Studies on the synthesis of ether-, substituted alkyl-, or aryl-linked C-disaccharide derivatives

Article abstract of DOI:10.1016/j.carres.2011.02.009

A series of ether-, substituted alkyl-, or aryl-linked disaccharide derivatives have been synthesized in relatively good yield and characterized using different spectral techniques including single-crystal X-ray diffraction (XRD). β-Anomeric forms of sugar moiety in these derivatives were identified from ¹H NMR studies. The existence of inter- and intramolecular hydrogen bonding interactions were identified from single-crystal XRD studies.

Full text of DOI:10.1016/j.carres.2011.02.009

Carbohydrate Research 346 (2011) 722–727
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Studies on the synthesis of ether-, substituted alkyl-, or aryl-linked
C-disaccharide derivatives
⇑
Subbiah Nagarajan, M. Jeganathan Shanmugam, Thangamuthu Mohan Das
Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai 600 025, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of ether-, substituted alkyl-, or aryl-linked disaccharide derivatives have been synthesized in
relatively good yield and characterized using different spectral techniques including single-crystal
X-ray diffraction (XRD). b-Anomeric forms of sugar moiety in these derivatives were identified from 1H
NMR studies. The existence of inter- and intramolecular hydrogen bonding interactions were identified
from single-crystal XRD studies.
Received 22 November 2010
Received in revised form 2 February 2011
Accepted 7 February 2011
Available online 12 February 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Keywords:
Aromatic dialdehydes
C-b-Glycosides
Aldol condensation
Michael addition
b Anomer
Single-crystal X-ray diffraction
1. Introduction
research in the area of saccharide chemistry,17–20 we report herein
the facile synthesis of ether-, substituted alkyl-, or aryl-linked C-
The development of supramolecular chemistry and nanotech-
nology has relied mostly on the design of effective chemical tools
with a view to connecting them to construct more complex and
extensively developed superstructures. The ability to connect them
at well-defined distances leads to the development of useful de-
vices.1,2 Several stimuli-responsive supramolecular materials have
photo, chemical, electrical and mechanical properties, which offer
potential application in various fields, such as surface science, sep-
aration science, and bioapplications.3,4 An alteration in the
strength of the intermolecular non-covalent bonds via hydrogen
bonding, van der Waals forces, and coordinate bonding can result
in dramatic modification of the materials. Thus, the ability to pre-
pare an ethylene glycolate (EG) bearing two functional groups at
the ends of the chain is a major current challenge for most organic
chemists and is also a growing demand of the scientific commu-
nity.5–7 Poly(ethylene oxide) can form coordinate bonds with me-
tal ions and acts as an ion-transporting matrix.8–12 Several
ethylene glycol derivatives are used in the studies of neurodegen-
erative disorders, injuries of the central nervous system (CNS) and
also for the construction of a large number of engineering bioma-
terials, etc.13–16 In order to study the weak interactions that exist
in carbohydrates, it becomes increasingly important to understand
the nature of the packing forces. In a continuation of our on-going
disaccharide derivatives and the steric factors involved in the aldol
condensation of these 1-C-b- -glycosylic ketones with various
ether linked dialdehydes. The existence of inter- and intramolecu-
lar hydrogen bonding interactions has also been studied using
single-crystal XRD studies.
D
2. Results and discussion
2.1. Synthesis of C-b-D-glycosylic ketones
4,6-O-Butylidene-
glucopyranose were synthesized from
literature procedures.21–23 1-C-b-
-Glycosylic ketones, such as,
1-C-(4,6-O-butylidene-b- -glucopyranosyl)- (1a), 1-C-(4,6-O-ben-
zylidene-b- -glucopyranosyl)- (1b), 1-C-(2,3,4,6-tetra-O-acetyl-
b- -glucopyranosyl)- (1c), 1-C-(2,3,4-tri-O-acetyl-b- -xylopyrano-
syl)- (1d), and 1-C-(b- -galactopyranosyl-(1?4)- b- -glucopy-
ranosyl)propane-2-one (1e) were synthesized by Knoevenagel
condensation of 2,4-pentadienone with mono- ( -glucose, -xylose),
di- (lactose) and partially protected (4,6-O-butylidene- -glucopyr-
anose, 4,6-O-benzylidene- -glucopyranose) saccharide derivatives
D
-glucopyranose and 4,6-O-benzylidene-
D-
D-glucose by adopting
D
D
D
D
D
D
D
D
D
D
D
(Table 1).24–26 Although the synthesis of 1-C-b-
D-glycosylic ketones
are described in the literature,24–26 in the present report we have
extended the methodology to partially protected sugar derivatives
such as 1-C-(4,6-O-butylidene-b-D-glucopyranosyl)propane-2-one
(1a)17–20 and 1-C-(4,6-O-benzylidene-b-
2-one (1b).
D-glucopyranosyl)propane-
⇑
Corresponding author. Tel.: +91 44 22202814; fax: +91 44 22352494.
E-mail address: tmdas_72@yahoo.com (T. Mohan Das).
0008-6215/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2011.02.009

S. Nagarajan et al. / Carbohydrate Research 346 (2011) 722–727
723
Table 1
Synthesis of ether-linked disaccharide derivatives 3(a–d)
O
O
O
O
O
O
CH3
Pyrrolidine
O
O
+
R
Solvent
O
OHC
CHO
R
R
1(a-d)
O
O
2c
3(a-d)
3
Entry
1
R (1/3)
1(a–d) (mg)
Time (h)
10
d(H-1), JH1,H2
Solvent
CH2Cl2
Yield of 3(a–d) in mg (%)
H3C
H
O
O
O
548
616
3.80–3.94 (dd), 9.9 Hz
806 (92)
HO
OH
a
O
H
2
12
2.51–4.09 (m), —a
CH2Cl2
723 (77)
O
O
HO
OH
b
OAc
O
AcO
AcO
3
4
776
632
8
4.23–4.29 (dd), 12.3 Hz
3.68–4.07 (m), —a
CH2Cl2
CH2Cl2
824 (75)
640 (67)
OAc
c
O
AcO
AcO
18
OAc
d
a
Anomeric proton merged with other sugar skeletal protons.
Single crystals suitable for XRD analysis were obtained upon
slow evaporation of a solution of the 1-C-(2,3,4-tri-O-acetyl-b-
xylopyranosyl)propane-2-one (1d) and 1-C-(b- -galactopyrano-
syl-(1?4)- b- -glucopyranosyl)propane-2-one (1e) in CHCl3 and
bonding data for compound 1e are given in Table S2. The existence
of a b-anomeric form of sugar moiety in 1d and 1e is identified
from the corresponding torsion angles [1d: H(9)–C(9)–C(10)–
H(10) = 175.41° and 1e: H(1)–C(1)–C(2)–H(2) = 174.61°].
D
-
D
D
H2O, respectively. In our previous paper we reported the crystal
structures of various partially protected sugar derivatives.18 Now,
we have performed the single-crystal X-ray structural analysis of
2.2. Synthesis of triethylene glycol (TEG) dialdehydes
two different 1-C-b-
D
-glycosidic ketones and discussed their
TEG-ditosylate was synthesized by tosylation of TEG with p-
TsCl, using THF–water as solvent and NaOH as base.27–29 Various
dialdehydes linked via an ether chain 2(a–c) were synthesized by
the reaction of TEG-ditosylate with various hydroxyl-substituted
aromatic aldehydes such as 2-hydroxybenzaldehyde, 2-hydrox-
ynaphthaldehyde and 4-hydroxybenzaldehyde in the presence of
K2CO3 as base and DMF as solvent (Scheme 1).10 Three different
ether-based dialdehydes were synthesized and characterized using
1H and 13C NMR spectral studies. Single crystals suitable for XRD
analysis were obtained upon slow evaporation of the solution of
compound, 2b in ethyl acetate. An ORTEP view of compound 2b
is shown in Figure S6. Detailed crystallographic parameters of
compound, 2b are given in Table S3 (for Fig. S6 and Table S3, see
Supplementary data).
hydrogen-bonding interactions. The configuration and conforma-
tion of saccharide derivatives (1d and 1e) were established on
the basis of single-crystal XRD analysis. Detailed crystallographic
parameters of 1d and 1e are given in Table S1 (for Figs. S1–S5, Ta-
bles S1 and S2, see Supplementary data). The ORTEP and molecular
packing view of two different b-C-glycosidic ketones such as, 1-C-
(2,3,4-tri-O-acetyl-b-
(b- -galactopyranosyl-(1?4)- b-
(1e) are shown in Figures S1–S5.
D
-xylopyranosyl)propane-2-one (1d) and 1-C-
D
D-glucopyranosyl)propane-2-one
The self assembly of sugar derivatives was controlled by free
hydroxyl groups. In molecule 1d, all the free hydroxyl groups were
acetylated, and there is no inter- and intramolecular hydrogen
bonding. Whereas, in case of 1e free hydroxyl groups were not pro-
tected and there are strong hydrogen-bonding interactions be-
tween the molecules (Fig. S4). In the crystal lattice, each
molecule 1e is surrounded by four other molecules and four water
molecules interacting through hydrogen bonds, which resulted in
the formation of three-dimensional networks that resemble a
channel-type structure as shown in Figure S5. Detailed hydrogen
2.3. Synthesis of sugar-based triethylene glycolate derivatives
3(a–d)
Recently Little et al. reported the biological applications of
supramolecular ethylene glycol-linked saccharide derivatives and

724
S. Nagarajan et al. / Carbohydrate Research 346 (2011) 722–727
expected for a b-D-configured glucopyranose moiety. Structures
of sugar parts, reaction conditions, and yields are given in Table 1.
K2CO3, DMF
100 ºC, 14 h
O
R
3
Ts
O
+
R-OH
CHO
R
O
O
Ts
3
2a-c
2c
2.4. Synthesis of substituted aryl- or alkyl-linked disaccharide
derivatives 5(a–d)
CHO
OHC
R =
The reaction of 2-bromo-3-pyridinecarboxaldehyde (4a) and
3,4,5-trimethoxybenzaldehyde (4b) with 1-C-(4,6-O-butylidene-
2a
2b
b- -glucopyranosyl)propane-2-one (1a) was carried out at 50 °C
D
Scheme 1. Synthesis of TEG-dialdehydes.
in the presence of 1:1 MeOH–CH2Cl2 as solvent and pyrrolidine
(25 mol %) as the organic catalyst (Table 2). In the first step the al-
dol condensation of C-b-glycosidic ketone (1a) with aromatic or
heteroaromatic aldehydes led to the formation of
rated-C-b-glycosidic ketones. The resulting -,b-unsaturated-C-b-
glycosidic ketones underwent a Michael addition reaction with
another molecule of 1-C-(4,6-O-butylidene-b- -glucopyranosyl)
propane-2-one (1a) to give the substituted alkyl ketone-linked
disaccharide derivatives (5a and 5b). In this case, the control of sol-
vent ratio and equivalents of 1-C-b-D-glycosylic ketones determine
the nature of the product formation. Aldol condensation of
aromatic dialdehydes [isophthalaldehyde (4c) and thiophene-2,3-
dicarbaldehyde (4d)] with 1-C-(4,6-O-butylidene-b-D-glucopyran-
a-,b-unsatu-
also the challenges that remain in the synthesis of several of such
analogs.16 In the present studies, aldol condensation of O-TEG-
a
dialdehyde (2a and 2b) with 1-C-(4,6-O-butylidene-b-D-glucopyr-
D
anosyl)propane-2-one (1a) in the presence of various bases did
not lead to the formation of the ether-linked disaccharide deriva-
tive. This may be due to the presence of an ether chain at the
o-position to the aldehyde group, which induces the steric
hindrance. While by changing the position of ether linkage from
the o- to the p-position of TEG-dialdehyde leads to a significant
enhancement of reactivity towards 1-C-b-D-glycosylic ketones
1(a–d). Hence ether-linked disaccharide derivatives, 3(a–d) were
synthesized by the aldol condensation of TEG-dialdehyde 2c with
osyl)propane-2-one (1a) at ambient temperature in the presence
of CH2Cl2 as solvent and pyrrolidine (25 mol %) as organic catalyst
gives the corresponding disaccharide derivatives 5c and 5d,
respectively (Table 2).
various 1-C-b-D-glycosylic ketones, 1(a–d). In order to understand
the scope of the reaction, various protected and partially protected
saccharides were used in the present work. The formation of ether-
linked disaccharide derivatives 3(a–d) was identified from the 1H
and 13C NMR studies. 1H NMR spectrum of 3a notably exhibited
3. Conclusions
a large coupling constant for H-10 signal (d 3.90–3.94; JH1 ,H2
=
In conclusion, eight different ether- substituted, aryl-, or
alkyl-linked C-disaccharide derivatives were synthesized in one
0
0
9.9 Hz), indicating a trans-diaxial orientation of H-10, and H-20 as
Table 2
Synthesis of substituted aryl- or alkyl-linked disaccharide derivatives 5(a–d)
H
H
O
O
C3H7
Pyrrolidine
(25 mol %),
Solvent
C3H7
O
O
O
HO
O
O
O
CH3
OH
O
HO
(R)
HO
R-CHO
OH
OH
O
O
C3H7
O
H
5(a-d)
1a
3
Entry
1
R group 5(a–d)
4(a–d) (mg)
Time (h)
d(H-1), JH1,H2
Yield of 5(a–d) in mg (%)
Br
N
186
48
36
4.03 (d), 8.7 Hz
3.98 (t), 10.2 Hz
523 (73)
a
OCH3
OCH3
2
196
472 (65)
OCH3
b
3
4
134
140
12
16
3.94–3.97 (m), —a
4.04 (d), 7.5 Hz
569 (88)
509 (78)
c
S
d
a
Anomeric proton merged with other sugar skeletal protons.

S. Nagarajan et al. / Carbohydrate Research 346 (2011) 722–727
725
step in moderate to good yields and were characterized using
different spectral techniques. The existence of the b-anomeric form
in these sugar derivatives was identified from 1H NMR studies. In
compound 1e, the role of the free hydroxyl group in the formation
of inter- and intramolecular hydrogen bonding was identified from
single-crystal XRD studies, while these types of hydrogen-bonding
interactions were not present in the acetylated derivative (1d).
4.3.1. Physicochemical and spectral data for TEG-dialdehyde 2a
Compound 2a was obtained by the reaction of triethyleneglycol
ditosylate (2.291 g, 0.5 mmol) and 2-hydroxybenzaldehyde
(1.1 mL, 1 mmol) in the presence of K2CO3 as base and DMF as sol-
vent. Yield: 1.505 g (84%) as a colorless syrup; 1H NMR (CDCl3): d
10.50 (s, 2H, Ar-CHO), 7.79–7.82 (dd, J = 1.2 Hz, J = 7.5 Hz, 2H,
Ar-H), 7.49–7.54 (m, 2H, Ar-H), 6.97–7.03 (m, 4H, Ar-H), 4.24 (t,
J = 4.7 Hz, 4H, –CH2), 3.91 (t, J = 4.7 Hz, 4H, –CH2), 3.75 (s, 4H,
–CH2). 13C NMR (CDCl3): d 189.9, 161.2, 135.9, 128.2, 125.1,
121.0, 112.9, 70.9, 69.5, 68.2.
4. Experimental section
4.1. General methods
4.3.2. Physicochemical and spectral data for TEG-dialdehyde 2b
Compound 2b was obtained by the reaction of triethylene glycol
ditosylate (2.291 g, 0.5 mmol) and 2-hydroxynaphthaldehyde
(1.72 g, 1 mmol) in the presence of K2CO3 as base and DMF as sol-
vent. Yield: 1.811 g (79%) as colorless crystals; mp 122–124 °C; 1H
NMR (CDCl3): d 10.81 (s, 2H, Ar-CHO), 9.16 (d, J = 8.7 Hz, 2H, Ar-H),
7.89 (d, J = 9.0 Hz, 2H, Ar-H), 7.64 (d, J = 8.1 Hz, 2H, Ar-H), 7.47–
7.53 (m, 2H, Ar-H), 7.13–7.33 (m, 4H, Ar-H), 4.25 (t, J = 4.2 Hz,
4H, –CH2), 3.80–3.83 (m, 4H, –CH2), 3.65 (s, 4H, –CH2). 13C NMR
(CDCl3): d 190.7, 161.9, 135.9, 129.9, 128.2, 127.1, 126.7, 123.4,
123.3, 115.7, 112.5, 69.5, 68.1, 67.7. Anal. Calcd for C28H26O6: C,
73.35; H, 5.72. Found: C, 73.53; H, 5.89.
D
-Glucose,
D-xylose, 2-hydroxybenzaldehyde, 2-hydroxyna-
phthaldehyde, 4-hydroxybenzaldehyde, 2-bromo-3-pyridinecar-
boxaldehyde, 3,4,5-trimethoxybenzaldehyde, isophthalaldehyde,
thiophene-2,3-dicarboxaldehyde and benzaldehyde dimethyl ace-
tal were obtained from Sigma–Aldrich Chemicals Pvt. Ltd, USA
and were of high purity. Butyraldehyde, triethylene glycol, p-TsOH,
p-TsCl, acetylacetone and the organic catalyst (pyrrolidine) were
obtained from SRL, India. Other reagents such as hydrochloric acid,
sodium bicarbonate, NaOH, and solvents (AR Grade) were obtained
from Sd-fine, India, in high purity and were used without any fur-
ther purification. Ac2O was purchased from Fischer Chemicals Pvt.
Ltd, India. Column chromatography was performed on Silica Gel
(100–200 mesh). NMR spectra were recorded on a Bruker DRX
300 MHz instrument in either CDCl3 or DMSO-d6 (with a few drops
of CDCl3) Chemical shifts were referenced to internal TMS. Elemen-
tal analysis was performed by using a Perkin–Elmer 2400 series
CHNS/O analyser. For single-crystal XRD studies a Bruker axs
(kappa apex 2) diffractometer was used. Abbreviations such as,
‘Sac’, ‘Ar’ and ‘Alk’ correspond to ‘Saccharide’, ‘Aromatic’ and
‘Alkenic’ protons, respectively.
4.3.3. Physicochemical and spectral data for the dialdehyde 2c
Compound 2c was obtained by the reaction of triethylene glycol
ditosylate (2.291 g, 0.5 mmol) and 4-hydroxybenzaldehyde (1.22 g,
1 mmol) in the presence of K2CO3 as base and DMF as solvent.
Yield: 1.649 g (92%) as an amorphous solid; mp 79–81 °C; 1H
NMR (CDCl3): d 9.87 (s, 2H, Ar-CHO), 7.82 (d, J = 8.7 Hz, 4H, Ar-
H), 7.01 (d, J = 8.7 Hz, 4H, Ar-H), 4.21 (t, J = 4.65 Hz, 2H, –CH2),
3.90 (t, J = 4.7 Hz, 4H, –CH2), 3.77 (s, 4H, –CH2). 13C NMR (CDCl3):
d 190.8, 163.8, 131.9, 130.1, 114.9, 70.9, 69.5, 67.7. Anal. Calcd
for C20H22O6: C, 67.03; H, 6.19. Found: C, 66.81; H, 5.92.
4.2. Physicochemical and spectral data for 1-C-(4,6-O-
benzylidene-b-D-glucopyranosyl)propane-2-one (2b)
4.4. General procedure for the synthesis of ether-linked
disaccharide derivatives 3(a–d)
Compounds 1a, 1c, 1d and 1e were synthesized by adopting pro-
cedures reported in the literature,17–20,24–26 and the purity of these
samples was found to be satisfactory. The synthetic procedure for
To a solution of C-b-D-glycosylic ketone 1 (2.2 mmol) in a given
solvent were added pyrrolidine (25%) and p-TEG-dialdehyde (2c)
(1.0 mmol). After stirring at the given temperature for a period of
time, the solvent was evaporated under reduced pressure. The
crude product was slurried using silica gel and purified by column
chromatography.
1b is as follows: To a solution of 4,6-O-benzylidene-D-glucopyranose
(2.68 g, 10.0 mmol) in 1:9 H2O–THF were added NaHCO3 (3.36 g,
4 equiv) and 2,4-pentadienone (2.0 g, 2 equiv). The reaction mixture
was stirred at reflux temperature for 36 h, and then cooled to room
temperature. The resultant mixture was filtered and the residue was
washed well with CH2Cl2, whichwas then removed. The light-brown
residue thus obtained was purified by column chromatography [3:7
hexane–EtOAc] to get the expected product: Yield: 2.526 g (82%) as a
white solid; mp 142–144 °C; 1H NMR (CDCl3): d 7.46 (m, 2H, Ar-H),
7.35–7.37 (m, 3H, Ar-H), 5.47 (s, 1H, Ace-H), 4.78 (s, 1H, Sac-H),
4.22–4.27 (dd, J = 3.9 Hz, J = 10.2 Hz, 1H, Sac-H), 3.76–3.83 (ddd,
J = 3.1 Hz, J = 7.5 Hz, J = 8.9 Hz, 1H, Sac-H), 3.68 (t, J = 8.4 Hz, 1H,
Sac-H), 3.57–3.63 (m, 1H, Sac-H), 3.39–3.45 (m, 2H, Sac-H), 3.27 (t,
J = 9.2 Hz, 1H, Sac-H), 2.79–2.85 (dd, J = 3.3 Hz, J = 16.2 Hz, 1H, Sac-
H), 2.16 (s, 3H, –CH3). 13C NMR (CDCl3): d 207.1, 137.0, 129.3,
128.4, 126.4, 101.8, 81.0, 76.0, 75.1, 74.1, 70.3, 68.7, 46.0, 31.0. Anal.
Calcd for C16H20O6: C, 62.33; H, 6.54. Found: C, 61.97; H, 6.71.
4.4.1. Physicochemical and spectral data for 1,10-bis-(4-(E)-1-
(4,6-O-butylidene-b-D-glucopyranosyl)-4-(phenyl)but-3-en-2-
one)-1,4,7,10-tetraoxadecane (3a)
To a solution of 1-C-(4,6-O-butylidene-b-D-glucopyranosyl)pro-
pane-2-one (3a, 0.548 g, 2.0 mmol) in CHCl3 were added pyrroli-
dine (25 mol %) and p-TEG-dialdehyde (2b) (0.358 g, 1.0 mmol).
After stirring at room temperature for about 10 h, the solid that
formed was filtered, washed well with Et2O, and dried under vac-
uum. Yield: 806 mg (92%) as a white solid; mp 236–240 °C; 1H
NMR (CDCl3 + DMSO-d6): d 7.64 (d, J = 7.8 Hz, 4H, Ar-H), 7.53
(d, J = 15.9 Hz, 2H, Ar-H), 6.98 (d, J = 8.1 Hz, 4H, Ar-H), 6.75
(d, J = 16.5 Hz, 2H, Ar-H), 5.36 (d, J = 5.7 Hz, 2H, Sac-H), 5.24 (d,
J = 4.8 Hz, 2H, Sac-H), 4.50 (t, J = 4.7 Hz, 2H, Sac-H), 4.13 (s, 4H,
Sac-H, –CH2), 3.90–3.94 (dd, J = 3.6 Hz, J = 9.9 Hz, 2H, Sac-H), 3.75
(d, J = 3.9 Hz, 6H, Sac-H, –CH2), 3.60 (s, 8H, Sac-H), 3.30–3.50 (br,
5H, Sac-H), 2.75–3.18 (m, 7H), 1.46–1.50 (m, 4H, Sac-H), 1.22–
1.39 (m, 4H, Sac-H), 0.85 (t, J = 7.1 Hz, 6H). 13C NMR (75 MHz,
DMSO-d6): d 197.5, 160.4, 142.2, 130.3, 126.9, 124.4, 114.9,
101.2, 80.6, 76.8, 74.2, 74.0, 70.3, 69.9, 68.8, 67.5, 67.3, 42.9, 17.0,
13.8. Anal. Calcd for C46H62O16: C, 63.43; H, 7.17. Found: C,
63.11; H, 7.35.
4.3. General procedure for the synthesis of TEG-dialdehyde
derivatives 2(a–c)10
To a solution of hydroxybenzaldehyde (1 mol) in 100 mL of
DMF was added anhyd K2CO3 (19.8 g, 1.0 mol) and triethylene gly-
col ditosylate (50 mmol). After being stirred, the reaction mixture
was stirred under reflux for about 16 h, and the resulting solution
was partially concentrated in vacuum and poured into 500 mL of
water; the solid that separated was recrystallized from MeOH.

726
S. Nagarajan et al. / Carbohydrate Research 346 (2011) 722–727
4.4.2. Physicochemical and spectral data for 1,10-bis-(4-(E)-1-
(4,6-O-benzylidene-b- -glucopyranosyl)-4-(phenyl)-but-3-en-2-
one)-1,4,7,10-tetraoxadecane (3b)
To solution of 1-C-(4,6-O-benzylidene-b-D-glucopyrano-
186–188 °C; 1H NMR (CDCl3 + DMSO-d6): d 8.19 (d, J = 3.9 Hz, 1H,
Ar-H), 7.55 (d, J = 7.5 Hz, 1H, Ar-H), 7.23 (t, J = 6.0 Hz, 1H, Ar-H),
4.92 (s, 2H, Sac-H), 4.74 (s, 2H, Sac-H), 4.52 (s, 1H, Sac-H), 4.03
(d, J = 8.7 Hz, 3H, Sac-H), 3.71 (s, 1H, Sac-H), 3.55 (s, 1H, Sac-H),
3.38 (t, J = 8.0 Hz, 2H, Sac-H), 3.18–3.20 (m, 6H, Sac-H, –CH2),
2.80–2.94 (m, 6H, Sac-H, –CH2), 2.47–2.58 (m, 2H, Sac-H), 1.60–
1.62 (m, 4H, –CH2), 1.39–1.46 (m, 4H, –CH2), 0.91 (t, J = 7.2 Hz,
6H, –CH3). 13C NMR (CDCl3 + DMSO-d6): d 211.2, 210.1, 152.4,
148.8, 144.6, 141.6, 127.7, 106.9, 85.3, 81.6, 81.2, 79.5, 79.4, 75.4,
73.0, 51.7, 51.2, 50.3, 41.0, 38.9, 35.7, 22.1, 18.7. EIMS m/z: Calcd
for C32H46BrNO12, 715.2203; Found, 715.2140.
D
a
syl)propane-2-one (1b) (0.616, 2.0 mmol) in CHCl3 were added
pyrrolidine (25 mol %) and TEG-dialdehyde (2b) (0.358 g,
1.0 mmol). After stirring at room temperature for about 12 h, the
solvent was evaporated under reduced pressure. The crude product
was slurried with silica gel and purified by column chromatogra-
phy. Yield: 723 mg (77%) as a white solid; mp 230–232 °C; 1H
NMR (CDCl3 + DMSO-d6): d 8.07 (s, 6H, Ar-H), 6.78–6.73 (m, 16H,
Ar-H), 5.38–5.51 (d (br), 2H, Sac-H), 2.51–4.09 (m, 36H, Sac-H,
–CH2); 13C NMR (CDCl3 + DMSO-d6): d 197.4, 160.4, 142.3, 137.7,
130.3, 128.7, 127.9, 126.9, 126.3, 124.4, 114.9, 100.6, 81.0, 76.9,
4.6. Physicochemical and spectral data for substituted alkyl-
linked disaccharide derivatives 5b
74.2, 70.1, 68.8, 67.9, 67.3, 42.9. EIMS m/z: Calcd for C52H58O16
,
938.3725; Found, 938.3711.
To a solution of 1-C-(4,6-O-butylidene-b-D-glucopyranosyl)pro-
pane-2-one (1a, 0.548 g, 2.0 mmol) in 1:1 MeOH–CH2Cl2 were
added pyrrolidine (25 mol%) and 3,4,5-trimethoxybenzaldehyde
(4b) (0.196 g, 1.0 mmol). After stirring at 50 °C for about 36 h,
the solvent was evaporated under reduced pressure. The crude
product was slurried with silica gel and purified by column chro-
matography. Yield: 472 mg (65%) as a white solid; mp 174–
176 °C; 1H NMR (CDCl3 + DMSO-d6): d 6.34 (s, 2H, Ar-H), 4.44 (t,
J = 4.95 Hz, 2H, Sac-H), 3.98 (t, J = 10.2 Hz, 2H, Sac-H), 3.36–3.53
(m, 19H, –OMe, Sac-H, –CH2), 3.51 (t, J = 8.1 Hz, 2H, Sac-H), 3.29
(t, J = 9.6 Hz, 2H, Sac-H), 3.07–3.20 (m, 5H, Sac-H), 2.52–2.78 (m,
4H, Sac-H), 2.38–2.47 (m, 2H, Sac-H), 1.50–1.59 (m, 4H, –CH2),
1.31–1.41 (m, 4H, –CH2), 0.83 (t, J = 7.35 Hz, 6H, –CH3). 13C NMR
(CDCl3 + DMSO-d6): d 206.7, 153.0, 139.5, 104.4, 102.2, 80.4, 76.2,
76.0, 74.9, 74.6, 74.6, 70.5, 68.2, 60.6, 56.0, 49.4, 49.1, 45.7, 36.2,
35.9, 17.3, 13.8. Anal. Calcd for C36H54O15: C, 59.49; H, 7.49. Found:
C, 59.76; H, 7.27.
4.4.3. Physicochemical and spectral data for 1,10-bis-(4-(E)-1-
2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-4-(phenyl)-but-3-en-
2-one)-1,4,7,10-tetraoxadecane (3c)
To a solution of 1-C-(2,3,4,6-tetra-O-acetyl-b-
D
-glucopyrano-
syl)propane-2-one (1b, 0.776 g, 2.0 mmol) in CHCl3 were added
pyrrolidine (25 mol %) and TEG-dialdehyde (2b, 0.358 g, 1.0 mmol).
After stirring at room temperature for about 8 h, the solvent was
evaporated under reduced pressure. The crude product was slur-
ried with silica gel and purified by column chromatography. Yield:
824 mg (75%) as a colorless syrup; 1H NMR (CDCl3): 7.52 (t, 6H, Ar-
H), 6.93 (d, J = 7.8 Hz, 4H, Ar-H), 6.63 (d, J = 16.2 Hz, 2H, Ar-H), 5.23
(t, J = 9.3 Hz, 2H, Sac-H), 5.07 (t, J = 9.8 Hz, 2H, Sac-H), 4.98 (t,
J = 9.5 Hz, 2H, Sac-H), 4.23–4.29 (dd, J = 4.5 Hz, J = 12.3 Hz, 2H,
Sac-H), 3.88–4.17 (m, 16H, Sac-H, –CH2), 2.96–3.04 (dd,
J = 8.4 Hz, J = 16.2 Hz, 2H, Sac-H), 2.68 (d, J = 14.4 Hz, 2H, Sac-H),
2.00–2.04 (m, 12H, –OCOCH3); 13C NMR (CDCl3): d 196.0, 170.6,
170.2, 169.9, 169.5, 160.9, 143.5, 130.1, 126.9, 124.0, 115.0, 77.4,
75.6, 74.1, 71.6, 70.8, 69.5, 68.5, 67.5, 62.0, 42.4, 22.4, 20.6(2C),
20.5. Anal. Calcd for C54H66O24: C, 59.01; H, 6.05. Found: C,
58.61; H, 6.05.
4.7. Physicochemical and spectral data for aryl-linked
disaccharide derivative 5c
To a solution of 1-C-(4,6-O-butylidene-b-D-glucopyranosyl)pro-
pane-2-one (3a, 0.548 g, 2.0 mmol) in CHCl3 were added pyrroli-
dine (25 mol %) and isophthalaldehyde (4c) (0.134 g, 1.0 mmol).
After stirring at room temperature for about 12 h, the solvent
was evaporated under reduced pressure. The crude product was
slurried with silica gel and purified by column chromatography.
Yield: 569 mg (88%) as a white solid; mp 192–194 °C; 1H NMR
4.4.4. Physicochemical and spectral data for 1,10-bis-(4-(E)-
2,3,4-tri-O-acetyl-b-D-xylopyranosyl)-4-(phenyl)-but-3-en-2-
one)-1,4,7,10-tetraoxadecane (3d)
To a solution of 1-C-(2,3,4-tri-O-acetyl-b-D-glucopyranosyl)pro-
pane-2-one (1b, 0.632 g, 2.0 mmol) in CHCl3 were added pyrroli-
dine (25 mol %) and TEG-dialdehyde (2b, 0.358 g, 1.0 mmol).
After stirring at room temperature for about 18 h, the solvent
was evaporated under reduced pressure. The crude product was
slurried with silica gel and purified by column chromatography.
Yield: 640 mg (67%) as a colorless syrup; 1H NMR (CDCl3): d
7.40–7.73 (m, 6H, Ar-H), 6.83 (s, 4H, Ar-H), 6.55 (d, J = 15.6 Hz,
2H), 5.16 (d, J = 8.7 Hz, 2H, Sac-H), 4.87 (d, J = 9.6 Hz, 2H, Sac-H),
3.68–4.07 (m, 12H, Sac-H, –CH2), 2.43–3.35 (m, 8H, Sac-H), 1.96
(s, 9H, –COCH3). 13C NMR (CDCl3): d 195.5, 169.1, 168.9, 160.0,
131.0, 129.2, 126.0, 123.1, 114.0, 76.3, 73.8, 72.7, 70.9, 69.9, 68.6,
68.3, 66.5, 65.7, 41.40, 19.7. Anal. Calcd for C48H58O20: C, 60.37;
H, 6.12. Found: C, 60.81; H, 6.53.
(CDCl3 + DMSO-d6):
d
7.64–8.21 (m, 4H, Ar-H), 7.64 (d,
J = 16.5 Hz, 2H, Alk-H), 6.98 (d, J = 16.2 Hz, 2H, Alk-H), 5.34 (d,
J = 5.1 Hz, 2H, Sac-H), 5.23 (d, J = 4.2 Hz, 2H, Sac-H), 4.51 (s, 2H,
Sac-H), 3.94–3.97 (m, 2H, Sac-H), 3.36 (17H, Sac-H, –CH2), 3.02–
3.20 (m, 7H, Sac-H), 2.83–2.86 (m, 2H, Sac-H), 1.51–1.53 (m, 4H,
–CH2), 1.34–1.41 (m, 4H, –CH2), 0.88 (t, J = 7.1 Hz, –CH3). 13C
NMR (CDCl3 + DMSO-d6): d 197.5, 141.4, 135.1, 129.6, 127.9,
127.3, 101.3, 80.6, 76.7, 74.2, 70.1, 70.1, 67.6, 43.2, 35.9, 17.0,
13.7. Anal. Calcd for C34H46O12: C, 63.14; H, 7.17. Found: C,
63.70; H, 7.45.
4.8. Physicochemical and spectral data for aryl-linked
disaccharide derivative 5d
4.5. Physicochemical and spectral data for substituted alkyl-
linked disaccharide derivatives 5a
To a solution of 1-C-(4,6-O-butylidene-b-D-glucopyranosyl)pro-
pane-2-one (3a, 0.548 g, 2.0 mmol) in CHCl3 were added pyrroli-
dine (25 mol %) and thiophene-2,3-dicarboxaldehyde (4d, 0.140 g,
1.0 mmol). After stirring at room temperature for about 16 h, the
solvent was evaporated under reduced pressure. The crude product
was slurried with silica gel and purified by column chromatogra-
phy. Yield: 509 mg (78%) as a pale-brown solid; mp 204–206 °C;
1H NMR (CDCl3 + DMSO-d6): d 7.95 (d, J = 15.3 Hz, 1H, Alk-H),
7.78 (d, J = 15.0 Hz, 1H, Alk-H), 7.47 (s, 1H, Ar-H), 7.38 (d,
To a solution of 1-C-(4,6-O-butylidene-b-D-glucopyranosyl)pro-
pane-2-one (1a, 0.548 g, 2.0 mmol) in 1:1 MeOH–CH2Cl2 were
added pyrrolidine (25 mol %) and 2-bromo-3-pyridinecarboxalde-
hyde (4a) (0.186 g, 1.0 mmol). After stirring at 50 °C for about
48 h, the solvent was evaporated under reduced pressure. The
crude product was slurried with silica gel and purified by column
chromatography. Yield: 523 mg (73%) as
a white solid; mp

S. Nagarajan et al. / Carbohydrate Research 346 (2011) 722–727
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J = 3.9 Hz, 1H, Ar-H), 6.69 (d, J = 15.9 Hz, 1H, Alk-H), 6.61 (d,
J = 15.9 Hz, 2H, Alk-H), 5.18 (s, 2H, Sac-H), 4.95 (s, 2H, Sac-H),
4.52 (s, 2H, Sac-H), 4.04 (d, J = 7.5 Hz, 2H, Sac-H), 3.83 (s, 2H,
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Supplementary data
Crystallographic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication nos. CCDC
781163, 781164 and 702167. Copies of the data can be obtained,
free of charge, on application to CCDC, 12 Union Road, Cambridge
CB2 1EZ, UK (fax: +44 (0)1223 336033 or e-mail: deposit@ccdc.ca-
m.ac.uk). Supplementary data (ORTEP structures and associated
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