 68.07 (C-4),
3
2
2
),

H. A. Moynihan et al. / Carbohydrate Research 374 (2013) 29–39
39
1
69.41 (OAc), 170.04 (OAc), 170.60 (OAc), 171.26 (OAc); Anal Calcd
for C16 21NO10S: C, 45.82; H, 5.05; N, 3.34. Found: C, 45.45; H, 5.50,
N, 3.21.
X2S was used for 3 and 9, as previously described.21 A Rigaku FR-E+
diffractometer fitted with VariMax HF optics to give monochroma-
H
tised Mo K
a radiation was used for 10 following previously de-
2
2
scribed procedures. Crystals suitable for analysis were obtained
by recrystallisation from ethanol or methanol by slow evaporation.
Calculations for 3, 7 and 9 were made using the APEX2 v2009.3-0
3
.2.7. 1-S-(-2-Carboxamido)methyl-1-deoxy-1-sulfinyl-2,3,4,6-
tetra-O-acetyl-b- -glucopyranose (10)
Oxone (1.46 g, 4.77 mmol) was added to a solution of 1-S-(-2-
carboxamido)methyl-1-deoxy-1-thio-2,3,4,6-tetra-O-acetyl-b-
glucopyranose 9 (2.0 g, 4.77 mmol) in a 1:1 mixture of MeCN:H
50 mL) and the mixture was stirred for 12 h. The solution was fil-
tered and the solvent removed in vacuo. The syrup was dissolved
in CHCl (100 mL) and the organic phase was washed with H
) and the solvent removed
D
Ò
23
software incorporating the SHELX suite of programs for structure
2
4
D-
solution and refinement. Calculations for 10 were made using
CrystalClear-SM Expert 2.0 r13 software. The structure was
solved by Superflip and refined using SHELX-97. All diagrams
were prepared using Mercury 3.0. The small crystal size of 7
and the relatively large number of unobserved data (47%) contrib-
ute to the high Rint value.
2
5
2
O
2
6
24
(
2
7
3
2
O
(
2 ꢂ 20 mL), brine (20 mL), dried (MgSO
4
under reduced pressure. The resulting foam was purified by col-
umn chromatography using EtOAc (100%) as eluant to yield a white
Acknowledgments
solid (0.15 g, 33%) Mp 194.2 °C; IR (KBr)
m
3387 (NH), 2943 (CH),
1
1
735 (C@O), 1644 (NHC@O), 1379 (CH), 1232 (O–C@O) and
This publication has emanated from research conducted with
the financial support of the Science Foundation Ireland under
Grant Numbers 07/SRC/B1158 and 05/PICA/B802/EC07.
ꢁ
1
(C–O–C); 1H NMR (CDCl
) d 2.00 (3H, s, OAc), 2.06
3
031 cm
2
(
6H, s, 2 ꢂ OAc), 2.08 (3H, s, OAc), 3.64 (1H, d, J = 15.0 Hz, S(O)CH2-
2
2 2 2
CONH ), 3.87 (1H, d, J = 15.0 Hz, S(O)CH CONH ), 4.11–4.26 (3H,
0
3
m, H-6+6 , H-5), 5.04 (1H, d, J = 9.3 Hz, H-1), 5.05 (1H, t,
References
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3
3
J = 9.3 Hz, H-4), 5.28 (1H, t, J = 9.3 Hz, H-2), 5.47 (1H, t,
0
13
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ꢁ1
1
(
O–C@O), 1222 (C–O–C), 1325 (SO
2
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1
OAc), 2.02 (3H, s, OAc), 3.97 (1H, d, J = 15.0 Hz, SO
2
CH
), 3.98–4.08 (2H, m, H-6),
.21–4.30 (1H, m, H-5), 4.96 (1H, t, J = 4.8 Hz, H-4), 5.23 (1H, d,
2 2
CONH ),
2
4
4
2 2 2
.20 (1H, d, J = 15.0 Hz, SO CH CONH
1
3
3
3
J = 9.0 Hz, H-1), 5.39 (1H, t, J = 9.0 Hz, H-2), 5.48 (1H, t,
3
0
13
J = 9.0 Hz, H-3), 7.49 (1H, br s, NH), 7.68 (1H, br s, NH );
NMR d 20.18 (CH ), 20.24 (CH ), 20.33 (CH ), 20.47 (CH ), 55.10
SO CH CONH ), 61.34 (C-6), 65.68 (C-4), 67.21 (C-2), 72.70 (C-
), 74.88 (C-5), 85.75 (C-1), 162.37 (CONH ), 168.53 (OAc),
69.20 (OAc), 169.47 (OAc), 170.03 (OAc). MS-ESI: Found: m/z,
C
3
3
3
3
(
2
2
2
2
2
2
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3
1
4
2
+
76.0832; calcd for C16H23NO12SNa [M+Na ], 476.0839.
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.3. Solid state characterisation
2008, 41, 466–470.
Single-crystal X-ray diffraction measurements for 7 were col-
lected on a Bruker APEX II DUO diffractometer and a Bruker SMART