Synthesis and characterization of 3-O-esters of N-acetyl-D-glucosamine derivatives as organogelators

Article abstract of DOI:10.1039/c9nj00630c

Carbohydrate derived low molecular weight organogelators are interesting compounds with many potential applications. Selective functionalization of the different hydroxyl substituents on d-glucose and d-glucosamine resulted in small molecular gelators. Previously we have found that the C-2 acylated derivatives including esters and carbamates of 4,6-O-benzylidene protected glucose and glucosamine derivatives have shown remarkable applications as molecular gelators. In this research, in order to probe the structural influence of sugar derivatives on molecular self-assembly, we introduced acylation functional groups to the 3-hydroxyl group of 4,6-O-benzylidene acetal protected N-acetyl glucosamine derivatives. A library of fourteen ester derivatives was synthesized and characterized. The ester derivatives typically formed gels in pump oil and aqueous mixtures of dimethyl sulfoxide or ethanol. The resulting gels were characterized using optical microscopy, and rheology, etc. All alkyl ester derivatives were gelators for pump oil. A short chain ester derivative was able to form gels in a few different oils and the corresponding oil water mixtures phase selectively. The compound was also used to trap naproxen sodium and formed a stable co-gel. The controlled release of the drug from the gel to the aqueous phase was analyzed using UV-vis spectroscopy. These results show that the functionalization at the 3-OH position of the N-acetyl glucosamine derivative is a feasible strategy in designing new classes of organogelators.

Full text of DOI:10.1039/c9nj00630c

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Synthesis and Characterizations of 3-O-Esters of N-Acetyl-D-Glucosamine
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Derivatives as Organogelators
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Anji Chen, Lalith P. Samankumara, Consuelo Garcia, Kristen Bashaw, Guijun Wang,*
Department of Chemistry and Biochemistry, Old Dominion University, Norfolk, VA 23529, USA.
*Corresponding Author:
Guijun Wang, PhD
Professor of Chemistry and Biochemistry
Old Dominion University
4541 Hampton Boulevard
Norfolk, VA 23529-0126
Email: g1wang@odu.edu
Telephone: (757) 683-3781
Fax: (757) 683-4628
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Abstract:
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Carbohydrate derived low molecular weight organogelators are interesting compounds with many
potential applications. Selective functionalization of the different hydroxyl substituents on D-
glucose and D-glucosamine have resulted in small molecular gelators. Previously we have found
that the C-2 acylated derivatives including esters, carbamates of 4,6-O-benzylidene protected
glucose and glucosamine derivatives have shown remarkable applications as molecular gelators.
In this research, in order to probe the structural influence of sugar derivatives towards molecular
self-assemblies, we introduced acylation functional groups to the 3-hydroxyl group of a 4,6-O-
benzylidene acetal protected N-acetyl glucosamine derivatives. A small library of fourteen ester
derivatives were synthesized and characterized. The ester derivatives typically formed gels in
pump oil and aqueous mixtures of dimethyl sulfoxide or ethanol. The resulting gels were
characterized using optical microscopy, and rheology, etc. All alkyl ester derivatives were gelators
for pump oil. A short chain ester derivative was able to form gels in a few different oils and the
corresponding oil water mixtures phase selectively. The compound was also used to trap naproxen
sodium and formed a stable co-gel. The controlled release of the drug from gel to aqueous phase
was analyzed using UV-vis spectroscopy. These results show that the functionalization at 3-OH
position of the N-acetyl glucosamine derivative is a feasible strategy in designing new classes of
organogelators.
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Keywords: Carbohydrate derivatives, organogelators, self-assembly, phase selective gelation
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Introduction:
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Low molecular weight gelators (LMWGs) are interesting classes of compounds that have
influenced many research fields.1-3 The LMWGs form gels in organic solvents or aqueous
solutions through non-covalent intermolecular forces such as hydrogen bonding, - stacking, van
der Waals forces, etc.2, 4, 5 The resulting gels are often termed supramolecular gels and the gel to
solution transitions are reversible. There are many studies on the preparation of organogels and
hydrogels from various components including amino acids, carbohydrates. Many carbohydrate
derivatives have been found to be suitable LMWGs in different solvents; these have already been
studied for a wide variety of applications in biomedical research, environmental sciences, and other
research fields.6-14 Those organogelators that are able to form gels in various oils, have intriguing
applications for environmental sciences. These compounds have been explored for oil spill clean-
ups and the phase selective oil gelation for other applications.15-24 Several organogelators for oils
were found useful for drug delivery studies25-28 and they were also studied for food processing
since organogel matrix can help reducing oxidative damage for entrapped agents.29-31 Since
carbohydrates are readily available and biocompatible, several sugar based organogelators have
been studied for oil spill recovery.10, 32-35 In addition to environmental applications, sugar based
organogelators for oils have also found applications as optical devices and microreactors.11, 35
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We have designed and synthesized effective carbohydrate based low molecular weight
organogelators and hydrogelators using D-glucose and D-glucosamine as starting materials.36
Selectively functionalization of the hydroxyl groups and amino group at C-2 positions especially
led to several series of compounds that are effective organogelators for a wide range of solvents.37-
42
As shown in Figure 1, certain 4,6-O-benzylidene α-O-methyl-D-glucopyranoside derivatives
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with the general structures 1 and 2 are able to form gels. The dimeric esters 2 were not as effective
gelators in aqueous solutions in comparison to the C-2 monoesters 1, in which the 3-hydroxyl
group is present. The 3-hydroxyl group participates in hydrogen bonding with other sugar
derivatives and with solvents, which was important in organogelation process. However, when
longer hydrocarbon chains were used for the esters, they were able to form gels in a few organic
solvents, especially when there is an alkyne functional group present in the compounds. C-2 mono
alkyl esters with the general structure of 1 require the presence of terminal alkyne group in order
for them to form hydrogels. The glucosamine derivatives 3 are a class of effective LMWGs,
forming gels in a series of polar solvents and aqueous mixtures. The amide derivatives 3 are more
effective gelators than the corresponding esters 1; more alkyl and aryl amide derivatives were
found to be effective gelators. This was attributed to the hydrogen bonding capacity of the amido
group in 3 in comparison to ester 1.
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6
O
O
Ph
O
Ph
4
O
Ph
Ph
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O
O
O
O
R
O
O
O
2
O
O
HO
HO
1
O
O
O
R
3
O
NH
R
NH
O
OMe
OMe
OMe
OMe
O
O
R
O
O
R
1
3
2
I
R= alkyl or aromatic group
Figure 1. Structures of several classed of sugar derivatives.
Previously we have mostly focused on the synthesis and study of C-2 derivatives from 4,6-O-
benzylidene α-O-methyl-D-glucopyranoside or glucosamine derivative (1 and 3).41, 43 The crystal
structure of a C-2 ester derivative exhibited intermolecular hydrogen bonding between the 3-
hydroxyl group with ring oxygen.39 The 3-hydroxyl group in the amides 3 also participates in
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hydrogen bonding in gelation as shown in an analog through NMR analysis,44 especially in
aqueous solution. Switching the acyl functional group from the C-2 position to the C-3 positon in
amide 3 will lead to compounds I. These resulting compounds could be effective organic gelators.
The intermolecular interactions in the structures are shown in Figure 2, with the 3-hydroxy group
esterified, only the 2-NHAc can provide a hydrogen bond donor. Ester derivatives I contain
suitable functional groups that can contribute to molecular self-assemblies and gelation in organic
solvents. These compounds contain several types of intermolecular forces that may result in
supramolecular gelation. These include van der Waals interactions and hydrophobic forces from
the additional ester functions. Compound 4 was synthesized from N-acetyl glucosamine in two
steps conveniently in high yield.37, 43 It contains an acetamide functional group at the C-2 position,
which can contribute to hydrogen bonding. Using this compound as the head group, through
further functionalization at the 3-hydroxyl position, a series of compounds I can be obtained. As
shown in Figure 2, after introducing an acyl functional group, the CLogP value changed from -
0.39 for compound 4 to 2.58 for hexanoate derivative I, which indicates that the molecule will be
more soluble in organic solvents. The functionalization of the C-3 hydroxyl group of compound 4
can be done via straightforward methods in one step. In addition, the ester derivatives can he
hydrolyzed selectively over amide under alkaline conditions to afford chemical triggered gelators.
The acyl derivative can also be cleaved using certain lipases to afford enzyme-triggered gelators.
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O
Ph
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O
O
O
O
HO
O
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NH
O
OMe
NH
OMe
 interaction
O
R
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I
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hydrogen bonding
hydrophobic interaction
tPSA: 86.25
CLogP: -0.39
LogS: -1.8
R = (CH2)4CH3 tPSA: 92.32
CLogP: 2.58
LogS: -3.66
Figure 2. Rationalization of LMWGs design by esterification at 3-OH group.
Results and Discussion:
Synthesis of the 3-O-esters
In order to understand the structural influence towards gelation properties and produce sustainable
functional organogelators, we synthesized and characterized a series of compounds I. The
synthesis of these of 3-acyl derivatives is shown in Scheme 1.43 Using a combinatorial approach,
a small library of ester compounds was synthesized; these include short chain linear alkyl ester
with 4, 5, 6, 7, 11 carbons, terminal chloro or acetylene substituted alkyl derivatives, cyclohexyl
ester, and a few aromatic derivatives. The esterification using unhindered fatty acid or the
corresponding acid chloride was typically carried out at room temperature, and for certain aromatic
derivatives such as the 4-bromobenzoate the reaction requires heating and longer reaction times.
The 3-posistion of the compound 4 is sterically hindered, therefore two equivalents of acid
chlorides were necessary to obtain good yields. After these compounds were synthesized, we tested
their gelation properties in a panel of organic solvents, the results are shown in Table 1. Hexane
and water were included in the screen, and all compounds were insoluble in water and hexane at
20 mg/mL.
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O
O
RCOOH, (COCl)2
or RCOCl
O
O
O
O
O
HO
O
NH
NH
DCM, pyridine, DMAP
OMe
OMe
R
O
O
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4
I
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R:
5
, 84%
6
, 87%
8
, 80%
7
, 83%
Cl
, 84%
9
, 76%
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11
12
, 82%
, 81%
Br
OCH3
17
16
, 81%
15
, 81%
, 82%
13
14
, 85%
, 79%
O
H
O
Ph
N
O
O
O
O
O
O
O
O
O
O
Ph
O
N
18
54%
H
O
Scheme 1. Synthesis of 3-ester derivatives 5-18.
Gelation properties of the synthesized esters
As shown in Table 1, interestingly all eleven aliphatic ester derivatives prepared in this study were
able to form gels in pump oil (VWR® vacuum pump oil #19), and only one aromatic containing
derivative was effective for the oil. A majority of the alkyl esters showed gelation properties for a
mixture of water and DMSO or water and ethanol. Short chain linear aliphatic esters containing 6
to 8 carbon chains are the most versatile gelators, forming gels in at least six different solvents.
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These include compounds 6-8 with six to eight straight carbon chains, and compounds 11-12
containing 6 and 7 carbon chain with terminal acetylene. Compound 9 contains longer alkyl chain,
it formed gels in pump oil with the lowest MGC of the entire series, 4.0 mg/mL. A dimeric ester
compound 18 was also synthesized and studied, it showed effective gelation in seven of the tested
solvents, which indicates that formation of dimeric derivatives containing two sugar units is a
feasible method in achieving molecular self-assemblies. The hexanoate compound 6 was an
effective gelator for seven solvents too and at lower concentrations than compound 18. Compound
6 was selected and tested for several other oils and it formed stable gels in mineral oil (4.0 mg/mL)
and engine oil (6.7 mg/mL) too, besides pump oil. The gels were mostly opaque for aqueous
mixtures with polar solvents, and transparent for pump oil. Some photos of the gels are shown in
Figure 3.
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Table 1. Gelation properties of the synthesized compounds.
EtOH: EtOH: DMS
DMS
Pump
oil
i-
Glyc
No.
R:
Tol
S
EtOH
H2O
(1:1)
H2O O:H2O O:H2O
EG
P
PrOH
erol
(1:2)
(1:1)
(1:2)
G 6.7
c
G 6.7
G 5.0
G 5.0
5
6
S
S
S
S
S
S
o
o
o
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G
20.0
o
G 4.0
c
G 10.0 G 3.3
G 5.0
o
G 5.0 G 10.0
S
o
o
o
o
G 20.0
c
G 20.0
c
G 4.0
c
G 20.0 G 20.0 G 10.0 G 20.0 G 10.0
7
8
9
S
S
S
S
S
S
S
S
S
P
P
P
o
o
o
o
o
G 6.7
o
G 2.8
o
G 6.7
o
G 5.0
o
G 5.0 G 20.0
o
o
G 20.0
o
P
P
P
8
G 10.0
c
Cl
10
11
S
S
P
P
S
S
S
P
P
P
S
S
S
S
S
G
20.0
o
G
20.0
o
G 10.0
c
G 20.0 G 20.0 G 20.0 G 20.0
o
o
o
o
G 10.0
o
G 20.0 G 20.0 G 20.0 G 20.0
12
13
14
15
S
S
P
P
S
P
P
P
S
S
o
o
o
o
G 10.0
c
G 10.0 G 10.0
P
P
P
P
P
o
o
G 6.7
o
G 20.0
o
P
I
P
I
P
P
G
20.0
o
G 20.0
o
Br
I
P
I
P
G 20.0
o
OMe
16
17
18
S
I
S
P
P
P
S
P
I
I
I
I
P
I
P
I
P
I
P
I
G
20.0
o
G
20.0
o
G 10.0 G 20.0
G 6.7
o
G 10.0 G 10.0
P
P
5
c
c
o
o
G, gel at room temperature, the numbers are the corresponding minimum gelation concentrations
(MGCs) in mg/mL; C for clear or transparent; T, translucent; O, opaque; UG, unstable gel; I,
insoluble; P, crystallize or precipitate; S, soluble at ~20.0 mg/mL; Pump oil, VWR® vacuum pump
oil #19; Tol, toluene; EG, ethylene glycol.
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a
b
c
d
e
Figure 3. An transparent gel formed by 6 at a) 4.0 mg/mL in pump oil; b) 4.0 mg/mL in mineral
oil and c) 6.7 mg/mL in engine oil; d) an opaque gel formed by 8 in DMSO/H2O (v/v 1:1) at 5.0
mg/mL; e) an opaque gel formed by 15 in toluene at 20.0 mg/mL.
The compound 6 was then tested for phase selective gelation of oil and water mixtures. As shown
in Figure 4, the gelator was effective in selective gelation for the oil phase in presence of aqueous
phase, which contained copper sulfate to give the blue color for easy visualization of layers. The
oil gels were strong enough to hold the weight of the aqueous phases for all three samples.
a
b
c
Figure 4. The phase selective gelation by compound 6 in oil and water (CuSO4 solution) mixture:
a) Compound 6 (4.0 mg) in pump oil (1 mL) and water (1 mL). b) Compound 6 (3.0 mg) in mineral
oil (0.75 mL) and water (0.75 mL). c) Compound 6 (4.0 mg) in engine oil (0.6 mL) and water (0.6
mL).
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Gel morphology characterizations
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The optical micrographs of several representative dried gels are shown in Figure 5. The
morphology of the most versatile gelator compound 6 in different solvents are shown in Fig. 5A
and 5B. The gel in DMSO/H2O (v 1:2) formed uniform long and curved fibrous assemblies (Fig.
5A) with estimated diameter of 0.5 µm and several hundred microns in lengths, the fibers or
tubules are curved and birefringent. The gel in EtOH/H2O (v 1:1) formed long and uniform fibers
(Fig. 5B). And increasing water content to EtOH:H2O (v 1:2) the morphologies are very similar to
those of compound 6 in EtOH/H2O (v 1:1). The octanoate derivative compound 8 showed similar
gelation properties, it formed gels in six tested solvents. The morphologies of some of these dried
gels are shown in Figs 5C, D, and E. The gel of compound 8 in DMSO/H2O (v 1:2) at 5.0 mg/mL
showed similar fibrous morphologies (Fig. 5C) to compound 6 (Fig. 5A), and similar diameters.
The DMSO/H2O (v 1:1) gel however also formed uniform fibrous assemblies, but much thinner
widths in the fibers or tubules (Fig. 5D) in comparison with Fig. 5B. The EtOH/H2O (v/v 1:2) gel
also showed uniform fibrous feature with thin diameters (Fig. 5E). The gel of compound 9 in
EtOH/H2O (v/v 1:1) at 2.8 mg/mL showed uniform birefringent fibrous or tubular assemblies (Fig.
5F). One interesting observation is that if the gelators are more efficient, e.g. forming gels at lower
concentrations, the morphologies are typically long and narrow fibers. But when they are not very
efficient such as forming gels at higher MGCs such as 20 mg/mL, they usually form wider or larger
tubules and sometimes planar sheets. For example the gel formed by compound 12 in EtOH/H2O
(v/v 1:1) at 20.0 mg/mL showed planar sheets like features, these also showed liquid crystal like
optical images (Fig. 5G). The toluene gel of compound 15 formed bundles of fibers rather than
individual fibers, the morphology was not uniform as the others (Fig. 5H). And the ethanol gel of
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compound 15 exhibited more rigid rod like structures, the dried gels contain both fibers and
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crystalline planar sheets (Fig. 5I).
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48
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50
51
52
53
54
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57
58
59
60
Figure 5. Optical micrographs of the gels formed by several compounds in different solvents. A)
compound 6 in DMSO/H2O (v 1:2) at 5.0 mg/mL; B) compound 6 in EtOH/H2O (v/v 1:1) at 10.0
mg/mL; C) compound 8 in DMSO/H2O (v 1:2) at 5.0 mg/mL; D) compound 8 in DMSO/H2O (v
1:1) at 5.0 mg/mL; E) compound 8 in EtOH/H2O (v/v 1:2) at 6.7 mg/mL; F) compound 9 in
EtOH/H2O (v/v 1:1) at 2.8 mg/mL; G) compound 12 in EtOH/H2O (v/v 1:1) at 20.0 mg/mL; H)
compound 15 in toluene at 20.0 mg/mL; I) compound 15 in ethanol at 20.0 mg/mL.
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Rheological properties of the gels
5
6
7
8
The rheological properties of gels formed by compounds 6, 7 and 8 in mixed solvents of water
with DMSO or water with ethanol are shown in Figure 6a. And the rheological properties for the
oil gels are shown in Figure 6b. For all the tested gels, their storage moduli G′s are greater than
the loss moduli G″s, indicating that the gels have viscoelastic properties and are stable gels. For
the gels in aqueous mixtures, the compound 8 in DMSO/H2O (v 1:1) at 5.0 mg/mL concentration
had the highest values of G′ and G″ and it was the strongest gel among all the tested samples. And
the gel formed by compound 6 in DMSO/H2O (v 1:2) had the largest Gʹ/Gʺ values. We also carried
out the amplitude sweep experiment for these gels, and the results are shown in the SI Figures S1-
S8.
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Figure 6a. Rheological properties of the gels formed by compound 6 (EtOH/H2O, v 1:1, 10.0
mg/mL), compound 6 (EtOH/H2O, v 1:2, 3.3 mg/mL), compound 6 (DMSO/H2O, v 1:2, 5.0
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mg/mL), compound 7 (DMSO/H2O, v 1:1, 10.0 mg/mL) and compound 8 (DMSO/H2O, v 1:1, 5.0
5
6
mg/mL). Applied strain was 1% for all the samples.
7
8
9
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50
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53
54
55
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57
58
59
60
Figure 6b. Rheological properties of the gels formed by compound 6 in pump oil (4.0 mg/mL),
mineral oil (4.0 mg/mL), and engine oil (6.7 mg/mL). Applied strain was 1% for all the samples.
Thermal stability
To further test the relative thermal stability, the melting points for a few DMSO:H2O (v/v 1:1) gels
formed by compounds 5-8 with different alkyl chain length were measured. As shown in Table 2,
the melting points of gels with the same concentration range increased with an increase of the
chain length. At 10.0 mg/mL concentrations for the four gelators, compound 8 with the longest
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9
chain had the highest melting points, and compound 5 with the shortest chain had the lowest
middle-melting points among the four gelators. This trend is understandable that when increasing
the hydrophobic chain, the intermolecular interactions increases and enhance the gelation. The gels
formed by compound 7 in different concentrations were also tested, and the melting points
increased when the concentration of the gels increased. At higher concentrations the gels were
more stable, though the change in temperature is not huge, which indicates that concentration only
plays a limited role in the gel stability, however, the structures of the gelation make much bigger
differences towards stability.
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O
O
O
O
Ph
O
O
Ph
O
O
O
O
Ph
O
Ph
O
O
O
O
O
NH
O
NH
O
OCH3
NH
OCH3
O
NH
OCH3
O
O
OCH3
O
O
O
7
5
6
8
Table 2. The melting point range for some of the gels in DMSO:H2O (v/v 1:1).
Compound
G-C
(mM)
24.6
23.7
23.0
34.5
46.0
22.3
G-C (mg/mL)
T1 (°C)
T2 (°C)
T3 (°C)
number
5
6
7
7
7
8
10.0
10.0
10.0
15.0
20.0
10.0
48.7
53.6
56.2
62.4
65.7
58.7
55.4
67.2
83.5
89.0
94.3
87.6
60.7
77.6
99.4
103.4
108.4
102.3
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G-C: gelation concentration. T1: initial melting temperature when liquid was first seen. T2:
temperature when the gel is half melted. T3: the temperature of the entire gel turned into a colorless
liquid and the ball reached the bottom of the tube.
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Characterization of gelator structures using NMR spectroscopy
To elucidate the structural influences towards molecular self-assembly, we carried out the study
of 1H NMR spectroscopy at different temperatures for compounds 6 and 15. The 1H NMR spectra
of compound 15 showed shifts in some of the signals when the temperature was increased (SI
Figure S12 and S13). From 30 to 55 °C, the acetyl NH signal of compound 15 shifted from 5.84
to 5.80 ppm and the anomeric signal shifted from 4.77 to 4.78 ppm. There were also small shifts
observed in the acetal (5.57 to 5.55 ppm) and OCH3 (3.44 to 3.45 ppm) signals. These results
suggest that the NH protons participate in hydrogen bonding interactions, which contribute to the
molecular packing necessary for gelation.
1
The H NMR spectra of compound 6 are shown in Figure 7. The amide N-H signal showed the
most obvious shift among all signals, from 5.81 ppm shifted upfield to 5.77 ppm upon heating
from 30 to 55 °C, which indicates that the amide hydrogen bonding is important among the
different compounds. Other signals didn’t show significant changes, the anomeric proton and the
OCH3 both slightly shifted downfield by 0.01 ppm at higher temperature, which indicate that the
intramolecular hydrogen bonding between the NH with OCH3 slightly enhances while
intermolecular hydrogen bonding decreases. In oil and other non-polar solvents, the intermolecular
hydrogen bonding among the gelator molecules plays an important role towards the gel stability
and strength.
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5
6
 5.53 ppm
H
30 °C
7
8
9
10
11
12
13
14
15
16
6
3
O
4
5
O
O
2
 4.72
H
1
O
O
Ac
N
H
 5.32
OMe
H
 5.81
Acetal H
5.53
H-1
4.72
H-3
5.32
3.40 -OCH3
-NH-
17
18
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53
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59
60
30 °C
35 °C
H-6b
H-5
H-6a
5.81
H-2
H-4
5.53
5.53
5.53
5.53
3.40
4.72
5.31
5.31
5.31
5.31
5.80
3.41
3.41
40 °C
4.73
4.73
5.79
5.79
45 °C
50 °C
55 °C
3.41
3.41
4.73
4.73
5.78
5.77
5.53
5.31
Figure 7. The 1H NMR spectra (3.3 to 6.0 ppm) of compound 6 from 30ꢀ°C to 55ꢀ°C in CDCl3
(10.0ꢀmg/mL).
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Drug encapsulation and release
5
6
7
8
Compound 6 was also tested in a series of DMSO and water mixture by sequentially adding water
to DMSO. It formed stable gels in DMSO:H2O (v/v 1:3) at 5.0 mg/mL concentration (SI Figure
Table S6.). This compound was used for the entrapping of a model drug naproxen and the release
of naproxen from the co-gels at different time was monitored by UV-Vis spectroscopy. The UV-
vis absorbance and release% over time are shown in Figure 8. About 50% of naproxen was released
to the water phase during the first 10 h, and more slowly after that. About 75% was released to the
aqueous phase at 48 h. The naproxen co-gels was also subjected to pH=10 solution and the gel was
stable during the period of 48 hours, when naproxen release was monitored by UV-Vis
spectroscopy. This is shown in Figure S19, the naproxen release speed was almost the same as
using pH 7 water as shown in Figure 8. We tested the stability of the gel formed by compound 6
in DMSO:H2O (v/v 1:3) at 5.0 mg/mL and treated the gels with stronger base solution (pH=14),
the gel was stable for several hours but showed slow degradation over 10 hours (Figure S20). The
results indicated that the gels were stable under mild alkaline conditions and should be suitable to
use in presence of a wide pH range.
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9
naproxen
standard
1h
1
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0
2h
3h
4h
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6h
8h
10h
12h
24h
36h
48h
280
300
320
340
Wavelength (nm)
100
90
80
70
60
50
40
30
20
10
0
0
1
2
3
4
6
8
10 12 24 36 48
Time (h)
a
b
Figure 8. Release of naproxen from gel to aqueous phase. a) UV spectra of naproxen timed release,
the gel was formed by 7.5 mg of compound 6 in 1.5 mL DMSO:H2O (v/v 1:3) with 0.3 mg of
naproxen, then 1.5 mL of water (pH 7) was added to the top of the gel; naproxen control was
prepared by dissolving 0.3 mg of naproxen in 3 mL of water (pH 7). b) The % release at different
times based on the UV absorbance at 331 nm.
Conclusions
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In summary, a series of fourteen 3-O-ester derivatives of 2-acetamido-2-deoxy-4,6-O-benzylidene
methyl-α-D-glucopyranoside were synthesized and characterized. All the ten synthesized alkyl
ester derivatives were effective gelators for pump oil and many of them were found to be effective
gelators for aqueous mixtures of ethanol and DMSO. In contrast, the aromatic ester derivatives did
not perform well, only the benzoate derivative formed gels in oil and the p-bromobenzoate formed
two organogels. The dimeric ester derivative 18 can be considered as covalently linking two
monomer (compound 5), the dimerization resulted in more gelation tendency in organic solvents.
Optical microscopy studies showed that the gelators formed typically uniform fibrous network and
some derivatives formed crystalline sheets. The rheological studies showed that the storage moduli
G′s for the gels were higher than the loss moduli G″s indicating the viscoelastic properties of the
gels. The hexanote derivative 6 was able to encapsulate naproxen and form a co-gel, and the gelator
showed sustained release of the trapped naproxen from gel to aqueous phase. In addition, the
hexanoate compound 6 was also effective in phase selective gelation for several different oils in
presence of aqueous phase. The 1H NMR spectra of compound 6 at different temperature showed
that the amide function played an important role in the intermolecular hydrogen bonding during
molecular assembling. Since this new class of carbohydrate derived esters can be synthesized via
straightforward methods from readily available starting materials, they could have many practical
applications including oil spill cleanup. The systematic derivatization at the C-3 position of N-
acetyl glucosamine derivatives led to a new class of low molecular weight organo and
hydrogelators. The general structural features obtained from this series of compounds can be
applied to other sugar derivatives and afford functional and versatile organogelators.
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Experimental Section
5
6
General method and materials
7
8
9
Reagents and solvents were used as they were received from the suppliers. All purification was
conducted by flash chromatography using 230-400 mesh silica gel with a gradient of solvent
systems. 1H NMR and proton-decoupled 13C NMR spectra were obtained with Bruker 400 MHz
spectrometers in CDCl3. The chemical shifts were reported using CDCl3/d6-DMSO calibrated at
7.26/2.50 ppm and 77.00/39.50 ppm respectively. Melting point measurements were carried out
using a Fisher Jones melting point apparatus. Rheology experiment was done using a HR-2
Discovery Hybrid Rheometer from TA instrument and a 25 mm Peltier Plate. FTIR experiments
were conducted using liquid or solid samples directly. The molecular mass was measured using
LCMS on an Agilent 6120B Single Quad Mass Spectrometer coupled with LC1260 system and
Shimazu LC 2030C system with LCMS 2030 Mass Spectrometer.
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Optical microscopy
A small amount of the gels was placed on a clean glass slide and this was observed under an
Olympus BX60M optical microscope and the Olympus DP73-1-51 high performance 17MP digital
camera with pixel shifting and Peltier cooled. The imaging software for image capturing was
CellSens 1.11. For aqueous DMSO mixtures, the gel was left air dried for a day or so, for other
solvents the slides were observed directly.
Gelation test
About 2 mg of dried compound was placed in a 1 dram glass vial and the corresponding solvent
was added to obtain a concentration of 20 mg/mL. The mixture was then heated until the solid was
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fully dissolved, sometimes sonication was needed to dissolve the sample, and then the solution
was allowed to cool to room temperature and left standing for 30 minutes. If a stable gel formed
(observed by inverting the vial), it was then serially diluted till the minimum gelation concentration
(MGC), which is the concentration prior to unstable gelation, was obtained.
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Phase selective gelation test for oil and water mixture: The test results of compound 6 in several
oil and water mixtures are shown in Figure 5. General method: compound 6 (4.0 mg) was added
to the mixture of 1 mL pump oil and 1 mL of copper sulfate solution. Then the sample vial was
heated till all dissolve then was left cooling to rt, 10 minutes later, the pump oil gel was formed
and strong enough to hold the aqueous phase. The other oils were tested similarly, so only the
quantities of samples are given here: 3 mg of compound 6, 0.75 mL of mineral oil and 0.75 mL of
copper sulfate solution. For engine oil the time waiting for gelation was 1 hour, the gel was
prepared using 4 mg of compound 6, 0.6 mL of engine oil and 0.6 mL of copper sulfate solution.
Rheological analyses
The rheological behavior of the gel was investigated with an HR-2 Discovery hybrid rheometer
from TA Instruments with TRIOS software. A sample (approximately 1mL of the gel) was placed
on the steel plate of the rheometer. The cone geometry is a 25 mm Peltier plate with a gap of 100
μm. The experimental temperature was 25 °C, and the sample was subjected to amplitude sweep
for oscillation strain from 0.125 to 100 %. A frequency sweep was then performed for the sample
in the range of 0.1 to 100 rad/s for the angular frequency. The results were expressed as the storage
modulus (G′) and loss modulus (G″) as a function of angular frequency.
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Measurement of melting point ranges of gels
5
6
7
8
The gelator was dissolved in a small vial at the certain gelation concentration and heated to form
the solution. The hot solution was transferred to an NMR tube or a narrow glass tube, where it was
allowed to cool down to form the gel. A metal ball was placed on top of the gel. The NMR tube
was immersed in an oil bath which was heated gradually. T1 is the temperature of the initial melting
at which liquid was first seen. T2 is the temperature at which the gel is estimated to be half melted.
And T3 is the temperature at which the entire gel turned into a colorless liquid when the ball fell
towards the bottom of the tube.
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Naproxen release study
The gels were formed by adding 7.5 mg compound 6, followed by 1.5 mL of DMSO:H2O (v/v
1:3) containing 0.3 mg Naproxen. The mixture was heated and cooled to form a stable gel in a vial.
Water (1.5 mL, pH = 7 or 10) was pipetted on top of the gel carefully. The aqueous phased was
periodically transferred to a quartz cuvette and the UV-Vis spectrum was measured. The naproxen
standard was prepared by dissolving 0.3 mg naproxen sodium in 3 mL of water (pH = 7). All
measurements were carried out using Thermo Scientific™ Evolution™ 201 UV-Visible
spectrophotometer.
Liquid chromatography-mass spectrometer (LC-MS) conditions
The molecular mass acquisition was performed using an Agilent 1260 Infinity LC system coupled
to a G6120B single quadrupole mass spectrometer with an atmospheric pressure ionization
electrospray (API-ES). The analytical column was an Agilent poroshell 120 EC-C18 4.6 mm × 50
mm column with 2.7 μm particle size. The mobile phase was 0.1% formic acid in acetonitrile/water
(70/30, v/v) with ejection volume 5 µL and 8 minutes of total run time typically. The flow rate was
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0.40 mL/min and the column temperature set at 25 °C. The diode-array detector (DAD) was 254
nm. Agilent OpenLAB CDS ChemStation (Version C.01.05) was used for data processing. The
ESI spray voltage was set at 4000 V, the source temperature was 350 °C and the nebulizer gas
setting was 35 psi.
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General procedure for the synthesis of compounds 5-18
To a suspension of 4 (100 mg, 0.313 mmol, 1 equiv) in CH2Cl2 (4 mL, anhydrous) at 0 °C was
added pyridine and DMAP (6 mg, 0.047 mmol, 0.15 equiv) under nitrogen atmosphere and
protected from moisture using a drying tube. The resulting mixture was stirred at 0 °C for about
30 minutes. Two equivalents of acyl chloride (commercially available or prepared in situ by
treating the corresponding acid with oxalyl chloride) was then added drop-wise to the reaction
mixture followed by stirring at room temperature for 6 hours unless otherwise stated. TLC (5%
1
MeOH/CH2Cl2) and H NMR spectrum of the reaction mixture indicated the complete
consumption of the starting material to the desired product. The reaction was then quenched with
satd. NaHCO3 (aq. 5 mL) and the phases were then separated and the aqueous phases was further
extracted with CH2Cl2 (15 mL x 2). The combined organic phases were dried with anhydrous
Na2SO4, filtered and concentrated to afford the crude product, which was purified by column
chromatography to obtain the desired product. The detailed synthesis for compound 5 and di-ester
compound 18 are included only; and for all other compounds the amount of the reagents, yield, Rf
value and characterization data of the products are listed respectively.
Synthesis of 3-O-pentanoyl 2-acetamido-2-deoxy-4,6-O-benzylidene methyl-α-D-
glucopyranoside 5. Pyridine (0.12 mL, 1.55 mmol, 5 equiv) was added followed by DMAP (6.0
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mg, 0.047 mmol, 0.15 equiv) to a mixture of compound 4 (100 mg, 0.313 mmol, 1 equiv) in CH2Cl2
and the resulting mixture was stirred at 0 °C for about 30 minutes. Pentanoyl chloride (0.626 mmol,
2 equiv) in 1 mL of CH2Cl2 was then added drop wise and the reaction mixture was stirred for
about 6 hours at room temperature. The product was obtained as a white solid (107 mg, 84%). Rf
= 0.45 in 60% EtOAc/hexanes, m.p. 133.0-135.0 °C, 1H NMR (CDCl3, 400 MHz)  7.48-7.45 (m,
2H), 7.38-7.36 (m, 3H), 5.83 (d, J = 9.5 Hz, 1H), 5.55 (s, 1H), 5.34 (t, J = 10.0 Hz, 1H), 4.75 (d,
J = 3.6 Hz, 1H), 4.38-4.30 (m, 2H), 3.93-3.87 (m, 1H), 3.81 (t, J = 10.1 Hz, 1H), 3.74 (t, J = 9.5
Hz, 1H), 3.43 (s, 3H), 2.34 (dt, J = 7.4, 2.9 Hz, 2H), 1.97 (s, 3H), 1.61-1.55 (m, 2H), 1.35-1.28
(m, 2H), 0.87 (t, J = 7.3 Hz, 3H); 13C NMR (CDCl3, 100 MHz)  174.3, 169.9, 137.0, 129.0, 128.2,
126.1, 101.5, 99.1, 79.1, 69.9, 68.9, 62.8, 55.3, 52.6, 34.0, 27.1, 23.2, 22.1, 13.6. LC-MS (ESI+)
cald C21H30NO7 [M + H]+ 408.2 found 408.2.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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28
29
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31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis
of
3-O-hexanoyl
2-acetamido-2-deoxy-4,6-O-benzylidene
methyl-α-D-
glucopyranoside 6. Pyridine (0.12 mL, 1.55 mmol), DMAP (6.0 mg, 0.047 mmol), compound 4
(100 mg, 0.313 mmol, 1 equiv) and hexanoyl chloride (0.086 mL, 0.618 mmol, 2 equiv) were
added similarly as above. The product was obtained as a white solid (114 mg, 87%). Rf = 0.55 in
60% EtOAc/hexanes, m.p. 142.0-144.0 °C,1H NMR (CDCl3, 400 MHz) δ 7.38-7.36 (m, 2H), 7.29-
7.26 (m, 3H), 5.73 (d, J = 9.4 Hz, 1H), 5.46 (s, 1H), 5.24 (t, J = 10.0 Hz, 1H), 4.65 (d, J = 3.6 Hz,
1H), 4.29-4.21 (m, 2H), 3.83-3.77 (m, 1H), 3.71 (t, J = 10.1 Hz, 1H), 3.64 (t, J = 9.4 Hz, 1H), 3.33
(s, 3H), 2.30-2.17 (m, 2H), 1.88 (s, 3H), 1.55-1.47 (m, 2H), 1.21-1.16 (m, 4H), 0.76 (t, J = 6.9 Hz,
3H); 13C NMR (CDCl3, 100 MHz) δ 174.3, 169.9, 137.1, 129.0, 128.2, 126.1, 101.5, 99.1, 79.1,
68.9, 62.8, 55.3, 52.6, 34.3, 31.1, 24.7, 23.2, 22.2, 13.8. LC-MS (ESI+) cald C22H32NO7 [M + H]+
422 found 422.
25

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4
5
6
Synthesis
of
3-O-hepanoyl
2-acetamido-2-deoxy-4,6-O-benzylidene
methyl-α-D-
7
8
9
glucopyranoside 7. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and Heptanoyl chloride (0.096 mL, 0.618
mmol, 2 equiv) were added were added similarly as above. The product was obtained as a white
solid (112 mg, 83%). Rf = 0.6 in 60% EtOAc/hexanes, m.p. 137.0-139.0 °C, 1H NMR (CDCl3, 400
MHz) δ 7.47-7.41 (m, 2H), 7.37-7.32 (m, 3H), 5.82 (d, J = 9.4 Hz, 1H), 5.52 (s, 1H), 5.30 (t, J =
10.1 Hz, 1H), 4.72 (d, J = 3.6 Hz, 1H), 4.36-4.27 (m, 2H), 3.91-3.82 (m, 1H), 3.78 (t, J = 10.1 Hz,
1H), 3.71 (t, J = 9.5 Hz, 1H), 3.40 (s, 3H), 2.30 (dt, J = 7.4, 3.6 Hz, 2H), 1.95 (s, 3H), 1.58-1.53
(m, 2H), 1.31-1.18 (m, 6H), 0.84 (t, J = 6.7 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 174.3, 169.9,
137.0, 129.0, 128.2, 126.1, 101.5, 99.1, 79.1, 69.9, 68.9, 62.8, 55.3, 52.6, 34.3, 31.4, 28.6, 25.0,
23.2, 22.4, 14.0. LC-MS (ESI+) cald C23H34NO7 [M + H]+ 436 found 436.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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29
30
31
32
33
34
35
36
37
38
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis
of
3-O-octanoyl
2-acetamido-2-deoxy-4,6-O-benzylidene
methyl-α-D-
glucopyranoside 8. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and Octanoyl chloride (0.11 mL, 0.618 mmol,
2 equiv) were added similarly as above. The product was obtained as a white solid (111 mg, 80%).
Rf = 0.6 in 60% EtOAc/hexanes, m.p. 128.0-130.0 °C, 1H NMR (CDCl3, 400 MHz) δ 7.48-7.45
(m, 2H), 7.38-7.35 (m, 3H), 5.82 (d, J = 9.6 Hz, 1H), 5.55 (s, 1H), 5.34 (t, J = 10.1 Hz, 1H), 4.75
(d, J = 3.6 Hz, 1H), 4.38-4.30 (m, 2H), 3.93-3.87 (m, 1H), 3.81 (t, J = 10.2 Hz, 1H), 3.74 (t, J =
9.4 Hz, 1H), 3.43 (s, 3H), 2.39-2.27 (m, 2H), 1.98 (s, 3H), 1.63-1.56 (m, 2H), 1.29-1.23 (m, 8H),
0.87 (t, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 174.3, 169.9, 137.1, 129.0, 128.2, 126.1,
101.5, 99.1, 79.1, 69.9, 68.9, 62.8, 55.3, 52.6, 34.3, 31.6, 28.93, 28.87, 25.0, 23.2, 22.6, 14.0. LC-
26

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4
MS
(ESI+)
cald
C24H36NO7
[M
+
H]+
450
found
450.
5
6
7
8
9
Synthesis of 3-O-dodecanoyl 2-acetamido-2-deoxy-4,6-O-benzylidene methyl-α-D-
glucopyranoside 9. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and Lauroyl chloride (0.626 mmol, 2 equiv)
were added similarly as above. The product was obtained as a white solid (120 mg, 76%). Rf = 0.6
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
1
in 60% EtOAc/hexanes, m.p. 96.0-98.0 °C, H NMR (CDCl3, 400 MHz) δ 7.47-7.40 (m, 2H),
7.37-7.30 (m, 3H), 5.81 (d, J = 9.5 Hz, 1H), 5.53 (s, 1H), 5.31 (t, J = 10.0 Hz, 1H), 4.72 (d, J =
3.7 Hz, 1H), 4.37-4.27 (m, 2H), 3.91-3.83 (m, 1H), 3.80 (t, J = 10.1 Hz, 1H), 3.71 (t, J = 9.4 Hz,
1H), 3.40 (s, 3H), 2.34-2.25 (m, 2H), 1.95 (s, 3H), 1.61-1.52 (m, 2H), 1.34-1.14 (m, 16H), 0.88 (t,
J = 6.9 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 174.3, 169.9, 137.1, 129.0, 128.2, 126.1, 101.5,
99.1, 79.1, 69.9, 68.9, 62.8, 55.3, 52.6, 34.3, 31.9, 29.59, 29.57, 29.4, 29.3, 29.2, 29.0, 25.0, 23.2,
22.7, 14.1. LC-MS (ESI+) cald C28H44NO7 [M + H]+ 506 found 506.
Synthesis of 3-O-4’-chlorobutanoyl 2-acetamido-2-deoxy-4,6-O-benzylidene methyl-α-D-
glucopyranoside 10. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and 4-Chlorobutyryl chloride (0.07 mL, 0.626
mmol, 2 equiv) were added similarly as above. The product was obtained as an off-white solid
1
(111 mg, 84%). Rf = 0.5 in 60% EtOAc/hexanes, m.p. 129.0-131.0 °C, H NMR (CDCl3, 400
MHz) δ 7.47-7.41 (m, 2H), 7.38-7.32 (m, 3H), 5.79 (d, J = 9.6 Hz, 1H), 5.53 (s, 1H), 5.31 (t, J =
10.0 Hz, 1H), 4.71 (d, J = 3.7 Hz, 1H), 4.39-4.28 (m, 2H), 3.91-3.84 (m, 1H), 3.79 (t, J = 10.1 Hz,
1H), 3.72 (t, J = 9.5 Hz, 1H), 3.52 (t, J = 6.2 Hz, 2H), 3.41 (s, 3H), 2.54-2.47 (m, 2H), 2.08-2.00
13
(m, 2H), 1.96 (s, 3H); C NMR (CDCl3, 100 MHz) δ 173.0, 170.0, 136.9, 129.1, 128.2, 126.1,
27

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5
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101.6, 99.0, 79.0, 70.5, 68.9, 62.8, 55.3, 52.4, 43.7, 31.3, 27.7, 23.2. LC-MS (ESI+) cald
C20H27ClNO7 [M + H]+ 428 found 428.
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
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33
34
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38
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41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
Synthesis of 3-O-5’-hexynoyl 2-acetamido-2-deoxy-4,6-O-benzylidene methyl-α-D-
glucopyranoside 11. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and 5-hexynoyl chloride (0.626 mmol, 2
equiv) were added similarly as above. The product was obtained as a white solid (105 mg, 81%).
Rf = 0.3 in 60% EtOAc/hexanes, m.p. 162.0-164.0 °C, 1H NMR (d6-DMSO, 400 MHz) δ 7.95 (d,
J = 9.4 Hz, 1H), 7.41-7.32 (m, 5H), 5.65 (s, 1H), 5.18 (t, J = 10.2 Hz, 1H), 4.67 (d, J = 3.5 Hz,
1H), 4.27-4.16 (m, 2H), 3.85-3.76 (m, 2H), 3.75-3.67 (m, 1H), 3.36 (s, 3H), 2.76 (t, J = 2.6 Hz,
1H), 2.40-2.27 (m, 2H), 2.14 (dt, J = 7.1, 2.6 Hz, 2H), 1.82 (s, 3H), 1.71-1.58 (m, 2H); 13C NMR
(d6-DMSO, 100 MHz) δ 171.7, 169.6, 137.3, 128.8, 128.0, 126.0, 100.3, 98.8, 83.5, 78.8, 71.6,
69.4, 67.8, 62.6, 54.9, 51.2, 32.3, 23.7, 22.2, 16.8. LC-MS (ESI+) cald C22H28NO7 [M + H]+ 418,
found 418.
Synthesis of 3-O-6’-heptynoyl 2-acetamido-2-deoxy-4,6-O-benzylidene methyl-α-D-
glucopyranoside 12. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and 6-heptynoyl chloride (0.626 mmol, 2
equiv) were added similarly as above. The product was obtained as a white solid (111 mg, 82%).
Rf = 0.45 in 60% EtOAc/hexanes, m.p. 159.0-161.0 °C, 1H NMR (d6-DMSO, 400 MHz) δ 7.94 (d,
J = 9.4 Hz, 1H), 7.39-7.34 (m, 5H), 5.64 (s, 1H), 5.17 (t, J = 9.6 Hz, 1H), 4.67 (d, J = 3.5 Hz, 1H),
4.27-4.16 (m, 2H), 3.84-3.76 (m, 2H), 3.75-3.67 (m, 1H), 3.36 (s, 3H), 2.72 (t, J = 2.6 Hz, 1H),
2.34-2.18 (m, 2H), 2.08 (dt, J = 7.0, 2.6 Hz, 2H), 1.82 (s, 3H), 1.60-1.50 (m, 2H), 1.44-1.34 (m,
28

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2
3
4
5
6
7
8
9
2H); 13C NMR (d6-DMSO, 100 MHz) δ 172.0, 169.6, 137.3, 128.8, 128.0, 126.0, 100.3, 98.9, 84.0,
78.8, 71.2, 69.3, 67.8, 62.6, 54.9, 51.2, 33.0, 27.0, 23.7, 22.3, 17.3. LC-MS (ESI+) cald C23H30NO7
[M + H]+ 432.2 found 432.2.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
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59
60
Synthesis of 3-O-cyclohexanoyl 2-acetamido-2-deoxy-4,6-O-benzylidene methyl-α-D-
glucopyranoside 13. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), compound 4 (100 mg, 0.313 mmol,
1 equiv) and Cyclohexanecarbonyl chloride (0.2 mL, 1.24 mmol, 4 equiv) were added similarly as
above. Then the reaction mixture was stirred for about 90 minutes at 0 °C. The product was
obtained as a white solid (106 mg, 79%). Rf = 0.22 in 50% EtOAc/hexanes. m.p. 175.0-177.0 C,
1H NMR (CDCl3, 400 MHz) δ 7.47 (m, 2H), 7.39-7.35 (m, 3H), 5.80 (d, J = 9.6 Hz, 1H), 5.55 (s,
1H), 5.34 (t, J = 10.0 Hz, 1H), 4.74 (d, J = 3.6 Hz, 1H), 4.40-4.31 (m, 2H), 3.92-3.86 (m, 1H),
3.81 (t, J = 10.1 Hz, 1H), 3.74 (t, J = 9.6 Hz, 1H), 3.43 (s, 3H), 2.35 (tt, J = 11.1, 3.6 Hz, 1H), 1.97
(s, 3H), 1.86 (m, 2H), 1.76-1.72 (m, 2H), 1.65-1.61 (m, 1H), 1.50-1.37 (m, 2H), 1.33-1.20 (m, 3H);
13C NMR (CDCl3, 100 MHz) δ 176.5, 169.9, 137.1, 129.0, 128.2, 126.1, 101.4, 99.1, 79.2, 69.6,
68.9, 62.9, 55.3, 52.6, 43.1, 28.93, 28.87, 25.7, 25.3, 25.2, 23.2. LC-MS (ESI+) cald C23H32NO7
[M + H]+ 434.2 found 434.2.
Synthesis
of
3-O-benzoyl
2-acetamido-2-deoxy-4,6-O-benzylidene
methyl-α-D-
glucopyranoside 14. Pyridine (0.12 mL, 1.55 mmol, 5 equiv), DMAP (6.0 mg, 0.047 mmol, 0.15
equiv), compound 4 (100 mg, 0.313 mmol, 1 equiv) and Benzoyl chloride (0.070 mL, 0.618 mmol,
2 equiv) were added similarly as above. The product was obtained as a white solid (112 mg, 85%).
Rf = 0.45 in 60% EtOAc/hexanes, m.p. 194.0-196.0 C, 1H NMR (CDCl3, 400 MHz) δ 8.05-8.03
(m, 2H), 7.59-7.54 (m, 1H), 7.47-7.42 (m, 4H), 7.34-7.31 (m, 3H), 5.89 (d, J = 9.6 Hz, 1H), 5.64-
29