Synthesis and characterization of monosaccharide lipids as novel hydrogelators

Article abstract of DOI:10.1016/j.carres.2006.01.023

Self-assembly of small molecules is a useful strategy for forming functional supramolecular structures. Three new series of methyl α-d-glucopyranoside derivatives, including esters and carbamates, have been synthesized and characterized. Several of these

Full text of DOI:10.1016/j.carres.2006.01.023

Carbohydrate Research 341 (2006) 705–716
Synthesis and characterization of monosaccharide lipids as novel
hydrogelators
Guijun Wang,* Sherwin Cheuk, Kristopher Williams, Vibha Sharma,
Lousi Dakessian and Zeus Thorton
Department of Chemistry, University of New Orleans, New Orleans, LA 70148, USA
Received 20 September 2005; received in revised form 18 December 2005; accepted 10 January 2006
Available online 17 February 2006
Abstract—Self-assembly of small molecules is a useful strategy for forming functional supramolecular structures. Three new series of
methyl a-D-glucopyranoside derivatives, including esters and carbamates, have been synthesized and characterized. Several of these
compounds are excellent hydrogelators and formed interesting self-assembled network structures, including birefringent fibers and
tubules. The gelation properties depend on the acyl chain length and the headgroup structures. Small molecule sugar-based hydro-
gelators have potential applications in drug delivery and enzyme immobilization.
ꢀ 2006 Elsevier Ltd. All rights reserved.
Keywords: Monosaccharides; Lipids; Self-assembly; Hydrogelators; Organogelators
1. Introduction
processes are typically reversible because of the non-
covalent interactions between the molecules. These
molecules have potential applications in forming liquid
crystalline materials, as templates for synthesizing other
novel materials, and as matrices for separating peptides
and amino acids.4,5 Polymer hydrogels are useful for
drug delivery, tissue engineering, enzyme immobiliza-
tion, and controlled release of other biological
agents.6a,b,7a,b Polysaccharide gels have been widely
utilized for DNA and protein purification and enzyme
immobilization. Supramolecular hydrogels are formed
by LMWOs in water through non-covalent forces. They
are a interesting new class of soft materials that also
have important applications in biomaterials and phar-
maceutical research.8–10 These self-assembled supramo-
lecular gels have the advantage that the monomers are
easy to prepare and the resulting materials can have tun-
able physical properties. Small molecules can be synthe-
sized and purified to give materials with a single
molecular weight, as compared to polymers, which have
a distribution of molecular weights. Their structure can
also be readily modified to introduce functional groups
that can give rise to desired physical properties. Revers-
ible physical gelation may also have the advantage of
Carbohydrates are abundant natural products and read-
ily available chiral compounds. They contain all of the
important elements necessary to prepare highly func-
tional and synthetically flexible units, but they are the
most complex and structurally dense of all naturally
occurring materials. Attempts to overcome this com-
plexity and integrate the rich functionality and the chi-
rality of carbohydrates into structural units that self-
assemble into grand architectures are very important
to advance carbohydrate chemistry. Soft materials
formed by carbohydrates and lipids are biocompatible
and have potential uses in many biomedical areas and
as biodegradable materials.
Small molecule self-assembly through non-covalent
forces can afford interesting soft materials, such as
hydrogels or organogels. Low molecular weight organo-
gelators (LMWOs) are small molecules that can form
gels in organic solvents or water.1–3 The gelation
*
Corresponding author. Tel.: +1 504 280 1258; fax: +1 504 280
6860; e-mail: gwang2@uno.edu
0008-6215/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2006.01.023

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G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
entrapping biomolecules in the matrix, without affecting
the properties of the entrapped agents. The non-
covalent interactions between the molecules make the
gels easier to dissolve or break down than polymer gels,
thus allowing the entrapped substances to be separated
readily.
ral chiral compounds with multiple sites available for
functionalization. The creation of novel functional bio-
compatible materials from carbohydrates is important
for the advancement of carbohydrate chemistry and
biomaterials research. Chirality in supramolecular
structures may be useful in molecular recognition with
other chiral compounds. These functional materials
have potential applications in drug delivery, tissue engi-
neering, and as biocompatible materials. As part of our
efforts to discover novel functional biocompatible mate-
rials, we designed and synthesized a series of D-glucose-
based lipids and found that they are excellent gelators in
water and other solvents.
Many glycolipids and other small sugar derivatives
can form gels in organic solvents, but less frequently
in water. Compound 4 is a simple and commercially
available glucose derivative, which can form gels in
organic solvents but not in water.9 Modifying its struc-
ture by introducing short alkyl chains could potentially
lead to good gelators in water or organic solvents. The
structures of three molecular classes, (A, B, and C,
Fig. 2) depending on the positions of functionalization,
are shown in Figure 2. Inspired by the structures of
hydrogelators 1–3, we envisioned the incorporation of
short chain fatty acyl unit to the 2 or 3-hydroxyl groups
via ester or carbamate linkages (B and C) could poten-
tially lead to small molecule hydrogelators and the
diester or dicarbamate A could be potential organogela-
tors. The hydroxyl groups and amide groups can pro-
vide hydrogen-bonding interactions. The incorporation
of terminal acetylene groups may reduce the acyl chain
packing order and therefore increase solubility to some
extent. It can also be used as a group that allows further
structural modification.
Low molecular weight hydrogelators have a variety of
structures, including, but not limited to, ureas,11,12 sac-
charides,13a,b,14–16 amino acids,17,18,19a–d,20–22 nucleo-
tides,23 nucleosides,24 and other structural classes.25–29
Many of them were discovered by serendipity, while
some were discovered by rational design or combinato-
rial chemistry.8,16 Several examples of existing hydro-
gelators (1–3) are shown in Figure 1. Mono-urea serine
derivative 1 can form gels in pure water at a concentra-
tion of 0.8–1 wt %.12 The hydrogen bonds between the
urea moiety allow the molecules to self-assemble into a
one-dimensional array and the short alkyl group pro-
vides flexibility. The short chain glucose and galactose
amino acid lipids 2 and 3 were discovered by combinato-
rial chemistry and shown to be effective hydrogela-
tors.8,16 They can be used to immobilize enzymes and
form protein microarrays. From an examination of the
structures of small molecule hydrogelators, the common
features of good hydrogelators that are apparent is a
rigid region that can form hydrogen-bonding interac-
tions, and a flexible short alkyl chain that will allow
the molecules to interact with each other through hydro-
phobic forces.
Because of the great potential of hydrogelators, we are
interested in discovering new biocompatible hydrogela-
tors with straightforward structures, which will render
large-scale synthesis more feasible. Carbohydrates are
ideal starting materials because they are abundant natu-
O
H
O
O
O
H
N
N
OH
O
O
O
N
H
OH
H
N
H
N
O
O
N
H
OH
O
O
O
O
O
O
OEt
HO
HO
OH
NHAc
O
HO
OH
O
O
1
3
2
Figure 1. Structures of some hydrogelators (1–3).
O
O
O
O
X
O
O
Ph
Ph
O
Ph
O
O
O
O
O
Ph
O
X
HO
O
O
O
OCH3
OCH3
OH
O
OCH3
O
O
O
HO
OH
X
X
OCH3
4
n
Y
Y
Y
Y
A
C
B
X = NH, CH2, Y = CH3, or
C
CH
n = 0-5
Figure 2. Structures of the designed hydrogelators.

G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
707
2. Results and discussion
to the diol, mainly the 2-O-monoester (compound B)
was obtained, together with small amount of A and C
as well. It is known that esterification generally favors
the introduction of the acyl group at the 2-position of
a glucose derivative. If the acyl group is not bulky, then
esterification at 3-O is also observed. The 2-O-mono-
ester is probably the kinetic product and is formed first,
the 3-O-monoester is also formed in a small amount,
and either product can react further to give the diester.
Because we use less acylating agent comparing to the
diol in the headgroup, this reduces the amount of
diester. Therefore, we can obtain all three products in
one-pot. These esters can be separated by flash chroma-
tography on silica gel using a gradient of solvent systems
(hexane/ethyl acetate from 95:5 to 75:25). We synthe-
sized a series of these glucose derivatives and tested their
gelation properties in several solvents. These include
some acetylene containing lipids with the general struc-
tures of 5A–10A, 5B–10B, and 5C–9C.
To synthesize the designed compounds efficiently, reac-
tions were carried out in one-pot to produce the three
products A, B, and C, which were then isolated by chro-
matography. This way, a small library of compounds
was synthesized rapidly. The screening of these com-
pounds will quickly give us information about structural
influences on gelation properties. The structure–gelation
properties obtained here can be used to design other
effective gelators.
Compound 4 was synthesized readily by treating
methyl a-D-glucopyranoside with dimethoxylbenzyled-
ene acetal and a catalytic amount of p-toluenesulfonic
acid (PTSA) in dimethyl formamide (DMF). Com-
pounds A, B, and C were synthesized by esterification
of the hydroxyl groups on the monosaccharide deriva-
tive 4 by the corresponding acid chlorides (Scheme 1).
By controlling the ratio of the acid and the diol, three
products were obtained in this reaction. We found that
when using about 2 equiv of acid, typically two products
were obtained: the diester A and the 2-O-monoester B
although in theory only the diester A should be
obtained. When the acid was used in 1–1.3 equiv relative
For structural comparison purposes, we also synthe-
sized the short-chain carbamate analogs 11A–12C
(Fig. 3). They were synthesized via similar methods as
mentioned above using the corresponding isocyanates
and isolated by flash chromatography. The carbamates
HO
(COCl)2
n
Cl
4
n
O
O
O
O
O
O
O
O
Ph
+
O
Ph
O
Ph
O
O
O
HO
O
O
OCH3
OH
OCH3
OCH3
O
+
O
O
O
5B-10B
5-10: n = 0, 1, 2, 4, 6, 8
Scheme 1. The synthesis of target compounds that are designed to be gelators.
5C-9C
5A-10A
O
O
O
Ph
O
Ph
O
Ph
OCH3
O
O
O
O
O
HO
O
O
O
O
OH
OCH3
OCH3
O
O
NH
O
HN
NH
NH
11A (n = 1)
12A (n = 3)
11B (n = 1)
12B (n = 3)
11C (n = 1)
12C (n = 3)
Figure 3. Structures of carbamate derivatives that are potential hydrogelators.

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G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
contain additional hydrogen bonding sites, which might
also contribute to gelation in water.
The gelation properties of all compounds synthesized
are given in Table 1. All compounds without free hydr-
oxyl groups (5A–12A) are insoluble in water. The
shorter chain diester (5A) formed gels in hexane and
ethanol. The longest chain diester (10A) also formed gels
in ethanol. The dicarbamates are not gelators in the
solvents tested. Compounds with one free hydroxyl
group exhibited versatile gelation properties in hexane
and water but they are soluble in ethanol (Table 1).
Typically the gels in pure water are opaque; an example
is shown in Figure 4a. The reason that these gels are not
transparent is probably due to the partial solubility of
these compounds in pure water. For some samples, par-
tial crystallization also led to opaque gels. In an ethanol/
water mixture, the gels formed by the carbamate 11B are
transparent at low concentrations (Fig. 4b), but translu-
cent at higher concentrations. The gel to solution
transition temperatures were estimated for compounds
5B, 6B, 7B, and 12B in pure water at a concentration
of 10 mg/mL (80–99, 78–93, 84–94, and 99–105 ꢁC,
respectively).
Figure 4. (a) Opaque gels formed by compound 6B in water (10 mg/
mL); (b) clear gels formed by compound 11B in ethanol/water (1:2 v/v,
1.4 mg/mL).
bamates did not form stable gels in pure water. However,
they form stable gels in a mixture of water and polar
organic solvents. Both 11C and 12C are able to gelate
a 1:1 mixture of DMSO/water (v/v) at about 10 mg/
mL. Compound 11B also formed stable transparent gels
in 1:2 (v/v) ethanol water mixture at a concentration of
1.4 mg/mL (Fig. 4b). Compounds 11B and 12B can form
stable opaque gels in a 1:5 mixture of DMSO/water (v/v)
at concentrations of 3 and 4 mg/mL, respectively. Nota-
bly, DMSO is a solvent often used to dissolve water
insoluble drugs to deliver them through skin.
In addition to the results shown in Table 1, the 2-
heptynoic ester 7B also gelates water/alcohol mixtures
and water/DMF mixtures. The carbamate 12B formed
a stable gel in water at 4 mg/mL. Other monochain car-
Optical and electronic microscopy studies showed that
these gelators typically form long fibers, tubules, or
rods. Representative images are shown in Figure 5.
The more effective gelators usually formed very long
fibers that are birefringent. Based on the optical micro-
graphs, the fibers that resulted from the water gels
generally showed crystal-like structures. They polarize
light into a gradient of different colors (Fig. 5e). These
properties indicate some liquid-crystal properties and
confirm that the gels can have localized order in their
packing modes. Some tubules contain nested helices in
their center (Fig. 5h). The scanning electronic micro-
graphs (SEMs) indicated an intertwined fibrous
assembly. We also observed that larger tubules are com-
posed of a bundle of smaller fibers (Fig. 5b and g). These
fibers are potentially useful in forming a functional drug
delivery matrix and in the separation of biological
molecules. The compounds with excellent gelation prop-
erties can be synthesized selectively in high yields by
different methods. Their applications and the detailed
characterization of molecular order will be reported in
the future.
Table 1. Gelation properties of compounds 5A–12C in hexane, water
and ethanola,b
Compound
Hexane
Water
Ethanol
5A
6A
G 5
G 15
P
G 21
S
S
P
P
I
I
I
I
I
I
I
I
G 20
P
P
P
S
G 20
S
S
7A
8A
9A
10A
11A
12A
5B
6B
Gp 10
Gp 10
Gp 5
P
P
P
P
P
G 4
G 7
G 7
Gp 10
P
I
P
G 4
S
S
S
S
S
S
S
S
7B
8B
9B
10B
11B
12B
5C
6C
G 3
G 3
G 3
P
Gp 20
G 4
P
G 7
G 7
G 8
Gp 10
P
S
S
S
S
S
S
S
7C
8C
9C
11C
12C
P
G 17
3. Conclusion
a G, gel at room temperature; Gp, unstable gel; P, precipitation; S,
soluble (ꢀ20 mg/mL).
In summary, we have synthesized and characterized sev-
eral series of methyl a-D-glucopyranoside derivatives.
These compounds were synthesized by a one-pot reac-
b The numbers after the description letter represent the concentrations
for gelation in mg/mL.

G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
709
Figure 5. The scanning electron micrographs (a–d) and optical micrographs (e–h) of dried gels from water (a–f) and hexane (g–h). The numbers
following are concentrations of gelators in mg/mL. (a) 5B, 5; (b) 6B, 10; (c) 7B, 10; (d) 6C, 10; (e) 5B, 5; (f) 7C, 10; (g) 5C, 5; (h) 6C, 5; (e) is obtained
under crossed polarizer and (f)–(h) are bright field images.
tion and separated by chromatography. They are excel-
lent gelators in hexane, ethanol, and water. The short-
chain monoesters that contain 5–7 carbon chains are
versatile gelators for both water and hexane. The hydro-
gen bonding of the free hydroxyl groups with water and
other molecules is important for their self-assembly
properties. The diesters without free hydroxyl groups
cannot form gels in water, but they can form gels in hex-
ane and ethanol. Perhaps p–p stacking among the gela-
tors and hydrophobic interactions of the molecules with
hexane contributed to the gelation properties observed.
The monocarbamates that contain 5–7 carbon chains
are also excellent gelators for water and organic
solvents. The reversible physical gelation in water or
water/DMSO mixture can be useful in applications such
as enzyme immobilization and drug delivery. The corre-
lation between structures and gelation properties of
these molecules may be utilized in designing other effec-
tive hydrogelators. Supramolecular hydrogels formed by
small sugar derivatives can be used in enzyme purifica-
tion, protein and DNA immobilization, and as scaffold-
ing material for tissue engineering.

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G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
4. Experimental
4.2.2. General procedure for the synthesis of compounds
11A–12C. 1.33 equiv of the corresponding isocyanate
was dissolved in CH2Cl2. One equivalent of compound
4 was then added to the stirred isocyanate solution.
Sometimes, a small amount of Et3N (1–2 drops) was
be added to the mixture. After stirring at room temper-
ature for 24–48 h, the solution was concentrated and
purified by chromatography on silica gel with a gradient
solvent system (hexane/acetone from 19:1 to 3:1).
4.1. General methods and materials
4.1.1. Materials and instrumentation. Chemicals were
usually purchased from Aldrich, and VWR; the acetyl-
ene containing fatty acids were purchased from GFS
Chemicals. Optical microscope images were recorded
by Olympus BX60 microscope and CCD camera. The
samples were prepared as thin slices of gels placed on
a cleaned glass slide, the gels were left to air dry to
remove excess solvent. NMR spectra were recorded
using 400–500 MHz Varian NMR spectrometers. IR
data were recorded using Bruker Tensor 27 with direct
sample observation (no KBr pellets). SEM images were
obtained using JEOL Model 5410. Melting points were
measured using Fisher–Jones melting point apparatus,
the melting points are uncorrected.
4.3. Characterization data for new compounds
The following sections detail the characterization of
these compounds, including their melting points, major
1
IR absorptions, H and 13NMR spectroscopy data and
high-resolution mass spectrometry data. The protons
on the sugar headgroup were labeled based on the posi-
tions to which they attached. The isolated yields from
the one-pot reactions are not optimized, and the diol
headgroup and the acid ratio in moles are given for each
4.1.2. Gelation testing. About 3–4 mg of the sample
was placed in a small vial with a cap, 0.1 mL solvent
was initially added to the vial. The mixture was then
heated or sonicated until homogeneous, then left stand-
ing for 15 min. The solubility of these compounds in dif-
ferent solvents are recorded as I (insoluble), S (soluble),
P (cool down crystallized or precipitated), G (stable gel),
and Gp (unstable gel). The vials containing gels were
inverted and when no solvent flowed it was recorded
as G, otherwise as Gp. Serial dilution was performed on
gels to find the minimum gelation concentration (mg/mL).
1
series. In the H NMR data below, the abbreviation
‘app t’ is used to describe the multiplicity of signals cou-
pled to two magnetically inequivalent hydrogens in
which both coupling constants are of the same
magnitude.
4.4. Compounds 5A–C
The diol and acid ratio used was ꢀ1:1, total yield 54.4%.
4.4.1. Methyl 4,6-O-benzylidene-2,3-di-O-(4-pentynoyl)-
a-D-glucopyranoside (5A). White crystals, mp 104.0–
105.8 ꢁC; yield 6.6%; IR (cmÀ1) 3299, 2937, 2869,
2119, 1747, 1371, 1152, 1124, 1098, 1053, 994, 919,
4.2. General synthesis methods
4.2.1. General procedure for the synthesis of compounds
5A–10C. One equivalent of acid was dissolved in anhy-
drous CH2Cl2, and 3 equiv of oxalyl chloride were
added to the solution. The reaction mixture was stirred
under anhydrous conditions for 4–8 h, then was concen-
trated on a rotary evaporator to remove the solvent and
residual oxalyl chloride. The acid chloride thus obtained
was then re-dissolved in anhydrous CH2Cl2, 1 equiv of
methyl 4,6-O-benzylidene-a-D-glucopyranoside was
added to the solution. The mixture was stirred for
5 min, and about 5 equiv of anhydrous pyridine was
added. The reaction mixture was left stirring at room
temperature for 24 h after which the solvent was
removed and the residue was taken up in EtOAc or
CH2Cl2. The organic phase was then washed with 5%
sodium bicarbonate solution once, and water 3–4 times.
The combined organic phase was dried with Na2SO4
overnight. The solvent was removed and the product
mixture was then separated by flash chromatography
using a gradient of solvent systems (hexane/EtOAc).
The three isomers were isolated; the isolated yield of
diester is 10–20%, the O2-monoester is 40–70%, and
the O3-monoester is ꢀ10%.
1
736, 699; H NMR (400 MHz, CDCl3) d 7.38–7.46 (m,
2H, Ar-H), 7.30–7.36 (m, 3H, Ar-H), 5.60 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-3), 5.48 (s, 1H, PhCH), 4.90–4.95
(m, 2H, H-1, H-2), 4.29 (dd, 1H, J5,6e 4.9, J6e,6a
9.8 Hz, H-6eq), 3.91 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a
9.8 Hz, H-5), 3.76 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-
6ax), 3.65 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.39 (s,
3H, OCH3), 2.40–2.63 (m, 8H, 2 · CH2CH2), 1.97 (t,
1H, J 2.9 Hz, CH2C„CH), 1.86 (m, 1H, J 2.9 Hz,
CH2C„CH); 13C NMR (CDCl3, 100 MHz) d 171.0,
170.4, 136.8, 129.0, 128.1, 126.1, 101.4, 97.4, 82.2,
82.0, 79.0, 71.6, 69.2, 69.1, 68.7, 62.2, 55.3, 33.13,
33.07, 14.3, 14.2; HR ESIMS calcd for C24H27O8
[M+H]+ 443.1706, found 443.1710.
4.4.2. Methyl 4,6-O-benzylidene-2-O-(4-pentynoyl)-a-D-
glucopyranoside (5B). White crystals, mp 71.8–73.5 ꢁC;
yield, 35.6%; IR (cmÀ1) 3495, 3287, 2933, 2866, 1743,
1
1379, 1150, 1124, 1094, 1061, 988, 918, 738, 700; H
NMR (400 MHz, CDCl3) d 7.43–7.50 (m, 2H, Ar-H),
7.31–7.37 (m, 3H, Ar-H), 5.53 (s, 1H, PhCH), 4.93 (d,
1H, J1,2 3.9 Hz, H-1), 4.81 (dd, 1H, J1,2 3.9, J2,3

G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
711
9.8 Hz, H-2), 4.27 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 4.18 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 3.83
(dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5), 3.74 (app
t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.56 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-4), 3.37 (s, 3H, OCH3), 2.62 (t,
2H, J = 7.3 Hz, CH2CO), 2.51 (m, 2H, CH2C„CH),
2.30 (s, broad, OH), 2.00 (t, 1H, J 2.9 Hz, CH2C„CH);
13C NMR (CDCl3, 100 MHz) d 171.3, 136.8, 129.1,
128.2, 126.2, 101.8, 97.3, 82.3, 81.1, 73.7, 69.2, 68.6,
68.2, 61.9, 55.2, 33.0, 14.2; HR ESIMS calcd for
C22H33NO7 [M+H]+ 363.1444, found 363.1432.
4.5.2. Methyl 4,6-O-benzylidene-2-O-(5-hexynoyl)-a-D-
glucopyranoside (6B). White crystals; mp 112.6–
113.8 ꢁC; yield 44.0%; IR (cmÀ1) 3505, 3287, 2980,
2910, 1743, 1457, 1383, 1252, 1150, 1125, 1095, 1042,
1
985, 964, 917, 739, 702 and 657; H NMR (400 MHz,
CDCl3) d 7.44–7.52 (m, 2H, 2Ar-H), 7.32–7.39 (m, 3H,
3Ar-H), 5.52 (s, 1H, PhCH), 4.93 (d, 1H, J1,2 3.9 Hz,
H-1), 4.78 (dd, 1H, J1,2 3.9, J2,3 9.8 Hz, H-2), 4.27 (dd,
1H, J5,6e 4.9, J6e,6a 9.8 Hz, H-6eq), 4.14 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-3), 3.81 (dt, 1H, J5,6e 4.9,
J4,5 = J5,6a 9.8 Hz, H-5), 3.73 (app t, 1H, J5,6a = J6e,6a
9.8 Hz, H-6ax), 3.53 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-
4), 3.37 (s, 3H, OCH3), 2.59 (sb, 1H, OH), 2.54 (t, 2H,
J 7.3 Hz, CH2CO), 2.25 (m, 2H, CH2C„CH), 1.96
(m, 1H, CH2C„CH), 1.85 (quintet, 2H, J 7.3 Hz,
CH2CH2CH2); 13C NMR (CDCl3, 100 MHz) d 172.7,
136.9, 129.3, 128.3, 126.3, 102.0, 97.5, 83.1, 81.3,
73.5, 69.2, 68.8, 68.6, 61.9, 55.4, 32.7, 23.5, 17.6; HR
ESIMS calcd for C20H25O7 [M+H]+ 377.1600, found
377.1588.
4.4.3. Methyl 4,6-O-benzylidene-3-O-(4-pentynoyl)-a-D-
glucopyranoside (5C). White crystals, mp 174.0–
175.8 ꢁC; yield 12.2%; IR (cmÀ1) 3566, 3306, 2872,
1746, 1371, 1178, 1122, 1096, 1072, 1058, 1003, 731,
1
669, 651; H NMR (400 MHz, CDCl3) d 7.39–7.44 (m,
2H, Ar-H), 7.30–7.36 (m, 3H Ar-H), 5.47 (s, 1H,
PhCH), 5.33 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 4.79
(d, 1H, J1,2 3.9 Hz, H-1), 4.29 (dd, 1H, J5,6e 4.9, J6e,6a
9.8 Hz, H-6eq), 3.85 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a
9.8 Hz, H-5), 3.73 (app t, 1H, J5,6a = J6e,6a 9.8 Hz,
H-6ax), 3.66 (dd, 1H, J1,2 3.9, J3,4 9.8 Hz, H-2), 3.57
(app t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.45 (s, 3H,
OCH3), 2.62 (t, 2H, J = 7.3 Hz, CH2CO), 2.49 (m, 2H,
CH2C„CH), 1.86 (t, 1H, CH2C„CH), 1.66 (sb, OH);
13C NMR (CDCl3, 100 MHz), d 171.1, 136.9, 129.0,
128.1, 126.2, 101.5, 100.0, 82.3, 78.6, 72.6, 71.7, 69.0,
68.9, 62.7, 55.6, 33.3, 14.4; HR ESIMS calcd for
C22H33NO7 [M+H]+ 363.1444, found 363.1445.
4.5.3. Methyl 4,6-O-benzylidene-3-O-(5-hexynoyl)-a-D-
glucopyranoside (6C). White crystals, mp 138.5–
139.2 ꢁC; yield 9.8%; IR (cmÀ1) 3662, 3466, 3299,
2937, 2842, 2119, 1747, 1371, 1266, 1152, 1124, 1098,
1053, 994, 919, 736, 699, 651; 1H NMR (400 MHz,
CDCl3) d 7.39–7.47 (m, 2H, Ar-H), 7.30–7.38 (m, 3H,
Ar-H), 5.48 (s, 1H, PhCH), 5.32 (app t, 1H, J2,3 = J3,4
9.8 Hz, H-3), 4.79 (d, 1H, J1,2 3.9 Hz, H-1), 4.29 (dd,
1H, J5,6e 4.9, J6e,6a 9.8 Hz, H-6eq), 3.85 (dt, 1H, J5,6e
4.9, J4,5 = J5,6a 9.8 Hz, H-5), 3.73 (app t, 1H,
J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.64 (m, 1H, H-2), 3.57
(app t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.45 (s, 3H,
OCH3), 2.50 (t, 2H, J 7.3 Hz, CH2CO), 2.20 (m, 2H,
CH2C„CH), 1.92 (t, 1H, J 2.9 Hz, CH2C„CH), 1.84
(quintet, 2H, J 7.3 Hz, CH2CH2CH2); 13C NMR
(CDCl3, 100 MHz), d, 173.1, 136.9, 129.1, 128.2, 126.1,
101.5, 100.1, 83.3, 78.6, 72.2, 71.8, 69.0, 68.9, 62.7,
55.6, 33.0, 23.7, 17.6; HR ESIMS calcd for C20H25O7
[M+H]+ 377.1600, found 377.1592.
4.5. Compounds 6A–C
The diol and acid ratio used was ꢀ1:1, total yield 58.4%.
4.5.1. Methyl 4,6-O-benzylidene-2,3-di-O-(5-hexynoyl)-a-
D-glucopyranoside (6A). White crystals, mp 92.1–
94.1 ꢁC; yield 4.6%; IR (cmÀ1) 3307, 3054, 2980, 2888,
2117, 1747, 1458, 1383, 1265, 1149, 1099, 1049, 964,
733, 703, 643; 1H NMR (400 MHz, CDCl3) d 7.39–
7.46 (m, 2H, 2Ar-H), 7.30–7.37 (m, 3H, Ar-3CH), 5.59
(app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 5.49 (s, 1H, PhCH),
4.94 (d, 1H, J1,2 3.9 Hz, H-1), 4.89 (dd, 1H, J1,2 3.9, J2,3
9.8 Hz, H-2), 4.29 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 3.91 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5),
3.76 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.64 (app
t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.39 (s, 3H, OCH3),
2.48 (m, 2H, CH2CO), 2.44 (m, 2H, CH2CO), 2.24 (dt,
2H, J 2.9, 6.8 Hz, CH2C„CH), 2.18 (dt, 2H, J 2.9,
4.6. Compounds 7A–C
The diol and acid ratio used was 1:1, total yield 80.3%.
4.6.1. Methyl 4,6-O-benzylidene-2,3-di-O-(5-heptynoyl)-
a-D-glucopyranoside (7A). White crystals, mp 64.0–
66.0 ꢁC; yield 12.8%; IR (cmÀ1, film) 3305, 3055, 2987,
2940, 2869, 2117 (weak), 1745, 1421, 1266, 1053, 1021,
1
6.8 Hz, CH2C„CH), 1.96 (t, 1H,
J
2.9 Hz,
740, 705; H NMR (400 MHz, CDCl3) d 7.37–7.44 (m,
CH2C„CH), 1.91 (t, 1H, J 2.9 Hz, CH2C„CH), 1.80
(m, 4H, 2 · CH2CH2CH2); 13C NMR (CDCl3,
100 MHz) d 172.4, 171.7, 136.8, 129.0, 128.2, 126.0,
101.5, 97.5, 83.0, 82.9, 79.1, 71.5, 69.3, 69.1, 68.7, 62.2,
55.3, 32.65, 32.56, 23.6, 23.4, 17.6, 17.5; HR ESIMS
calcd for C26H31O8 [M+H]+ 471.2019, found 424.2030.
2H, Ar-H), 7.30–7.36 (m, 3H, Ar-H), 5.59 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-3), 5.48 (s, 1H, PhCH), 4.93 (d,
1H, J1,2 3.9 Hz, H-1), 4.89 (dd, 1H, J1,2 3.9, J2,3
9.8 Hz, H-2), 4.29 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 3.91 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5),
3.75 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.63 (app

712
G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.39 (s, 3H, OCH3), 2.24–
2.42 (m, 4H, 2 · CH2CO), 2.19 (dt, 2H, J 2.9, 6.8 Hz,
CH2C„CH), 2.09 (dt, 2H, J 2.9, 6.8 Hz, CH2C„CH)
1.93 (t, 1H, J 2.9 Hz, CH2C„CH), 1.89 (t, 1H, J
2.9 Hz, CH2C„CH), 1.70 (m, 4H, CH2CH2CO), 1.42–
1.58 (m, 4H, CH2CH2C„CH); 13C NMR (CDCl3,
100 MHz) d 172.7, 172.1, 136.8, 129.0, 128.2, 126.1,
101.5, 97.6, 83.8, 83.7, 79.2, 71.4, 68.8, 68.7, 68.6, 62.3,
55.4, 33.7, 33.5, 27.7, 27.5, 24.0, 23.9, 18.1, 18.0; HR
ESIMS calcd for C28H35O8 [M+H]+ 499.2332, found
499.2320.
4.7.1. Methyl 4,6-O-benzylidene-2,3-di-O-(8-nonynoyl)-a-
D-glucopyranoside (8A). White crystals, mp 63.8–
65.0 ꢁC; yield 9.6%; IR (cmÀ1) 3307, 2937, 2862, 2115,
1745, 1458, 1266, 1151, 1126, 1095, 1051, 1021, 988,
916, 735, 699, 632; 1H NMR (400 MHz, CDCl3) d
7.38–7.44 (m, 2H, Ar-H), 7.30–7.36 (m, 3H, Ar-H),
5.58 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 5.48 (s, 1H,
PhCH), 4.92 (d, 1H, J1,2 3.9 Hz, H-1), 4.88 (dd, 1H,
J1,2 3.9, J2,3 9.8 Hz, H-2), 4.28 (dd, 1H, J5,6e 4.9, J6e,6a
9.8 Hz, H-6eq), 3.91 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a
9.8 Hz, H-5), 3.75 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-
6ax), 3.62 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.39 (s,
3H, OCH3), 2.22–2.40 (m, 4H, 2 · CH2CO), 2.16 (m,
2H, CH2C„CH), 2.09 (m, 2H, CH2C„CH), 1.89–
1.94 (m, 2H, 2 · CH2C„CH), 1.46–1.65 (m, 8H,
2 · CH2CH2CO, 2 · CH2CH2C„CH), 1.20–1.45 (m,
8H, 2 · CH2CH2CH2CH2CO); 13C NMR (CDCl3,
100 MHz) d 173.0, 172.3, 136.8, 129.0, 128.1, 126.0,
101.4, 97.6, 84.4, 84.3, 79.2, 71.3, 68.8, 68.6, 68.24,
68.18, 62.2, 55.3, 34.1, 33.9, 28.4, 28.3, 28.2, 28.1, 28.0,
24.8, 24.6, 18.2; HR ESIMS calcd for C32H43O8
[M+H]+ 555.2958, found 555.2957.
4.6.2. Methyl 4,6-O-benzylidene-2-O-(6-heptynoyl)-a-D-
glucopyranoside (7B). White crystals, mp 58.0–59.0 ꢁC;
yield 48.9%; IR (cmÀ1, film) 3596, 3305, 3055, 2987,
2938, 2869, 1739, 1421, 1266, 1059, 1039, 896, 740,
1
705; H NMR (400 MHz, CDCl3) d 7.44–7.50 (m, 2H,
Ar-H), 7.32–7.39 (m, 3H, Ar-H), 5.52 (s, 1H, PhCH),
4.93 (d, 1H, J1,2 3.9 Hz, H-1), 4.78 (dd, 1H, J1,2 3.9,
J2,3 9.8 Hz, H-2), 4.27 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 4.14 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 3.82
(dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5), 3.73 (app t,
1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.55 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-4), 3.37 (s, 3H, OCH3), 2.41 (t,
2H, J 7.3 Hz CH2CO), 2.19 (dt, 2H, J 2.9, 7.3 Hz,
CH2CH2C„CH), 1.94 (t, 1H, J 2.9 Hz, CH2C„CH),
1.74 (quintet, 2H, J 7.3 Hz, CH2CH2CO), 1.56 (m, 2H,
J 7.3, CH2CH2C„CH); 13C NMR (CDCl3, 100 MHz)
d 173.1, 136.9, 129.3, 128.3, 126.2, 102.0, 97.5, 83.9,
81.3, 73.4, 68.8, 68.7, 68.6, 61.9, 55.4, 33.5, 27.6, 23.9,
18.0; HR ESIMS calcd for C21H27O7 [M+H]+
391.1757, found 391.1763.
4.7.2. Methyl (R)-4,6-O-benzylidene-2-O-(8-nonynoyl)-a-
D-glucopyranoside (8B). White crystals, mp 80.5–
82.4 ꢁC; yield 38.4%; IR (cmÀ1) 3505, 3286, 2935,
2862, 1743, 1458, 1257, 1210, 1125, 1094, 1061, 1042,
1
986, 965, 916, 764, 745, 700, 674; H NMR (CDCl3,
400 MHz) d 7.44–7.52 (m, 2H, Ar-H), 7.32–7.40 (m,
3H, Ar-H), 5.52 (s, 1H, PhCH), 4.93 (d, 1H, J1,2
3.9 Hz, H-1), 4.78 (dd, 1H, J1,2 3.9, J2,3 9.8 Hz, H-2),
4.27 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz, H-6eq), 4.15 (app
t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 3.82 (dt, 1H, J5,6e 4.9,
J4,5 = J5,6a 9.8 Hz, H-5), 3.73 (app t, 1H, J5,6a = J6e,6a
9.8 Hz, H-6ax), 3.53 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-
4), 3.37 (s, 3H, OCH3), 2.39 (t, 2H, J 7.8 Hz, CH2CO),
2.16 (dt, 2H, J 2.9, 6.8 Hz, CH2C„CH), 1.92 (t, 1H, J
2.9 Hz, CH2C„CH), 1.64 (m, 2H, CH2CH2CO), 1.50
(m, 2H, CH2CH2C„CH), 1.38–1.44 (m, 4H,
CH2CH2CH2CH2CO); 13C NMR (CDCl3, 100 MHz) d
173.1, 136.8, 128.9, 128.0, 126.1, 101.6, 97.3, 84.2,
81.1, 73.2, 68.5, 68.2, 61.8, 60.1, 55.1, 33.7, 28.1, 28.0,
24.5, 18.0; HR ESIMS calcd for C23H31O7 [M+H]+
419.2070, found 419.2046.
4.6.3. Methyl 4,6-O-benzylidene-3-O-(6-heptynoyl)-a-D-
glucopyranoside (7C). White crystals, mp 124.0–
125.0 ꢁC; yield 18.6%; IR (cmÀ1, film) 3305, 3054,
1
2987, 1741, 1422, 1266, 1057, 896, 740, 705; H NMR
(400 MHz, CDCl3) d 7.30–7.44 (m, 5H, Ar-H), 5.47 (s,
1H, PhCH), 5.32 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3),
4.78 (d, 1H, J1,2 3.9 Hz, H-1), 4.28 (dd, 1H, J5,6e 4.9,
J6e,6a 9.8 Hz, H-6eq), 3.85 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a
9.8 Hz, H-5), 3.73 (app t, 1H, J5,6a = J6e,6a 9.8 Hz,
H-6ax), 3.64 (m, 1H, H-2), 3.57 (app t, 1H, J2,3 = J3,4
9.8 Hz, H-4), 3.45 (s, 3H, OCH3), 2.39 (t, 2H, J
7.3 Hz, CH2CO), 2.11 (dt, 2H,
J 2.9, 6.8 Hz,
CH2CH2C„CH), 1.89 (t, 1H, J 2.9 Hz, CH2C„CH),
1.74 (quintet, 2H, J 7.3, CH2CH2CO), 1.51 (quintet,
2H, J 6.8 Hz, CH2CH2C„CH); 13C NMR (CDCl3,
100 MHz) d 173.5, 136.9, 129.1, 128.2, 126.1, 101.5,
100.1, 84.0, 78.7, 72.1, 71.8, 68.9, 68.5, 62.7, 55.6, 33.8,
27.5, 24.0, 18.0; HR ESIMS calcd for C21H27O7
[M+H]+ 391.1757, found 391.1751.
4.7.3. Methyl 4,6-O-benzylidene-3-O-(8-nonynoyl)-a-D-
glucopyranoside (8C). White crystals, mp 97.6–99.0;
yield 15.2%; IR (cmÀ1) 3565, 3308, 2938, 2305, 1745,
1458, 1265, 1132, 1096, 1070, 1016, 984, 896, 734, 703;
1H NMR (CDCl3, 400 MHz) d 7.38–7.46 (m, 2H, Ar-
H), 7.28–7.37 (m, 3H, Ar-H), 5.46 (s, 1H, s, 1H, PhCH),
5.31 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 4.78 (d, 1H, J1,2
3.9 Hz, H-1), 4.27 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 3.84 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5),
3.72 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.64 (dd,
1H, J1,2 3.9, J2,3 9.8 Hz, H-2), 3.55 (app t, 1H,
4.7. Compounds 8A–C
The diol and acid ratio used was 1:1, yield 63.2%.

G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
713
J2,3 = J3,4 9.8 Hz, H-4), 3.43 (s, 3H, OCH3), 2.35 (t, 2H,
J 7.3 Hz, CH2CO), 2.08 (dt, 1H, J 2.9, 6.8 Hz,
CH2C„CH), 1.91 (t, 1H, J 2.9 Hz, CH2C„CH), 1.61
(m, 2H, CH2CH2CO), 1.40 (m, 2H, CH2CH2C„CH),
1.22–1.35 (m, 4H, CH2CH2CH2CH2CO); 13C NMR
(CDCl3, 100 MHz) d 173.6, 136.9, 128.9, 128.1, 126.0,
101.3, 100.1, 84.5, 78.6, 71.9, 71.7, 68.8, 68.2, 62.6,
55.5, 34.2, 28.2, 28.0, 24.8, 18.2; HR ESIMS calcd for
C23H31O7 [M+H]+ 419.2070, found 419.2065.
29.0, 28.8, 28.6, 28.3, 24.8, 18.3; HR ESIMS Calcd for
C25H35O7 [M+H]+ 447.2383, found 447.2369.
4.8.3. Methyl 4,6-O-benzylidene-3-O-(10-undecynoyl)-a-
D-glucopyranoside (9C). Off white solid, mp 93.8–
95.0 ꢁC; yield 10.5%; IR (cmÀ1) 3466, 3299, 2937,
2119, 1747, 1371, 1266, 1152, 1124, 1098, 1053, 994,
919, 736, 699, 651; 1H NMR (CDCl3, 400 MHz) d
7.39–7.45 (m, 2H, Ar-H), 7.30–7.35 (m, 3H, Ar-H),
5.47 (s, 1H, s, 1H, PhCH), 5.31 (app t, 1H, J2,3 = J3,4
9.8 Hz, H-3), 4.78 (d, 1H, J1,2 3.9 Hz, H-1), 4.28 (dd,
1H, J5,6e 4.9, J6e,6a 9.8 Hz, H-6eq), 3.85 (app t, 1H,
J5,6e 4.9, J4,5 9.8, J5,6a 10.7 Hz, H-5), 3.73 (app t, 1H,
J5,6a 10.7, J6e,6a 9.8 Hz, H-6ax), 3.64 (dd, 1H, J1,2 3.9,
J2,3 9.8 Hz, H-2), 3.56 (app t, 1H, J2,3 = J3,4 9.8 Hz,
H-4), 3.45 (s, 3H, OCH3), 2.35 (t, 2H, J 7.8 Hz,
CH2CO), 2.13 (dt, 1H, J 2.9, 6.8 Hz, CH2C„CH),
1.91 (t, 1H, J 2.9 Hz, CH2C„CH), 1.60 (m, 2H,
CH2CH2CO), 1.46 (m, 2H, CH2CH2C„CH), 1.12–
1.36 (m, 8H, (CH2)4CH2CH2CO); 13C NMR (CDCl3,
100 MHz) d 173.9, 137.0, 129.0, 128.2, 126.1, 101.4,
100.1, 84.7, 78.7, 72.0, 71.8, 68.9, 68.1, 62.7, 55.6, 34.3,
29.0, 28.8, 28.6, 28.4, 25.0, 18.3; HR ESIMS calcd for
C25H35O7 [M+H]+ 447.2383, found 447.2398.
4.8. Compounds 9A–C
The diol and acid ratio used was 1:1, total yield 80.3%.
4.8.1. Methyl 4,6-O-benzylidene-2,3-di-O-(10-undecy-
noyl)-a-D-glucopyranoside (9A). White solid, mp
43.0–44.9 ꢁC; yield 14.3%; IR (cmÀ1) 3289, 2931, 2857,
2115, 1746, 1138, 1458, 1378, 1312, 1260, 1151, 1125,
1
1096, 917, 738, 698, 630; H NMR (400 MHz, CDCl3)
d 7.38–7.46 (m, 2H, Ar-H), 7.29–7.35 (m, 3H, Ar-H),
5.58 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 5.48 (s, 1H,
PhCH), 4.92 (d, 1H, J1,2 3.9 Hz, H-1), 4.88 (dd, 1H,
J1,2 3.9, J2,3 9.8 Hz, H-2), 4.28 (dd, 1H, J5,6e 4.9, J6e,6a
9.8 Hz, H-6eq), 3.90 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a
9.8 Hz, H-5), 3.75 (app t, 1H, J5,6a = J6e,6a 9.8 Hz,
H-6ax), 3.62 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.38
(s, 3H, OCH3), 2.18–2.37 (m, 4H, 2 · CH2CO), 2.09–
2.18 (m, 4H, 2 · CH2C„CH), 1.89–1.92 (m, 2H, 2 ·
CH2C„CH), 1.40–1.62 (m, 8H, 2 · CH2CH2CO,
2 · CH2CH2C„CH), 1.10–1.40 (m, 16H, 2 · (CH2)4-
CH2CH2CO); 13C NMR (CDCl3, 100 MHz) d 173.1,
172.4, 136.9, 129.0, 128.1, 126.0, 101.4, 97.6, 84.6,
79.3, 71.3, 68.8, 68.5, 68.1, 62.3, 55.3, 34.2, 34.0, 29.0,
28.9, 28.82, 28.77, 28.6, 28.3, 25.0, 24.8, 18.3; HR
ESIMS calcd for C36H51O8 [M+H]+ 611.3584, found
611.3581.
4.9. Compounds 10A–C
The diol and acid ratio used was 2:1, isomer C was not
isolated, total yield 73.8%.
4.9.1. Methyl 4,6-O-benzylidene-2,3-di-O-(12-tridecy-
noyl)-a-D-glucopyranoside (10A). White solid, mp
49.9–51.8 ꢁC; yield 58.7%; IR (cmÀ1) 3305, 2926, 2856,
2115, 1744, 1367, 1183, 1124, 1097, 1054, 870, 742,
1
631; H NMR (400 MHz, CDCl3) d 7.38–7.46 (m, 2H,
Ar-H), 7.29–7.37 (m, 3H, Ar-H), 5.58 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-3), 5.48 (s, 1H, PhCH), 4.92 (d,
1H, J1,2 3.9 Hz, H-1), 4.88 (dd, 1H, J1,2 3.9, J2,3
9.8 Hz, H-2), 4.28 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 3.91 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5),
3.75 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.62 (app
t, 1H, J2,3 = J3,4 9.8 Hz, H-4), 3.38 (s, 3H, OCH3),
2.28 (m, 4H, 2 · CH2CO), 2.15 (m, 4H, 2 · CH2C„
CH), 1.89–2.02 (m, 2H, 2 · CH2C„CH), 1.42–1.64
(m, 8H, 2 · CH2CH2CO, 2 · CH2CH2C„ CH), 1.02–
1.42 (m, 24H, 2 · (CH2)6CH2CH2CO); 13C NMR
(CDCl3, 100 MHz) d 173.2, 172.4, 136.9, 129.0, 128.1,
126.0, 101.4, 97.6, 84.7, 79.3, 71.3, 68.8, 68.5, 68.0,
62.3, 55.3, 34.2, 34.0, 29.4(m), 29.2, 29.0(m), 28.7,
28.4, 25.0, 24.8, 18.3; HR ESIMS calcd for C40H59O8
[M+H]+ 667.4210, found 667.4203.
4.8.2. Methyl 4,6-O-benzylidene-2-O-(10-undecynoyl)-a-
D-glucopyranoside (9B). White solid, mp 71.0–73.5 ꢁC;
yield 55.5%; IR (cmÀ1) 3522, 3308, 2934, 2859, 2115,
1743, 1458, 1381, 1314, 1266, 1150, 1123, 1093, 1059,
1041, 987, 917, 735, 701, 639; 1H NMR (CDCl3,
400 MHz) d 7.44–7.52 (m, 2H, Ar-H), 7.32–7.40 (m,
3H, Ar-H), 5.54 (s, 1H, PhCH), 4.94 (d, 1H, J1,2
3.9 Hz, H-1), 4.79 (dd, 1H, J1,2 3.9, J2,3 9.8 Hz, H-2),
4.28 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz, H-6eq), 4.17 (app
t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 3.83 (dt, 1H, J5,6e 4.9,
J4,5 = J5,6a 9.8 Hz, H-5), 3.75 (app t, 1H, J5,6a = J6e,6a
9.8 Hz, H-6ax), 3.55 (app t, 1H, J2,3 = J3,4 9.8 Hz,
H-4), 3.38 (s, 3H, OCH3), 2.39 (t, 2H, J 7.8 Hz,
CH2CO), 2.16 (dt, 2H, J 2.9, 6.8 Hz, CH2C„CH),
1.91 (t, 1H, J 2.9 Hz, CH2C„CH), 1.63 (m, 2H,
CH2CH2CO), 1.49 (m, 2H, CH2CH2C„CH), 1.18–
1.42 (m, 8H, (CH2)4CH2CH2CO); 13C NMR (CDCl3,
100 MHz) d, 173.5, 136.9, 129.3, 128.3, 126.3, 102.0,
97.6, 84.7, 81.4, 73.3, 68.8, 68.6, 68.1, 61.9, 55.4, 34.0,
4.9.2. Methyl 4,6-O-benzylidene-2-O-(12-tridecynoyl)-a-
D-glucopyranoside (10B). White crystals, mp 77.0–
78.0 ꢁC; yield 15.1%; IR (cmÀ1) 3478, 3305, 2929,
2856, 2115, 1737, 1376, 1174, 1122, 1094, 1058, 872,

714
G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
1
743, 634; H NMR (CDCl3, 400 MHz) d 7.44–7.52 (m,
2H, Ar-H), 7.32–7.40 (m, 3H, Ar-H), 5.53 (s, 1H,
PhCH), 4.94 (d, 1H, J1,2 3.9 Hz, H-1), 4.78 (dd, 1H,
J1,2 3.9, J2,3 9.8 Hz, H-2), 4.28 (dd, 1H, J5,6e 4.9, J6e,6a
9.8 Hz, H-6eq), 4.16 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-
3), 3.83 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5), 3.75
(app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.55 (app t,
1H, J2,3 = J3,4 9.8 Hz, H-4), 3.38 (s, 3H, OCH3), 2.38
(t, 2H, J 7.8 Hz, CH2CO), 2.15 (dt, 2H, J 2.9, 6.8 Hz,
CH2C„CH), 1.91 (t, 1H, J 2.9 Hz, CH2C„CH), 1.62
(m, 2H, CH2CH2CO), 1.49 (m, 2H, CH2CH2C„CH),
1.12–1.40 (m, 12H, (CH2)6CH2CH2CO); 13C NMR
(CDCl3, 100 MHz) d, 173.6, 136.9, 129.3, 128.3, 126.3,
102.0, 97.6, 84.7, 81.4, 73.4, 68.8, 68.6, 68.0, 62.0,
55.4, 34.1, 29.3, 29.2, 20.0, 28.7, 28.4, 24.9, 18.3; HR
ESIMS calcd for C27H39O7 [M+H]+ 475.2696, found
475.2695.
H-5), 3.75 (app t, 1H, J5,6a = J6e,6a 9.8 Hz, H-6ax), 3.56
(app t, 1H, J2,3, J3,4 9.8 Hz, H-4), 3.41 (s, 3H, OCH3),
3.16 (quartet, 2H, J 6.8, CH2NH), 1.56 (br s, 1H,
OH), 1.49 (quintet, 2H, J 6.8 Hz, CH2CH2NH), 1.23–
1.33 (m, 4H, CH2CH2CH2CH3), 0.88 (t, 3H, J 6.8,
CH2CH3); 13C NMR (CDCl3, 100 MHz) d 155.8,
136.9, 129.0, 128.1, 126.2, 126.1, 101.8, 98.1, 73.9,
68.6, 68.4, 62.0, 55.1, 40.9, 31.6, 30.0, 29.5, 28.8, 28.7,
26.7, 26.5, 22.4, 13.9; HR ESIMS calcd for C20H30-
NO7 [M+H]+ 396.2022, found 396.2014.
4.10.3. Methyl 4,6-O-benzylidene-3-O-(pentyl-carbamoyl)-
a-D-glucopyranoside (11C). White solid, mp 183.0–
185.0 ꢁC; yield 27.6%; IR (cmÀ1, film) 3448, 3054,
2987, 2929, 1725, 1422, 1266, 896, 739, 705; 1H
NMR (400 MHz, CDCl3) d 7.43–7.46 (m, 2H, 2Ar-H),
7.32–7.36 (m, 3H, 3Ar-H), 5.47 (s, 1H, Ph-acetal-CH),
5.13 (app t, 1H, J2,3 = J3,4 9.8 Hz, H-3), 4.70–4.85 (m,
2H, H-2, NH), 4.28 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 3.86 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5),
3.73 (app t, 1H, J5,6a, J6e,6a 9.8 Hz, H-6ax), 3.63 (m,
1H, H-2), 3.54 (app t, 1H, J2,3, J3,4 9.8 Hz, H-4), 3.44
(s, 3H, OCH3), 3.15 (quartet, 2H, J 6.8, CH2NH), 1.47
(quintet, 2H, J 6.8 Hz, CH2CH2NH), 1.22–1.30 (m,
4H, m, 4H, CH2CH2CH2CH3), 0.85 (t, 3H, J 6.8,
CH2CH3). 13C NMR (CDCl3, 100 MHz) d 156.7,
137.0, 129.0, 128.1, 126.2, 101.5, 100.3, 78.7, 73.1,
72.2, 68.9, 62.6, 55.5, 41.1, 29.3, 28.7, 22.2, 13.8; HR
ESIMS calcd for C20H30NO7 [M+H]+ 396.2022, found
396.2014.
4.10. Compounds 11A–C
The diol and isocyanoate ratio used was 3:4, total yield
97.9%.
4.10.1. Methyl 4,6-O-benzylidene-2,3-di-O-(pentyl-car-
bamoyl)-a-D-glucopyranoside (11A). Semisolid; yield
10.7%; IR (cmÀ1, film) 3444, 3055, 2987, 2934, 1731,
1519, 1422, 1266, 1053, 896, 731 and 706; 1H NMR
(400 MHz, CDCl3) d 7.42–7.45 (m, 2H, 2Ar-H), 7.30–
7.34 (m, 3H, 3Ar-H), 5.48 (s, 1H, PhCH), 5.37 (app t,
1H, J2,3 = J3,4 9.8 Hz, H-3), 4.95 (m, 1H, NH), 4.91
(d, 1H, J1,2 3.9 Hz, H-1), 4.78 (dd, 1H, J1,2 3.9, J2,3
9.8 Hz, H-2), 4.67 (m, 1H, NH), 4.27 (dd, 1H, J5,6e
4.9, J6e,6a 10.7 Hz, H-6eq), 3.89 (dt, 1H, J5,6e 4.9,
J4,5 = J5,6a 9.8 Hz, H-5), 3.75 (app t, 1H, J5,6a 9.8,
J6e,6a 10.7 Hz, H-6ax), 3.59 (app t, 1H, J2,3 = J3,4
9.8 Hz, H-4), 3.39 (s, 3H, OCH3), 3.06–3.16 (m, 4H,
2 · CH2NH), 1.44 (m, 4H, 2 · CH2CH2NH), 1.26–1.30
(m, 4H, CH2CH2CH2CH3), 1.22–1.26 (m, 4H,
CH2CH2CH2CH3), 0.87 (t, 3H, J 6.8, CH2CH3), 0.83
(t, 3H, J 6.8, CH2CH3); 13C NMR (CDCl3, 100 MHz)
d 155.5, 155.4, 136.9, 128.9, 128.0, 126.1, 101.4, 98.3,
71.9, 69.9, 68.8, 62.3, 55.2, 41.0, 40.4, 29.9, 29.4, 28.9,
28.7, 22.3, 22.1, 13.8; HR ESIMS calcd for
C26H41N2O8 [M+H]+ 509.2863, found 509.2850.
4.11. Compounds 12A–C
The diol and isocyanate ratio used was 3:4, total yield
71.5%.
4.11.1. Methyl 4,6-O-benzylidene-2,3-di-O-(heptyl-car-
bamoyl)-a-D-glucopyranoside (12A). White amorphous
solid, mp 98.5–101.0 ꢁC; yield 5.1%; IR (cmÀ1) 3443,
2929, 2859, 2360, 2341, 1732, 1519, 1374, 1185, 1097,
1
1053, 745, 669; H NMR (CDCl3, 400 MHz) 7.43–7.46
(m, 2H, 2Ar-H), 7.30–7.34 (m, 3H, 3Ar-H), 5.48 (s,
1H, Ph-acetal-CH), 5.37 (app t, 1H, J2,3 = J3,4 9.8 Hz,
H-3), 4.95 (m, 1H, NH), 4.91 (d, 1H, J1,2 3.9 Hz, H-1),
4.79 (dd, 1H, J1,2 3.9, J2,3 9.8 Hz, H-2), 4.67 (t, J
4.9 Hz, 1H, NH), 4.27 (dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz,
H-6eq), 3.90 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz, H-5),
3.75 (app t, 1H, J5,6a, J6e,6a 9.8 Hz, H-6ax), 3.59 (app t,
1H, J2,3, J3,4 9.8 Hz, H-4), 3.39 (s, 3H, OCH3),
3.07–3.16 (m, 4H, 2 · CH2NH), 1.43 (m, 4H,
2 · CH2CH2NH), 1.20–1.28 (m, 16H, 2 · (CH2)4CH3),
0.85 (m, 6H, 2 · CH2CH3); 13C NMR (CDCl3,
100 MHz) d 155. 5, 155.4, 137.0, 128.9, 128.1, 126.2,
101.4, 98.3, 79.4, 75.5, 72.0, 69.9, 68.8, 62.3, 55.2, 45.8,
41.1, 40.5, 31.7, 31.6, 30.3, 29.8, 29.7, 29.4, 29.0, 28.9,
4.10.2. Methyl 4,6-O-benzylidene-2-O-(pentyl-carbamoyl)-a-
D-glucopyranoside (11B). White needles, mp 147.5–
148.5 ꢁC; yield 59.6%; IR (cmÀ1, film) 3442, 3055,
2987, 2935, 2872, 1726, 1518, 1266, 1094, 993, 740,
1
705; H NMR (400 MHz, CDCl3) d 7.46–7.49 (m, 2H,
2Ar-H), 7.33–7.37 (m, 3H, 3Ar-H), 5.54 (s, 1H, PhCH),
4.96 (d, 1H, J1,2 3.9 Hz, H-1), 4.91 (m, 1H, CONH), 4.71
(dd, 1H, J1,2 3.9, J2,3 9.8 Hz, H-2), 4.28 (dd, 1H, J5,6e
4.9, J6e,6a 9.8 Hz, H-6eq), 4.12 (app t, 1H, J2,3 = J3,4
9.8 Hz, H-3), 3.82 (dt, 1H, J5,6e 4.9, J4,5 = J5,6a 9.8 Hz,

G. Wang et al. / Carbohydrate Research 341 (2006) 705–716
715
26.8, 26.6, 22.5, 14.0; HR ESIMS calcd for C30H49N2O8
Supplementary data
[M+H]+ 565.3489, found 565.3494.
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
2006.01.023.
4.11.2. Methyl 4,6-O-benzylidene-2-O-(heptyl-carbamoyl)-
a-D-glucopyranoside (12B). Needle-like crystals, mp
131.6–133.0 ꢁC; yield 43.0%; IR (cmÀ1) 3437, 2929,
2658, 2360, 2481, 1723, 1519, 1376, 1093, 1058, 99.4,
1
References
874, 743, 697; H NMR (CDCl3, 400 MHz) 7.47–7.50
(m, 2H, 2Ar-H), 7.34–7.38 (m, 3H, 3Ar-H), 5.54 (s, 1H,
Ph-acetal-CH), 4.95 (d, 1H, J1,2 3.9 Hz, H-1), 4.89 (m,
1H, NH), 4.71 (dd, 1H, J1,2 3.9, J2,3 9.8 Hz, H-2), 4.28
(dd, 1H, J5,6e 4.9, J6e,6a 9.8 Hz, H-6eq), 4.12 (app t, 1H,
J2,3 = J3,4 9.8 Hz, H-3), 3.83 (m, 1H, H-5), 3.75 (app t,
1H, J5,6a, J6e,6a 9.8 Hz, H-6ax), 3.56 (app t, 1H, J2,3, J3,4
9.8 Hz, H-4), 3.41 (s, 3H, OCH3), 3.17 (quartet, 2H, J
6.8 Hz, CH2NH), 1.48 (m, 2H, CH2CH2NH), 1.20–
1.28 (m, 8H, (CH2)4CH3), 0.86 (t, J 6.8 Hz, 3H,
CH2CH3); 13C NMR (CDCl3, 400 MHz) d 155.8, 137.0,
129.2, 128.2, 126.3, 101.9, 98.1, 81.3, 73.9, 68.7,
62.0, 55.2, 41.1, 31.6, 29.6, 28.8, 26.6, 22.5, 14.0; HR
ESIMS calcd for C22H33NO7 [M+H]+ 424.2335, found
424.2331.
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a-D-glucopyranoside (12C). White crystals, mp 181.5–
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1
918, 873. H NMR (CDCl3, 400 MHz) 7.41–7.47 (m,
2H, 2Ar-H), 7.31–7.37 (m, 3H, 3Ar-H), 5.47 (s, 1H,
Ph-acetal-CH), 5.13 (app t, 1H, J2,3 = J3,4 9.8 Hz,
H-3), 4.73–4.83 (m, 2H, H-2, NH), 4.28 (dd, 1H, J5,6e
4.9, J6e,6a 9.8 Hz, H-6eq), 3.85 (dt, 1H, J5,6e 4.9, J4,5
=
J5,6a 9.8 Hz, H-5), 3.72 (app t, 1H, J5,6a, J6e,6a 9.8 Hz,
H-6ax), 3.63 (m, 1H, H-2), 3.54 (app t, 1H, J2,3, J3,4
9.8 Hz, H-4), 3.44 (s, 3H, OCH3), 3.15 (quartet, 2H,
J 6.8, CH2NH), 1.47 (quintet, 2H, J 6.8 Hz, CH2-
CH2NH), 1.22–1.30 (m, 8H, (CH2)4CH3), 0.85 (t, 3H,
J 6.8, CH2CH3); 13C NMR (CDCl3, 100 MHz) d
156.7, 137.0, 129.0, 128.1, 126.2, 101.6, 100.3, 78.8,
77.3, 76.6, 73.2, 72.2, 68.9, 62.6, 55.5, 41.1, 31.6,
29.7, 28.8, 26.6, 22.5, 14.0; HR ESIMS calcd for
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Acknowledgements
We thank for the financial support provided by Univer-
sity of New Orleans start-up fund and NSF grant
518283. Special thanks to the Chemistry Department
at Louisiana State University for providing laboratory
space for us to complete the manuscript submission.
We thank Dr. Steven Mullen at Mass Spectrometry
Facility of UIUC for his assistance, and Dr. Weilie
Zhou from AMRI at UNO with SEM for his
assistance.
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