Synthesis of new glycopolymers containing β-d-mannopyranose, and c-2-substituted β-d-mannopyranose residues as a new class of inhibitor

Article abstract of DOI:10.1081/CAR-100103953

New styryl monomers containing β-D-mannopyranose, 2-acetamido-2-deoxy-β-D-mannopyranose, 2-deoxy-2-fluoro-β-D-mannopyranose, and 2-deoxy-β-D-arabino-hexopyranose on their side chains, were efficiently synthesized as a new class of a potent inhibitor resistant to exo-α-mannosidase digestion. The binding affinity of the carbohydrate polymers obtained from those mannopyranosyl styryl monomers by radical polymerization with Concanavalin A were evaluated. A binding assay indicated that the multivalency effect and the affinity enhancement attained by modification at the C-2 position of the β-D-mannopyranoside residue resulted in the.

Full text of DOI:10.1081/CAR-100103953

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SYNTHESIS OF NEW GLYCOPOLYMERS CONTAINING
β-D-MANNOPYRANOSE, AND C-2-SUBSTITUTED β-
D-MANNOPYRANOSE RESIDUES AS A NEW CLASS OF
INHIBITOR
Shoji Akai a , Yasuhiro Kajihara b , Yasuhiko Nagashima a , Masugu Kamei c , Junko Arai c ,
Masami Bito c & Ken-ichi Sato d
a Laboratory of Organic Chemistry, Faculty of Engineering , Kanagawa University ,
3-27-1, Rokkakubashi, Kanagawa-ku, Yokohama, 221-8686, Japan
b Department of System Functions, Faculty of Science , Yokohama City University , 22-2,
Seto, Kanazawa-ku, Yokohama, 236-0027, Japan
c Sugiyama Chemical & Industrial Laboratory , 11, Kagetori-cho, Totsuka-ku, Yokohama,
245-0046, Japan
d Laboratory of Organic Chemistry, Faculty of Engineering , Kanagawa University ,
3-27-1, Rokkakubashi, Kanagawa-ku, Yokohama, 221-8686, Japan
Published online: 16 Aug 2006.
To cite this article: Shoji Akai , Yasuhiro Kajihara , Yasuhiko Nagashima , Masugu Kamei , Junko Arai , Masami Bito &
Ken-ichi Sato (2001) SYNTHESIS OF NEW GLYCOPOLYMERS CONTAINING β-D-MANNOPYRANOSE, AND C-2-SUBSTITUTED β-
D-MANNOPYRANOSE RESIDUES AS A NEW CLASS OF INHIBITOR, Journal of Carbohydrate Chemistry, 20:2, 121-143, DOI:
10.1081/CAR-100103953
To link to this article: http://dx.doi.org/10.1081/CAR-100103953
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J. CARBOHYDRATE CHEMISTRY, 20(2), 121–143 (2001)
SYNTHESIS OF NEW GLYCOPOLYMERS
CONTAINING ꢀ-D-MANNOPYRANOSE, AND
C-2-SUBSTITUTED ꢀ-D-MANNOPYRANOSE
RESIDUES AS A NEW CLASS OF INHIBITOR
Shoji Akai,1 Yasuhiro Kajihara,2 Yasuhiko Nagashima,1
Masugu Kamei,3 Junko Arai,3 Masami Bito,3 and Ken-ichi Sato1,*
1Laboratory of Organic Chemistry, Faculty of Engineering,
Kanagawa University, 3-27-1, Rokkakubashi, Kanagawa-ku,
Yokohama, 221-8686 Japan
2Department of System Functions, Faculty of Science,
Yokohama City University, 22-2, Seto, Kanazawa-ku,
Yokohama, 236-0027 Japan,
3Sugiyama Chemical & Industrial Laboratory, 11, Kagetori-cho,
Totsuka-ku, Yokohama, 245-0046 Japan
ABSTRACT
New styryl monomers containing ꢀ-D-mannopyranose, 2-acetamido-2-deoxy-
ꢀ-D-mannopyranose, 2-deoxy-2-fluoro-ꢀ-D-mannopyranose, and 2-deoxy-ꢀ-
D-arabino-hexopyranose on their side chains, were efficiently synthesized as a
new class of a potent inhibitor resistant to exo-ꢁ-mannosidase digestion. The
binding affinity of the carbohydrate polymers obtained from those mannopy-
ranosyl styryl monomers by radical polymerization with Concanavalin A were
evaluated. A binding assay indicated that the multivalency effect and the affin-
ity enhancement attained by modification at the C-2 position of the ꢀ-D-
mannopyranoside residue resulted in the ꢀ-D-mannopyranosyl polymer which
has the same affinity as that of the ꢁ-D-mannopyranosyl polymer.
*Corresponding author.
121
Copyright © 2001 by Marcel Dekker, Inc.
www.dekker.com

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AKAI ET AL.
INTRODUCTION
Concanavalin A (Con A) binds ꢁ-D-mannopyranoside in preference to other
mono-carbohydrate ligands and this specificity has been extensively investi-
gated.1 The 3-, 4-, and 6-hydroxyl groups of D-mannopyranoside are essential for
Con A binding. On the other hand, the Con A binding affinity toward ꢀ-D-
mannopyranoside is only one-fortieth that of ꢁ-D-mannopyranoside1 due to steric
hindrance of the glycosyl bond in the binding site.1 In addition, X-ray crystallo-
graphic analysis showed that the oxygen atom at the anomeric position and the
2-hydroxyl group of ꢁ-D-mannopyranoside is positioned out of the binding site
of Con A.2 This result suggests that the 2-hydroxyl group is not specifically rec-
ognized.
In order to synthesize an effective inhibitor against carbohydrate-processing
enzymes, for use as in in vivo assays, resistance toward exo-glycosidase digestion
is essential. With this goal in mind, several inhibitors such as S- or C-glycosyl ana-
logues have been synthesized by other researchers.3,4 In our work, we planned to
synthesize a new class of inhibitor based on a ꢀ-D-mannopyranoside scaffold,
which can resist exo-ꢁ-D-mannosidase, which is relatively abundant compared
with the low levels of ꢀ-D-mannosidase present in the in vivo assay environment.
However, the binding affinity of ꢀ-D-mannopyranoside is significantly less than
that of the ꢁ-isomer, as mentioned above. In order to enhance the low binding
affinity of a ꢀ-D-mannopyranoside scaffold, several methods were considered.
Recently, two approaches for enhancement of the binding affinity of carbo-
hydrate ligands have been reported. One is the use of a multivalent glycoconjugate
to take advantage of the multivalency effect.5–16 The other approach is to modify
the carbohydrate ligand with an enhancer17 for binding affinity. Specifically, one
of the hydroxyl groups positioned away from the binding site of the receptor, is
modified with an enhancer. We thought that these two approaches could be com-
bined effectively to enhance the binding affinity of carbohydrate ligands to recep-
tors. However, such a combined approach had not been reported. Therefore, we set
out to determine whether a combined multivalency effect and enhancer modifica-
tion would result in ꢀ-D-mannopyranoside possessing sufficient binding affinity
toward Con A. We expected the substitution of the 2-hydroxyl group of ꢀ-D-
mannopyranoside with an enhancer to result in increased binding affinity. In this
work, we examined substitution of the 2-hydroxyl with hydrogen (deoxy),18,19 flu-
oro,18,19 and acetamide groups, because hydrogen atoms are known to enhance
binding affinity through hydrophobic interactions and fluorine acts as a proton
acceptor for hydrogen bonds. The acetamide group is thought to act as both a pro-
ton donor and a proton acceptor in addition to participating in hydrophobic
interactions.
In this paper, we describe the synthesis and the Con A binding ability of
several styryl polymers containing ꢀ-D-mannopyranoside analogues containing
binding enhancers to illustrate this approach for the construction of novel in-
hibitors.

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SYNTHESIS OF NEW GLYCOPOLYMERS
123
RESULTS AND DISCUSSION
Synthesis
For the synthesis of glycopolymers, we selected a styryl derivative as the
monomer. Further, 3-(p-hydroxyphenyl)propionic acid was selected as the spacer,
since an aromatic ring at the anomeric position of D-mannopyranoside increases
the binding affinity over that of the methyl glycoside.1 In addition, the propionic
acid residue was used to distance the polymer backbone from the carbohydrate
residue and thus enable efficient binding with Con A.
We started by synthesizing the glycopolymers 6 containing the spacer-armed
ꢁ-D-mannopyranoside as the standard compound for the Con A binding assay. The
ꢁ-D-mannopyranoside derivative 2 was prepared by glycosylation of 1,2,3,4,6-
penta-O-acetyl-D-mannopyranose with benzyl 3-(p-hydroxyphenyl)propionate in
83% yield, and then reduced in the presence of 10% Pd(OH)2-C/H2 in EtOH to
give the corresponding carboxylic acid derivative 3 in 97% yield. Condensation of
3 with p-vinylbenzylamine16 by the use of 1-ethyl-3-(3-dimethylaminopropyl)car-
bodiimide (WSC) in dichloromethane gave the corresponding amide derivative 4
in 73% yield. Subsequently, O-deacetylation of 4 with NaOMe/MeOH gave p-[2-
(N-p-vinylbenzyl)carbamoyl]ethyl]phenyl ꢁ-D-mannopyranoside 5, in 97% yield,
as a glycomonomer containing the ꢁ-D-mannopyranoside residue on its side chain.
Finally, the ꢁ-D-mannopyranosyl polymer 6 was obtained via radical polymeriza-
tion of 5 by treatment with 2,2ꢂ-azobisisobutyronitrile (AIBN), in 98% yield
(Scheme 1).
For the synthesis of the ꢀ-D-mannopyranoside derivatives, we employed a
method developed previously in our laboratory to form the ꢀ-D-mannopyranosyl
linkage (Scheme 2).20 In this way, we synthesized glycomonomers containing the
Scheme 1.

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AKAI ET AL.
Scheme 2.
spacer-armed ꢀ-D-mannopyranoside derivative 12, the 2-acetamido-2-deoxy-ꢀ-D-
mannopyranoside derivative 15, the 2-deoxy-ꢀ-D-arabino-hexopyranoside deriva-
tive 16, and the 2-deoxy-2-fluoro-ꢀ-D-mannopyranoside derivative 17 starting
from the ꢀ-D-galactopyranoside derivative 10 (Schemes 2 and 3). Compound 10
was synthesized as follows. Glycosylation of 1,2,3,4,6-penta-O-acetyl-ꢀ-D-galac-
topyranose 7 with benzyl 3-(p-hydroxyphenyl)propionate in the presence of
tin(IV) chloride gave the corresponding ꢀ-D-galactopyranoside 8 in 59% yield,
which was then treated with NaOBn/BnOH in dichloromethane to give p-[2-(ben-
Scheme 3.

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SYNTHESIS OF NEW GLYCOPOLYMERS
125
zyloxycarbonyl)ethyl]phenyl ꢀ-D-galactopyranoside 9 in 74% yield. Selective
stannylation of 9 with bis(tributyltin) oxide and subsequent pivaloylation were per-
formed in 66% yield (2 steps). The resulting pivaloate 10 was then treated with tri-
fluoromethanesulfonic anhydride in pyridine at ꢃ19°C to give the 2,4-bistriflate
derivative 11 in quantitative yield. Simultaneous nucleophilic substitution reac-
tions at the C-2 and C-4 positions of 11 with cesium acetate (3.0 mol equiv) af-
forded the ꢀ-D-mannopyranoside derivative 12 in 87% yield. The structure of 12
1
was identified by H NMR (J3,4 ꢄ 9.7 Hz, J4,5 ꢄ 9.7 Hz, J1,2 ꢄ 1.2 Hz and J2,3
ꢄ 3.0 Hz). When a small amount of cesium acetate (1.2 mol equiv) was used, the
reaction afforded the 4-O-acetyl glucopyranoside 13 exclusively (92%) (Scheme
2). This ꢀ-D-glucopyranoside derivative (2-triflate) 13 was treated with n-Bu4NN3,
n-Bu4NBH4,20,21 or n-Bu4NF,20,22 under ultrasonication conditions to afford the
corresponding manno-type 2-azido 14, 2-deoxy 16, and 2-fluoro 17 derivatives, re-
spectively, in moderate yields (Scheme 3). Catalytic reduction of the azido group
of 14 and subsequent acetylation gave the desired 2-acetamido-ꢀ-D-mannopyra-
noside derivative 15 in 53% yield as well as unreacted 14 (42%). ꢀ-D-Mannopyra-
nosyl derivatives 12, 15, 16, and 17 thus obtained were then hydrogenolyzed to
give the corresponding carboxylic acid derivatives 18 (95%), 19 (91%), 20 (92%),
and 21 (90%), respectively. Condensation of 18, 19, 20, and 21 with p-vinylben-
zylamine16 led to the corresponding amide derivatives 22, 23, 24, and 25 in 67, 81,
76, and 61% yields, respectively. O-Deacylation of 22, 23, 24, and 25 with
NaOMe/MeOH, was performed in near quantitative yield to afford the desired
p-[3-(N-p-vinylbenzyl)carbamoyl]ethyl]phenyl glycomonomers of ꢀ-D-mannopy-
ranoside 26, 2-deoxy-2-acetamido-ꢀ-D-mannopyranoside 27, 2-deoxy-ꢀ-D-
arabino-hexopyranoside 28, and 2-deoxy-2-fluoro-ꢀ-D-mannopyranoside 29,
respectively. A polymerization reaction with 2,2ꢂ-azobisisobutyronitrile (AIBN) in
dimethylsulfoxide was performed to give the corresponding glycopolymers 30, 31,
32 and 33 containing ꢀ-D-mannopyranoside (97% yield), 2-acetamido-2-deoxy-ꢀ-
D-mannopyranoside (84% yield), 2-deoxy-2-fluoro-ꢀ-D-mannopyranoside (86%
yield), 2-deoxy-ꢀ-D-arabino-hexopyranoside (56% yield) residues, respectively
(Scheme 4). The averaged molecular weights and reduced viscosities were ana-
lyzed by gel permeation chromatography (GPC). The physical properties of the
synthesized glycopolymers are shown in Table 1.
Con A Binding Assay
Binding assays of the synthetic glycopolymers toward Con A was performed
using the enzyme linked lectin assay (ELLA)23–25 method, which is a standard as-
say in the field. Soybean lectin with high mannose-type sugar chains was coated
on a 96-well test plate and then used for the ELLA. The results are shown in Table
2.
The inhibition abilities of methyl ꢁ-D-mannopyranoside 35 and methyl ꢁ-D-
glucopyranoside 36 show the same relative binding abilities in our assay system as
in the published data.24 The binding affinity of methyl ꢁ-D-glucopyranoside 36

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AKAI ET AL.
Table 1. Physical Properties of Glycopolymers
Polymers
Mna ꢅ 10ꢃ4
Mw / Mna
ꢆred [dL/g]b
6
30
31
32
33
6.3
5.1
2.3
5.3
7.6
1.90
1.45
1.65
1.63
1.53
0.47
0.12
0.10
0.18
0.33
a Determined by GPC based on polystyrene;
b Measured at 30 °C in DMSO.
Table 2. Inhibition Ability of Glycopolymers
Number of
Monomer
Relative
Potency
Polymers
IC50 [M]
Monovalency-IC50 [mM]
6
30
31
1.51 ꢅ 102
1.22 ꢅ 102
50.1
2.0 ꢅ 10ꢃ2
3.1 ꢅ 10ꢃ1
—
3.0
37
—
5.6 ꢅ 102
45
—
2.1
32
1.32 ꢅ 102
1.81 ꢅ 102
1.00
6.0
8.0 ꢅ 102
7.2
33
4.0 ꢅ 10ꢃ2
1.7 ꢅ 103
2.5 ꢅ 103
2.4 ꢅ 102
1.0
35a
36b
1.7 ꢅ 103
2.5 ꢅ 103
1.00
6.9 ꢅ 10ꢃ1
a Methyl ꢁ-D-mannopyranoside: 35; bMethyl ꢁ-D-glucopyranoside: 36.

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127
was measured to be 70% of that of ꢁ-D-mannopyranoside 35. In polymers, the in-
hibition ability of 2-deoxy-ꢀ-D-mannosyl polymer 32 is shown to be only 2.1 times
stronger than that of ꢁ-D-mannopyranoside 35 despite the multivalency. Also, 2-
deoxy-2-acetamido-ꢀ-D-mannosyl polymer 31 showed no inhibitory activity. For
a natural-type mannopyranosyl polymer, ꢁ-D-mannopyranosyl polymer 6 dis-
played potent inhibition activity (3.0 ꢇM/residue). The binding affinity of the ꢀ-
D-mannopyranosyl polymer 30 was one-twelfth of that of the ꢁ-D-mannopyranosyl
polymer 6 due to the multivalency effect. Further, the inhibition potency was dra-
matically improved by the fluoro substituent of 33 resulting in a level comparable
to that of the ꢁ-D-mannopyranosyl polymer 6.
Con A recognizes ꢁ-D-mannopyranoside in strong preference to other mono-
carbohydrate ligands. When ꢀ-D-mannopyranoside is used as a ligand, the binding
affinity is one-fortieth of that of ꢁ-D-mannopyranoside.1 This tendency was also
observed with the carbohydrate polymers 6 and 30. The binding ability of the
ꢀ-D-mannopyranosyl polymer 30 is one-twelfth of that of the corresponding ꢁ-D-
mannopyranosyl polymer 6, but the binding ability of ꢀ-D-mannopyranosyl poly-
mer 30 is 45 times larger than that of methyl ꢁ-D-mannopyranoside 36. These
enhanced binding affinities almost certainly result from the multivalency effect.
The hydrogen (deoxy) and acetamide groups at C-2 did not result in a notable en-
hancement in binding affinity. In contrast, the fluorine atom at C-2 enhanced the
binding affinity of the ꢀ-D-mannopyranosyl polymer to the same level as that of
the ꢁ-D-mannopyranosyl polymer. From this result we speculate that the fluorine
atom at C-2 forms a hydrogen bond with an amino acid at the entrance of the Con
A binding site, resulting in enhanced binding affinity. Recently, H. Tanaka and
co-workers synthesized a glycoconjugate polymer carrying a 3,6-branched ꢁ-D-
mannopyranosyl trisaccharide26 on its scaffold.27 Although it would seem that us-
ing a natural-type branched oligosaccharide residue would be most effective for
increasing the binding ability, it is also important to consider the special properties
of synthetic derivatives as inhibitors for use with in vivo assays, both for binding
affinity and for resistance to exo-glycosidase digestion.
In conclusion, we have succeeded in the synthesis of new styryl polymers
containing ꢀ-D-mannopyranose derivatives and found them to be potent inhibitors
of exo-ꢁ-mannosidase digestion. We believe this to be the first report of such
polymers. The results of Con A binding affinity studies show that some of these
novel glycopolymers display impressive properties. We feel that the new approach
described herein, which combines the multivalency effect and enhancer tech-
niques, constitutes an exciting advance for the synthesis of highly potent inhibitors
resistant to exo-glycosidase digestion.
EXPERIMENTAL
General Methods. All melting points were uncorrected. The solutions
were concentrated under reduced pressure at a bath temperature not exceeding
45°C. The optical rotations were measured in a 0.5 dm tube with JASCO DIP-140

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AKAI ET AL.
polarimeter in chloroform unless otherwise stated. 1H NMR spectra were recorded
with a JEOL EX-90, JEOL FX-200, JEOL EX-270, or JEOL A-500 spectrometer.
IR spectra were recorded with a Hitachi 270-30 spectrometer. Elemental analyses
were performed on a Perkin-Elmer 2400 II elemental analyzer. The chemical
shifts, coupling constants, and IR frequencies were recorded in ꢈ, Hz, and cmꢃ1
units, respectively. Column chromatography was performed on silica gel (Silica
gel 60, 70-230 mesh, Merck). Thin-layer chromatography (TLC) on silica gel (Sil-
ica gel 60 F254, Merck) was used to monitor the reactions and to certify the reac-
tion products. The molecular weights of the glycopolymers were estimated by gel
permeation chromatography (GPC) with the use of a TOSO Model HLC-8020
GPC equipped with a refractive index detector using TSK gel columns (Tosoh Co.
Ltd.) (eluent: N,N-dimethylformamide, calibrated with narrow molecular weight
polystyrene standards).
p-[2-(Benzyloxycarbonyl)ethyl]phenyl
2,3,4,6-Tetra-O-acetyl-ꢁ-D-
mannopyranoside (2). To a solution of 1,2,3,4,6-penta-O-acetyl-ꢁ,ꢀ-D-
mannnopyranose (1) (558 mg, 1.6 mmol), benzyl 3-(p-hydroxyphenyl)propionate
(34) (665 mg, 2.6 mmol), and molecular sieves 4A in dry dichloromethane (20
mL), trimethylsilyl trifluoromethanesulfonate (0.31 mL, 1.6 mmol) was added
dropwise under argon at 0°C. The reaction mixture was stirred at room tempera-
ture for 12 h until the disappearance of 1 on TLC with hexane/ethyl acetate (3/1
v/v). Triethylamine (1 mL) was added to the reaction mixture at 0°C, then molec-
ular sieves were filtered off. The filtrate was poured into a saturated aq NaHCO3
solution, extracted with ethyl acetate, washed with brine and water, dried over an-
hydrous magnesium sulfate, filtered, and concentrated to give a residue. The re-
maining residue was purified on a column of silica gel with hexane/ethyl acetate
(3/1 v/v) to give 2 (692 mg, 83%): [ꢁ]D25 ꢉ58.2° (c 2.1, CHCl3); IR (cmꢃ1) 1743
1
(CꢄO); H NMR (FX-200, CDCl3) ꢈ 7.37–7.29 (m, 5H, -CH2Ph, J ꢄ 8.8 Hz),
7.12, 6.99 (each d, 4H, phenylene), 5.56 (dd, 1H, H-3, J3,4 ꢄ 9.9 Hz), 5.47 (dd, 1H,
H-1, J1,2 ꢄ 1.8 Hz), 5.43 (dd, 1H, H-2, J2,3 ꢄ 3.6 Hz), 5.37 (t, 1H, H-4, J4,5 ꢄ 10.1
Hz), 5.10 (s, 2H, -CH2Ph), 4.27 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 5.1 Hz), 4.10 (ddd, 1H, H-
5, J5,6 ꢄ 2.4 Hz), 4.05 (dd, 1H, H-6, J6,6ꢂ ꢄ 12.2 Hz), 2.93 (t, 2H, -CH2CH2CO-,
J ꢄ 8.0 Hz), 2.65 (t, 2H, -CH2CH2CO-), 2.19, 2.05, 2.03, 2.02 (each s, 3H ꢅ 4,
OAc).
Anal. Calcd for C30H34O12: C, 61.43; H, 5.84. Found: C, 61.41; H, 5.88.
p-(2-Carboxyethyl)phenyl 2,3,4,6-Tetra-O-acetyl-ꢁ-D-mannopyranoside
(3). p-[2-(Benzyloxycarbonyl)ethyl]phenyl glycoside 2 (1.60 g, 2.7 mmol) was
hydrogenolyzed in ethanol (25 mL) in the presence of a catalytic amount of 10%
Pd(OH)2-C/H2 for 2 h until the disappearance of 2 on TLC with hexane/ethyl ac-
etate (3/1 v/v). The solution was then filtered through a pad of celite and concen-
25
trated to afford 3 (1.34 g, 97% yield): [ꢁ]D ꢉ67.4° (c 0.8, CHCl3); IR (cmꢃ1
3192 (OH), 1748 (CꢄO); H NMR (FX-200, CDCl3) ꢈ 7.13, 7.00 (each d, 4H,
phenylene, J ꢄ 8.1 Hz), 6.78 (br s, 1H, COOH), 5.55 (dd, 1H, H-3, J3,4 ꢄ 10.0 Hz),
5.48 (dd, 1H, H-1, J1,2 ꢄ 1.9 Hz), 5.43 (dd, 1H, H-2, J2,3 ꢄ 3,4 Hz), 5.36 (dd, 1H,
)
1

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129
H-4, J4,5 ꢄ 10.0 Hz), 4.28 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 5.1 Hz, J6,6ꢂ ꢄ 12.0 Hz), 4.13–4.04
(m, 2H, H-5 and H-6), 2.89 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.61 (t, 2H, -
CH2CH2CO-), 2.20, 2.05, 2.03, 2.03 (each s, 3H ꢅ 4, OAc).
Anal. Calcd for C23H28O12: C, 55.65; H, 5.68. Found: C, 55.45; H, 5.72.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl 2,3,4,6-Tetra-O-acetyl-
ꢁ-D-mannopyranoside (4). To a solution of p-(2-carboxyethyl)phenyl glyco-
side 3 (1.27 g, 2.50 mmol) and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
(WSC) (585 mg, 3.05 mmol) in dichloromethane (100 mL), a solution of p-vinyl-
benzylamine16 (378 mg, 2.82 mmol) in dichloromethane (40 mL) was added
dropwise at 0°C, and stirred for 1 h until the disappearance of 3 on TLC with
hexane/ethyl acetate (1/1 v/v). The reaction mixture was diluted with di-
chloromethane, washed with 10 % aq citric acid solution, brine and water, dried
over anhydrous magnesium sulfate, filtered, and concentrated to give a residue.
The remaining residue was purified on a column of silica gel with hexane/ethyl ac-
25
etate (3/5 v/v) to afford 4 (1.14 g, 73% yield): [ꢁ]D ꢉ66.0° (c 0.7, CHCl3); IR
(cmꢃ1) 1758 (CꢄO), 1650 (CꢄC); 1H NMR (A-500, CDCl3) ꢈ 7.34, 7.12 (each d,
4H, styryl phenylene, J ꢄ 7.9 Hz), 7.12, 6.99 (each d, 4H, phenylene, J ꢄ 8.5 Hz),
6.69 (dd, 1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.6 Hz, Jcis ꢄ 11.2 Hz), 5.73 (dd, 1H, Ha,
Jgem ꢄ 0.7 Hz), 5.71 (t, 1H, -CONH-), 5.56 (dd, 1H, H-3, J3,4 ꢄ 9.9 Hz), 5.47 (dd,
1H, H-1, J1,2 ꢄ 1.8 Hz), 5.43 (1H, dd, H-2, J2,3 ꢄ 3.6 Hz), 5.37 (1H, dd, H-4, J4,5
ꢄ 10.1 Hz), 5.23 (1H, dd, Hb), 4.37 (2H, d, -NHCH2-, JNH,CH2 ꢄ 5.8 Hz), 4.27
(1H, dd, H-6ꢂ, J5,6ꢂ ꢄ 5.1 Hz), 4.10 (1H, ddd, H-5, J5,6 ꢄ 2.4 Hz), 4.05 (dd, 1H, H-
6, J6,6ꢂ ꢄ 12.2 Hz), 2.94 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.47 (t, 2H,
-CH2CH2CO-), 2.19, 2.05, 2.03, 2.02 (each s, 3H ꢅ 4, OAc).
Anal. Calcd for C32H37O11N: C, 62.84; H, 6.10; N, 2.15. Found: C, 62.42; H,
6.55; N, 2.26.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl ꢁ-D-Mannopyranoside
(5). To a solution of p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl glycoside 4
(1.14 g, 1.86 mmol) in methanol (25 mL), sodium methoxide (1.9M methanol so-
lution) was carefully added at pH 10, stirred for 2 h until the disappearance of 4 on
TLC with hexane/ethyl acetate (1/2 v/v). The reaction mixture was neutralized
with Dowex 50W-X8 (Hꢉ form) ion-exchange resin, filtered, and concentrated to
give pure styryl monomer containing carbohydrate residue 5 (756 mg, 97% yield):
mp 171–174°C (methanol); [ꢁ]D25 ꢉ83.6° (c 0.7, CHCl3); IR (cmꢃ1) 3284 (OH),
1640 (CꢄO, CꢄC); 1H NMR (A-500, d6-DMSO) ꢈ 8.35 (t, 1H, NH), 7.33, 6.98
(each d, 4H, styryl phenylene, J ꢄ 8.2 Hz), 7.12, 7.11 (each d, 4H, phenylene,
J ꢄ 8.6 Hz), 6.68 (dd, 1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.4 Hz, Jcis ꢄ 10.8 Hz),
5.76, 5.73 (dd, 1H, Ha, Jgem ꢄ 0.9 Hz), 5.35 (d, 1H, H-1, J1,2 ꢄ 1.9 Hz), 5.21 (dd,
1H, Hb), 4.26 (d, 2H, -NHCH2-, JNH,CH2 ꢄ 5.5 Hz), 3.89 (d, 1H, H-2, J2,3 ꢄ 3.3
Hz), 3.75 (dd, 1H, H-3, J3,4 ꢄ 9.2 Hz), 3.63–3.57 (m, 3H, H-4, H-6, and H-6ꢂ), 3.49
(ddd, 1H, H-5, J4,5 ꢄ 9.5 Hz, J5,6 ꢄ 2.7 Hz, J5,6ꢂ ꢄ 5.2 Hz), 3.39 (s, 4H, OH), 2.83
(t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.45 (t, 2H, -CH2CH2CO-); 13C NMR (A-500,
d6-DMSO) ꢈ 171.32 (CꢄO), 138.87, 135.54, 134.46, 128.95, 127.20, 125.71 (Ph),

ORDER
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130
AKAI ET AL.
136.12 (CHꢄCH2), 113.33 (CHꢄCH2), 98.95 (C-1), 74.14 (C-2), 70.61 (C-3),
69.96 (C-4), 66.67 (C-5), 60.90 (C-6), 41.69, 37.11, 30.29 (CH2).
Anal. Calcd for C24H29O76N: C, 65.00; H, 6.59; N, 3.16. Found: C, 64.82; H,
6.30; N, 2.70.
Poly[p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl ꢁ-D-mannopyra-
noside] (6). To a solution of 5 (726 mg, 1.64 mmol) in DMSO (2.0 mL), 2,2ꢂ-
azobisisobutyronitrile (4.0 mg, 0.02 mmol) was added. The mixture was set in a
sealed tube, degassed with argon, and kept at 65°C in oil bath for 24 h. The reac-
tion mixture was poured into stirred acetone, and the precipitate was filtered using
a glass filter to give 6 (710 mg, 98% yield): IR (cmꢃ1) 3408 (OH), 1646 (CꢄO);
13C NMR (A-500, d6-DMSO) ꢈ 171.32 (CꢄO), 128.99, 116.65 (Ph), 126.52 (-CH-
CH2-), 99.00 (C-1), 74.58 (C-2), 70.66 (C-3), 70.09 (C-4), 66.69 (C-5), 60.99
(C-6), 41.72, 40.41, 37.19, 30.33 (CH2).
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 2,3,4,6-Tetra-O-acetyl-ꢀ-D-galac-
topyranoside (8). To a mixture of 7 (15.0 g, 384 mmol) and 34 (10.8 g, 422 mmol)
in dry CH2Cl2 (300 mL), anhydrous tin(IV) chloride (5.0 mL, 422 mmol) was added
dropwise under argon at ꢃ19°C. The reaction mixture was kept with stirring for 1
h until the disappearance of 7 on TLC with hexane/ethyl acetate (3/1 v/v). The re-
action mixture was poured into a saturated aq NaHCO3 solution with activated
potassium fluoride (5.0 g), and stirred for 12 h. The above mixture was filtered and
extracted with CHCl3. The combined organic solution was washed with brine and
water, dried over anhydrous magnesium sulfate, filtered, and concentrated to give
a residue. The remaining residue was purified on a column of silica gel with hex-
ane/ethyl acetate (3/1 v/v) to afford 8 (13.8 g, 59% yield): mp 108–109°C (ethanol-
hexane); [ꢁ]D25 ꢃ13.4° (c 0.9, CHCl3); IR (cmꢃ1) 1752 (CꢄO); 1H NMR (FX-200,
CDCl3) ꢈ 7.37–7.26 (m, 4H, -CH2Ph), 7.11, 6.99 (each d, 4H, phenylene, J ꢄ 8.8
Hz), 5.48 (dd, 1H, H-2, J2,3 ꢄ 10.5 Hz), 5.45 (dd, 1H, H-4, J4,5 ꢄ 0.9 Hz), 5.10 (dd,
1H, H-3, J3,4 ꢄ 3.4 Hz), 5.10 (s, 2H, -CH2Ph), 5.00 (d, 1H, H-1, J1,2 ꢄ 7.8 Hz),
4.25–4.04 (m, 3H, H-5, H-6, and H-6ꢂ), 2.93 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.65
(t, 2H, -CH2CH2CO-), 2.18, 2.07, 2.06, 2.01 (each s, 3H ꢅ 4, OAc).
Anal. Calcd for C30H34O12: C, 61.43; H, 5.84. Found: C, 61.41; H, 5.88.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl ꢀ-D-Galactopyranoside (9). To
a solution of 8 (200 mg, 0.34 mmol) in CH2Cl2 (50 mL), 1M NaOBn in BnOH was
carefully added at pH 11 at 0°C, and stirred for 1 h until the disappearance of 9 on
TLC with hexane/ethyl acetate (3/1 v/v). The reaction mixture was neutralized
with Dowex 50W-X8 (Hꢉ form) ion-exchange resin, filtered, and concentrated to
give a residue. The remaining residue was purified on a column of silica gel with
25
CHCl3/MeOH (8/1 v/v) to afford 9 (120 mg, 74% yield): [ꢁ]D ꢃ25.4° (c 0.9,
MeOH); mp 86–87.5°C (methanol-ether); IR (cmꢃ1) 3369 (OH), 1730 (CꢄO); 1H
NMR (A-500, CD3OD) ꢈ 7.24–7.14 (m, 5H, -CH2Ph), 7.11, 7.02 (each d, 4H,
phenylene, J ꢄ 8.8 Hz), 5.10 (s, 2H, -CH2Ph), 4.84 (d, 1H, H-1, J1,2 ꢄ 7.6 Hz),

ORDER
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SYNTHESIS OF NEW GLYCOPOLYMERS
131
3.93 (dd, 1H, H-4, J4,5 ꢄ 1.0 Hz), 3.82 (dd, 1H, H-2, J2,3 ꢄ 9.8 Hz), 3.81 (dd, 1H,
H-6ꢂ. J6,6ꢂ ꢄ 11.3 Hz), 3.77 (dd, 1H, J5,6 ꢄ 6.7 Hz), 3.69 (ddd, 1H, H-5, J5,6ꢂ ꢄ 5.2
Hz), 3.60 (dd, 1H, H-3, J3,4 ꢄ 3.7 Hz), 2.90 (t, 2H, -CH2CH2CO-, J ꢄ 7.6 Hz), 2.66
(t, 2H, -CH2CH2CO-).
Anal. Calcd for C22H26O8: C, 63.15; H, 6.26. Found: C, 63.35; H, 6.26.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 3,6-Di-O-pivaloyl-ꢀ-D-galactopy-
ranoside (10). A solution of 9 (300 mg, 0.72 mmol) and bis(tributyltin) oxide
(1.31 g, 2.2 mmol) in toluene was refluxed for 2 h with a Dean-Stark apparatus,
then pivaloyl chloride (2.5 mL, 2.09 mmol) was added at 0°C and stirred for 72 h
at rt until the disappearance of 9 on TLC with chloroform/methanol (8/1 v/v). The
mixture was diluted with ethyl acetate (50 mL), treated with a saturated aq
NaHCO3 solution and activated potassium fluoride, filtered, and separated. The
aqueous solution was extracted with ethyl acetate. The combined organic solution
was washed with brine and water, dried over anhydrous magnesium sulfate, fil-
tered, and concentrated to give a residue. The remaining residue was purified on a
column of silica gel with hexane/ethyl acetate (2/1 v/v) to afford 10 (278 mg, 66%
yield): mp 104–105°C (ethanol-hexane); [ꢁ]D25 ꢉ17.4° (c 0.5, CHCl3); IR (cmꢃ1
)
3548 (OH), 1724 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 7.37–7.28 (m, 5H, -CH2Ph),
7.08, 6.97 (each d, 4H, phenylene, J ꢄ 8.5 Hz), 5.10 (s, 2H, -CH2Ph), 4.93 (dd, 1H,
H-3, J3,4 ꢄ 10.1 Hz), 4.88 (d, 1H, H-1, J1,2 ꢄ 7.7 Hz), 4.36 (dd, 1H, H-6, J6,6ꢂ
ꢄ 11.6 Hz), 4.29 (dd, 1H, H-6ꢂ), 4.12 (ddd, 1H, H-2, J2,3 ꢄ 3.4 Hz), 4.04 (dd, 1H,
H-4), 3.89 (dd, 1H, H-5, J5,6 ꢄ 5.2 Hz, J5,6ꢂ ꢄ 7.4 Hz), 2.91 (t, 2H, -CH2CH2CO,
J ꢄ 7.7 Hz), 2.64 (t, 2H, -CH2CH2CO-), 2.46 (d, 1H, OH, J2,OH ꢄ 3.3 Hz), 2.21
(d, 1H, OH, J4,OH ꢄ 4.9 Hz), 1.27, 1.20 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C32H42O10: C, 65.26; H, 7.22. Found: C, 65.26; H, 7.22.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 3,6-Di-O-pivaloyl-2,4-bis(O-tri-
fluoromethylsulfonyl)-ꢀ-D-galactopyranoside (11). To a solution of 10 (100
mg, 0.17 mmol) in pyridine (10 mL), trifluoromethanesulfonic anhydride (0.1 mL,
0.59 mmol) was added under argon at ꢃ19°C. The reaction mixture was stirred at
room temperature for 4 h until the disappearance of 10 on TLC with hexane/ethyl
acetate (2/1 v/v). The reaction mixture was poured into a saturated aq NaHCO3 so-
lution and extracted with CHCl3. The combined organic layer was washed with
brine and water, dried over anhydrous magnesium sulfate, and concentrated to give
a residue. The remaining residue was purified on a short column of silica gel with
hexane/ethyl acetate (3/1 v/v) to afford 10 (145 mg, quantitatively): IR (cmꢃ1
)
1
2974 (OH), 1740 (CꢄO); H NMR (FX-200, CDCl3) ꢈ 7.40–7.28 (m, 5H, -CH2
Ph), 7.12, 6.94 (each d, 4H, phenylene, J ꢄ 8.8 Hz), 5.36 (d, 1H, H-4, J3,4
ꢄ 2.7 Hz), 5.23 (dd, 1H, H-2, J2,3 ꢄ 9.3 Hz), 5.22 (dd, 1H, H-3), 5.20 (d, 1H, H-
1, J1,2 ꢄ 6.8 Hz), 5.11 (s, 2H, -CH2Ph), 4.37 (dd, 1H, H-6, J6,6ꢂ ꢄ 10.5 Hz), 4.19
(dd, 1H, H-5, J5,6ꢂ ꢄ 6.1 Hz), 4.08 (dd, 1H, H-6, J5,6 ꢄ 6.1 Hz), 2.94 (t, 2H,
-CH2CH2CO-, J ꢄ 7.8 Hz), 2.65 (t, 2H, -CH2CH2CO-), 1.31, 1.21 (each s, 9H ꢅ
2, OPiv).

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AKAI ET AL.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 2,4-Di-O-acetyl-3,6-di-O-pival-
oyl-ꢀ-D-mannopyranoside (12). The reaction mixture of 11 (145 mg, 0.17
mmol), cesium acetate (98 mg, 0.51 mmol, 3.0 mol equiv) and 18-crown-6 ether
(135 mg, 0.51 mmol) in dry benzene (30 mL) was stirred overnight under ultra-
sonication for 12 h until the disappearance of 11 on TLC with hexane/ethyl acetate
(3/1 v/v). The reaction mixture was diluted with ethyl acetate, washed with brine
and water, dried over anhydrous magnesium sulfate, filtered, and concentrated to
give a residue. The remaining residue was purified on a column of silica gel with
hexane/ethyl acetate (3/1 v/v) to afford 12 (99 mg, 87% yield): [ꢁ]D25 ꢃ36.1° (c
0.7, CHCl3); IR (cmꢃ1) 1740 (CꢄO); 1H NMR (FX-200, CDCl3) ꢈ 7.33–7.26 (m,
5H, -CH2Ph), 7.08, 6.92 (each d, 4H, phenylene, J ꢄ 8.7 Hz), 5.69 (dd, 1H, H-2,
J2,3 ꢄ 3.0 Hz), 5.34 (t, 1H, H-4, J4,5 ꢄ 9.7 Hz), 5.17 (d, 1H, H-1, J1,2 ꢄ 1.2 Hz),
5.10 (s, 2H, -CH2Ph), 5.10 (dd, 1H, H-3, J3,4 ꢄ 9.7 Hz), 4.30 (dd, 1H, H-6ꢂ, J6,6ꢂ
ꢄ 12.2 Hz), 4.17 (dd, 1H, H6, J5,6 ꢄ 6.7 Hz), 3.86 (ddd, 1H, H-5, J5,6ꢂ ꢄ 2.4 Hz),
2.91 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.62 (t, 2H, -CH2CH2CO-), 2.20, 2.05
(each s, 3H ꢅ 2, OAc), 1.22, 1.15 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C36H46O12: C, 50.98; H, 5.76. Found: C, 64.03; H, 7.25.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 4-O-Acetyl-3,6-di-O-pivaloyl-2-
O-trifluoromethylsulfonyl-ꢀ-D-glucopyranoside (13). To a solution of 11
(1.27 g, 1.5 mmol) in dry toluene (55 mL), cesium acetate (344 mg, 1.79 mmol)
and 18-crown-6 ether (474 mg, 1.79 mmol, 2.0 mol equiv) were added and stirred
for 4 h at rt until the disappearance of 11 on TLC with hexane/ethyl acetate (3/1
v/v). The reaction mixture was diluted with ethyl acetate, washed with brine and
water, dried over anhydrous magnesium sulfate, filtered, and concentrated to give
a residue. The remaining residue was purified on a column of silica gel with hex-
ane/ethyl acetate (3/1 v/v) to afford 17 (1.04 g, 92% yield): [ꢁ]D25 ꢃ14.6° (c 0.9,
CHCl3); IR (cmꢃ1) 1743 (CꢄO); 1H NMR (FX-200, CDCl3) ꢈ 7.37–7.29 (m, 5H,
-CH2Ph), 7.10, 6.70 (each d, 4H, phenylene, J ꢄ 8.5 Hz), 5.50 (dd, 1H, H-3, J3,4
ꢄ 9.4 Hz), 5.14 (d, 1H, H-1, J1,2 ꢄ 7.9 Hz), 5.13 (dd, 1H, H-4, J4,5 ꢄ 9.4 Hz), 5.10
(s, 2H, -CH2Ph), 4.97 (dd, 1H, H-2, J2,3 ꢄ 9.5 Hz), 4.23 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 2.1
Hz), 4.12 (dd, 1H, H-6, J6,6ꢂ ꢄ 12.2 Hz), 3.89 (ddd, 1H, H-5, J5,6 ꢄ 6.4 Hz), 2.93
(t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.65 (t, 2H, -CH2CH2CO-), 2.04 (s, 3H, OAc),
1.22, 1.21 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C35H43F3O12S: C, 56.44; H, 5.82. Found: C, 56.35; H, 6.15.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 4-O-Acetyl-2-azido-2-deoxy-3,6-
di-O-pivaloyl-ꢀ-D-mannopyranoside (14). To a solution of 13 (839 mg, 1.10
mmol) in dry benzene (30 mL), tetrabutylammonium azide (627 mg, 2.20 mmol)
was added and stirred for 12 h in a water bath under ultrasonication until the dis-
appearance of 13 on TLC with hexane/ethyl acetate (3/1 v/v). The reaction mixture
was diluted with ethyl acetate, washed with brine and water, dried over anhydrous
magnesium sulfate, and concentrated to give a residue. The remaining residue was
purified on a column of silica gel with hexane/ethyl acetate (3/1 v/v) to afford 14
(691 mg, 96% yield): mp 61.5–64°C (ether-hexane); [ꢁ]D25 ꢉ45.0° (c 0.9, CHCl3);

ORDER
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SYNTHESIS OF NEW GLYCOPOLYMERS
133
IR (cmꢃ1) 2112 (N3), 1732 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 7.38–7.29 (m, 5H,
-CH2Ph), 7.02, 6.94 (each d, 4H, phenylene, J ꢄ 8.5 Hz), 5.31 (dd, 1H, H-4, J4,5
ꢄ 9.7 Hz), 5.20 (d, 1H, H-1, J1,2 ꢄ 1.2 Hz), 5.10 (s, 2H, -CH2Ph), 5.02 (dd, 1H,
H-3, J3,4 ꢄ 9.7 Hz), 4.27 (dd, 1H, H-2, J2,3 ꢄ 3.6 Hz), 4.26 (dd, 1H, H-6, J6,6ꢂ
ꢄ
11.9 Hz), 4.13 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 6.7 Hz), 3.77 (1H, ddd, H-5, J5,6 ꢄ 2.4 Hz),
2.92 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.64 (t, 2H, -CH2CH2CO-), 2.04 (s, 3H,
OAc), 1.23, 1.21 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C34H43N3O10: C, 62.47; H, 6.63; N, 6.43. Found: C, 62.75;
H, 6.88; N, 6.34.
p-(Benzyloxycarbonylethyl)phenyl 2-Acetamido-4-O-acetyl-2-deoxy-
3,6-di-O-pivaloyl-ꢀ-D-mannopyranoside (15). Compound 14 (733 mg, 1.12
mmol) was hydrogenolyzed in the presence of a catalytic amount of 5% Pd-C/H2
in benzene (25 mL) for 1 h. The reaction mixture was then filtered through a pad
of celite. The filtrate was treated with acetic anhydride (0.5 mL) at rt for 30 min,
and concentrated to give a residue. The remaining residue was purified on a col-
umn of silica gel with hexane/ethyl acetate (2/1 v/v) to afford 15 (400 mg, 53%
yield) and recovered 14 (311 mg, 42% yield): mp 116–117°C (dec.) (ethanol-hex-
25
1
ane); [ꢁ]D ꢃ5.6° (c 0.7, CHCl3); IR (cmꢃ1) 1737 and 1680 (CꢄO); H NMR
(EX-270, CDCl3) ꢈ 7.37–7.30 (m, 5H, -CH2Ph), 7.08, 6.91 (each d, 4H, phenylene,
J ꢄ 8.5 Hz), 5.82 (d, 1H, NHAc, JNH,2 ꢄ 9.5 Hz), 5.26 (d, 1H, H-1, J1,2 ꢄ 2.1 Hz),
5.15 (t, 1H, H-4, J4,5 ꢄ 8.5 Hz), 5.10 (s, 2H, -CH2Ph), 5.07 (dd, 1H, H-3, J3,4
ꢄ 8.5 Hz), 4.94 (ddd, 1H, H-2, J2,3 ꢄ 3.9 Hz), 4.25 (dd, 1H, H-6, J6,6ꢂ ꢄ 12.2 Hz),
4.02 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 6.7 Hz), 3.89 (ddd, 1H, H-5, J5,6 ꢄ 3.7 Hz), 2.91 (t, 2H,
-CH2CH2CO-, J ꢄ 7.3 Hz), 2.63 (t, 2H, -CH2CH2CO-), 2.07, 2.06 (each s, 6H,
OAc), 1.19, 1.19 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C36H47NO11: C, 64.56; H, 7.07; N, 2.09. Found: C, 64.72; H,
7.14; N, 1.97.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 4-O-Acetyl-2-deoxy-3,6-di-O-pi-
valoyl-ꢀ-D-arabino-hexopyranoside (16). To a solution of 13 (1.01 g, 1.64
mmol) in dry benzene (30 mL), tetrabutylammonium tetrahydroborate (680 mg,
2.70 mmol) was added, and kept for 29 h in a water bath under ultrasonication un-
til the disappearance of 13 on TLC with hexane/1ethyl acetate (3/1 v/v). The reac-
tion mixture was poured into a saturated aq NaHCO3 solution, extracted with ethyl
acetate, washed with brine and water, dried over anhydrous magnesium sulfate,
and concentrated to give a residue. The remaining residue was purified on a col-
umn of silica gel with hexane/ethyl acetate (3/1 v/v) to afford 16 (784 mg, 52%
25
yield): mp 70–71°C (ethanol-hexane); [ꢁ]D ꢃ30.1° (c 1.0, CHCl3); IR (cmꢃ1
)
1737 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 7.37–7.29 (m, 5H, -CH2Ph), 7.09, 6.93
(each d, 4H, phenylene, J ꢄ 8.5 Hz), 5.16 (dd, 1H, H-1, J1,2eq ꢄ 2.0 Hz, J1,2ax
ꢄ 9.4 Hz), 5.10 (s, 2H, -CH2Ph), 5.06 (ddd, 1H, H-3, J3,4 ꢄ 9.5 Hz, J2eq,3 ꢄ 4.6
Hz), 5.04 (dd, 1H, H-4, J4,5 ꢄ 9.5 Hz), 4.24 (dd, 1H, H-6, J5,6 ꢄ 2.4 Hz, J6,6ꢂ
ꢄ 12.1 Hz), 4.13 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 6.9 Hz), 3.78 (ddd, 1H, H-5), 2.91 (t, 2H,
-CH2CH2CO-, J ꢄ 7.8 Hz), 2.64 (t, 2H, -CH2CH2CO-), 2.50 (ddd, 1H, H-2eq,

ORDER
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AKAI ET AL.
J
2eq,2ax ꢄ 12.2 Hz), 2.05 (3H, s, OAc), 1.98 (1H, ddd, H-2ax), 1.21, 1.18 (each s,
9H ꢅ 2, OPiv).
Anal. Calcd for C34H44O10: C, 66.65; H, 7.24. Found: C, 66.55; H, 7.24.
p-[2-(Benzyloxycarbonyl)ethyl]phenyl 4-O-Acetyl-2-deoxy-2-fluoro-3,6-
di-O-pivaloyl-ꢀ-D-mannopyranoside (17). To a solution of 13 (844 mg, 1.11
mmol) in dry benzene (50 mL), tetrabutylammonium fluoride (1M solution in
tetrahydrofuran, 5.6 mL, 0.55 mmol) was added dropwise at 0°C, and the reaction
mixture was stirred for 24 h at rt under argon until the disappearance of 13 on TLC
with hexane/ethyl acetate (3/1 v/v). The reaction mixture was poured into a satu-
rated aq NaHCO3 solution, extracted with ethyl acetate, washed with brine and wa-
ter, dried over anhydrous magnesium sulfate, filtered, and concentrated to give a
residue. The remaining residue was purified on a column of silica gel with hex-
ane/ethyl acetate (3/1 v/v) to afford 17 (258 mg, 37% yield): [ꢁ]D25 ꢃ39.0° (c 0.8,
CHCl3); IR (cmꢃ1) 1737 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 7.37–7.29 (m, 5H,
-CH2Ph), 7.08, 6.91 (each d, 4H, styryl phenylene, J ꢄ 8.6 Hz), 5.41 (dd, 1H, H-4,
J
3,4 ꢄ J4,5 ꢄ 9.8 Hz), 5.12 (dd, 1H, H-1, J1,2 ꢄ 0.3 Hz, J1,F ꢄ 15.2 Hz), 5.10 (s, 2H,
-CH2Ph), 5.02 (ddd, 1H, H-3, J2,3 ꢄ 2.4 Hz, J3,F ꢄ 23.8 Hz), 5.00 (ddd, 1H, H-2,
2,F ꢄ 51.8 Hz), 4.30 (dd, 1H, H-6, J5,6 ꢄ 2.5 Hz, J6,6ꢂ ꢄ 12.2 Hz), 4.16 (dd, 1H, H-
J
6, J5,6ꢂ ꢄ 6.7 Hz), 3.83 (ddd, 1H, H-5), 2.92 (t, 2H, -CH2CH2CO-, J ꢄ 7.9 Hz), 2.64
(t, 2H, -CH2CH2CO-), 2.07 (s, 3H, OAc), 1.22, 1.21 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C34H43FO10; C, 64.75; H, 6.87. Found: C, 65.22; H, 7.01.
p-(2-Carboxyethyl)phenyl
2,4-Di-O-acetyl-3,6-di-O-pivaloyl-ꢀ-D-
mannopyranoside (18). p-[2-(Benzyloxycarbonyl)ethyl]phenyl glycoside 12
(754 mg, 1.12 mmol) was hydrogenolyzed in ethanol (25 mL) in the presence of a
catalytic amount of 10% Pd(OH)2-C/H2 for 2 h until the disappearance of 12 on
TLC with hexane/ethyl acetate (3/1 v/v). The reaction mixture was filtered through
a pad of celite and concentrated to afford 18 (617 mg, 95% yield): [ꢁ]D25 ꢃ44.4°
(c 0.8, CHCl3); IR (cmꢃ1) 3240 (OH), 1746 (CꢄO); 1H NMR (FX-200, CDCl3) ꢈ
7.07, 6.92 (each d, 4H, phenylene, J ꢄ 7.6 Hz), 5.67 (dd, 1H, H-2, J2,3 ꢄ 3.2 Hz),
5.34 (t, 1H, H-4, J4,5 ꢄ 9.8 Hz), 5.19 (s, 1H, H-1), 5.10 (dd, 1H, H-3, J3,4 ꢄ 9.8
Hz), 4.30 (dd, 1H, H-6ꢂ, J6,6ꢂ ꢄ 12.0 Hz), 4.19 (dd, 1H, H-6), 3.84 (ddd, 1H, H-5,
J5,6 ꢄ 6.6 Hz), 2.85 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.58 (t, 2H, -CH2CH2
CO-), 2.20, 2.05 (each s, 6H, OAc), 1.22, 1.15 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C28H40O12: C, 59.14; H, 7.09. Found: C, 59.64; H, 7.08.
p-(2-Carboxyethyl)phenyl 2-Acetamido-4-O-acetyl-2-deoxy-3,6-di-O-pi-
valoyl-ꢀ-D-mannopyranoside (19). p-[2-(Benzyloxycarbonyl)ethyl]phenyl
glycoside 15 (80 mg, 0.12 mmol) was hydrogenolyzed in ethanol (10 mL) in the
presence of a catalytic amount of 10% Pd(OH)2-C/H2 for 1 h until the disappear-
ance of 15 on TLC with hexane/ethyl acetate (2/1 v/v). The reaction mixture was
then filtered through a pad of celite and concentrated to afford 19 (63 mg, 91%
yield): mp 88–91°C (ethanol-hexane); [ꢁ]D ꢃ55.6° (c 0.6, CHCl3); IR (cmꢃ1
25
)
3388 (OH), 1728 and 1644 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 7.10, 6.93 (each d,

ORDER
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SYNTHESIS OF NEW GLYCOPOLYMERS
135
4H, phenylene, J ꢄ 8.5 Hz), 6.80 (br s, 1H, COOH), 5.89 (d, 1H, NHAc, JNH,2
ꢄ 9.1 Hz), 5.27 (d, 1H, H-1, J1,2 ꢄ 1.9 Hz), 5.15 (t, 1H, H-4, J4,5 ꢄ 8.6 Hz), 5.08
(dd, 1H, H-3, J3,4 ꢄ 8.6 Hz), 4.95 (ddd, 1H, H-2, J2,3 ꢄ 4.0 Hz), 4.24 (dd, 1H, H-
6, J6,6ꢂ ꢄ 12.2 Hz), 4.20 (dd, 1H, H-6ꢂ, J6ꢂ,5 ꢄ 6.4 Hz), 3.90 (ddd, 1H, H-5, J5,6
ꢄ 3.6 Hz), 2.89 (t, 2H, -CH2CH2CO-, J ꢄ 7.7 Hz), 2.62 (t, 2H, -CH2CH2CO-),
2.07, 2.06 (each s, 3H ꢅ 2, OAc), 1.19, 1.19 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C29H41NO11: C, 60.09; H, 7.13; N, 2.42. Found: C, 59.80; H,
6.64; N, 2.47.
p-(2-Carboxyethyl)phenyl 4-O-Acetyl-2-deoxy-3,6-di-O-pivaloyl-ꢀ-D-
arabino-hexopyranoside (20). p-[2-(Benzyloxycarbonyl)ethyl]phenyl glyco-
side 16 (610 mg, 1.00 mmol) was hydrogenolyzed in ethanol (50 mL) in the
presence of a catalytic amount of 10% Pd(OH)2-C/H2 for 1 h until the disappear-
ance of 16 on TLC with hexane/ethyl acetate (3/1 v/v). The reaction mixture was
then filtered through a pad of celite and concentrated to afford 20 (476 mg, 92%
yield): mp 147–148°C (ethanol-hexane); [ꢁ]D25 ꢃ35.0° (c 1.0, CHCl3); IR (cmꢃ1
)
3460 (OH), 1734 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 8.58 (br s, 1H, COOH), 7.09,
6.95 (each d, 4H, -CH2Ph, J ꢄ 8.9 Hz), 5.17 (dd, 1H, H-1, J1,2eq ꢄ 2.2 Hz, J1,2ax
ꢄ 9.3 Hz), 5.06 (ddd, 1H, H-3, J3,4 ꢄ 9.4 Hz, J2eq,3 ꢄ 4.6 Hz, J2ax,3 ꢄ 11.2 Hz),
5.04 (dd, 1H, H-4, J4,5 ꢄ 9.5 Hz), 4.24 (dd, 1H, H-6, J5,6 ꢄ 2.4 Hz, J6,6ꢂ ꢄ 12.1
Hz), 4.13 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 6.9 Hz), 3.79 (ddd, 1H, H-5), 2.89 (t, 2H,
-CH2CH2CO-, J ꢄ 7.8 Hz), 2.62 (t, 2H, -CH2CH2CO-), 2.50 (ddd, 1H, H-2eq,
J
2eq,2ax ꢄ 12.2 Hz), 2.05 (s, 3H, OAc), 1.98 (ddd, 1H, H-2ax), 1.21, 1.18 (each s,
9H ꢅ 2, OPiv).
Anal. Calcd for C27H38O10: C, 62.05; H, 7.33. Found: C, 62.26; H, 7.33.
p-(2-Carboxyethyl)phenyl 4-O-Acetyl-2-deoxy-2-fluoro-3,6-di-O-pival-
oyl-ꢀ-D-mannopyranoside (21). p-[2-(Benzyloxycarbonyl)ethyl]phenyl glyco-
side 17 (224 mg, 0.36 mmol) was hydrogenolyzed in ethanol (50 mL) in the
presence of a catalytic amount of 10% Pd(OH)2-C/H2 for 1 h until the disappear-
ance of 17 on TLC with hexane/ethyl acetate (2/1 v/v). The reaction mixture was
then filtered through a pad of celite and concentrated to afford 21 (173 mg, 90%):
mp 168–169°C (ethanol-hexane); [ꢁ]D25 ꢃ40.3° (c 1.0, CHCl3); IR (cmꢃ1) 3358
(OH), 1740 (CꢄO); 1H NMR (A-500, CDCl3) ꢈ 9.25 (br s, 1H, COOH), 7.12, 6.99
(each d, 4H, phenylene, J ꢄ 8.5 Hz), 5.41 (dd, 1H, H-4, J3,4 ꢄ J4,5 ꢄ 9.8 Hz), 5.15
(dd, 1H, H-1, J1,2 ꢄ 0.3 Hz, J1,F ꢄ 17.1 Hz), 5.03 (ddd, 1H, H-3, J2,3 ꢄ 2.5 Hz, J3,F
ꢄ 26.8 Hz), 5.01 (ddd, 1H, H-2, J2,F ꢄ 51.9 Hz), 4.30 (dd, 1H, H-6, J5,6 ꢄ 2.4 Hz,
J6,6ꢂ ꢄ 12.2 Hz), 4.17 (dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 6.7 Hz), 3.85 (ddd, 1H, H-5), 2.90 (t,
2H, -CH2CH2CO-, J ꢄ 7.7 Hz), 2.63 (t, 2H, -CH2CH2CO-), 2.06 (s, 3H, OAc),
1.22 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C27H37FO10: C, 60.00; H, 6.90. Found: C, 60.07; H, 7.13.
p-[2-(N-p-Vinylbenzyl)carbamoyl]ethyl]phenyl 2,4-Di-O-acetyl-3,6-di-
O-pivaloyl-ꢀ-D-mannopyranoside (22). To a solution of p-(2-carboxyethyl)
phenyl glycoside 18 (617 mg, 1.06 mmol) and 1-ethyl-3-(3-dimethylamino-

ORDER
REPRINTS
136
AKAI ET AL.
propyl)carbodiimide (WSC) (275 mg, 1.43 mmol) in dichloromethane (50 mL), a
solution of p-vinylbenzylamine16 (200 mg, 1.52 mmol) in dichloromethane (20
mL) was added dropwise at 0°C, and the reaction mixture was stirred for 1 h until
the disappearance of 18 on TLC with hexane/ethyl acetate (3/1 v/v). The reaction
mixture was diluted with dichloromethane, washed with 10% aq citric acid solu-
tion, brine and water, dried over anhydrous magnesium sulfate, filtered, and
concentrated to give a residue. The remaining residue was purified on a column of
silica gel with hexane/ethyl acetate (3/5 v/v) to afford 22 (496 mg, 67% yield): mp
25
125–129°C (ethanol-hexane); [ꢁ]D ꢃ33.0° (c 0.8, CHCl3); IR (cmꢃ1) 1736
(CꢄO), 1648 (CꢄC); 1H NMR (FX-200, CDCl3) ꢈ 7.34, 7.07 (each d, 4H, styryl
phenylene, J ꢄ 8.3 Hz), 7.11, 6.92 (each d, 4H, phenylene, J ꢄ 8.5 Hz), 6.69 (dd,
1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.6 Hz, Jcis ꢄ 11.0 Hz), 5.74 (dd, 1H, Ha, Jgem
ꢄ 0.9 Hz), 5.68 (dd, 1H, H-2, J2,3 ꢄ 3.2 Hz), 5.60 (t, 1H, -CONH-), 5.34 (t, 1H,
H-4, J4,5 ꢄ 9.8 Hz), 5.25 (dd, 1H, Hb), 5.17 (d, 1H, H-1, J1,2 ꢄ 1.0 Hz), 5.10 (dd,
1H, H-3, J3,4 ꢄ 9.8 Hz), 4.36 (d, 2H, -NHCH2-, JNH,CH2 ꢄ 5.6 Hz), 4.30 (dd, 1H,
H-6ꢂ, J5,6ꢂ ꢄ 7.1 Hz, J6,6ꢂ ꢄ 12.0 Hz), 4.16 (dd, 1H, H-6), 3.84 (ddd, 1H, H-5, J5,6
ꢄ 2.4 Hz), 2.93 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.46 (t, 2H, -CH2CH2CO-),
2.20, 2.05 (each s, 3H ꢅ 2, OAc), 1.21, 1.15 (each s, 9H ꢅ 2, OPiv).
Anal. Calcd for C38H49O11N: C, 59.14; H, 7.09, N, 2.39. Found: C, 65.82; H,
7.26, N, 2.01.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl 2-Acetamido-4-O-
acetyl-2-deoxy-3,6-di-O-pivaloyl-ꢀ-D-mannopyranoside (23). To a solution
of p-(2-carboxyethyl)phenyl glycoside 19 (170 mg, 0.29 mmol) and 1-ethyl-3-(3-
dimethylaminopropyl)carbodiimide (WSC) (67 mg, 0.35 mmol) in dichlo-
romethane (25 mL), a solution of p-vinylbenzylamine16 (5 mg, 0.38 mmol) in
dichloromethane (10 mL) was added dropwise at 0°C, and the reaction mixture was
stirred for 1 h until the disappearance of 19 on TLC with hexane/ethyl acetate (1/3
v/v). The reaction mixture was diluted with dichloromethane, washed with 10% aq
citric acid solution, brine and water, dried over anhydrous magnesium sulfate, fil-
tered, and concentrated to give a residue. The remaining residue was purified on a
column of silica gel with hexane/ethyl acetate/pyridine (25/75/3 v/v/v) to afford 23
25
(124 mg, 81% yield): mp 88–91°C (hexane-ethanol): [ꢁ]D ꢃ44.3° (c 0.9,
CHCl3); IR (cmꢃ1) 1737 (CꢄO), 1653 (CꢄC); 1H NMR (A-500, CDCl3) ꢈ 7.34,
7.11 (each d, 4H, styryl phenylene, J ꢄ 8.3 Hz), 7.09, 6.90 (each d, 4H, phenylene,
J ꢄ 8.5 Hz), 6.70 (dd, 1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.4 Hz, Jcis ꢄ 10.9 Hz), 5.84
(d, 1H, NHAc, JNH,2 ꢄ 9.2 Hz), 5.73 (dd, 1H, Ha, Jgem ꢄ 0.9 Hz), 5.65 (t, 1H, -
CONH-), 5.25 (dd, 1H, Hb), 5.24 (d, 1H, H-1, J1,2 ꢄ 1.8 Hz), 5.15 (t, 1H, H-4, J4,5
ꢄ 8.8 Hz), 5.07 (dd, 1H, H-3, J3,4 ꢄ 8.9 Hz), 4.94 (ddd, 1H, H-2, J2,3 ꢄ 3.9 Hz),
4.38 (1H, d, -NHCH2-, JNH,CH2 ꢄ 5.6 Hz), 4.25 (dd, 1H, H-6, J6,6ꢂ ꢄ 11.9 Hz), 4.19
(dd, 1H, H-6ꢂ, J5,6ꢂ ꢄ 6.7 Hz), 3.88 (ddd, 1H, H-5, J5,6 ꢄ 3.4 Hz), 2.94 (t, 2H,
-CH2CH2CO-, J ꢄ 7.9 Hz), 2.64 (t, 2H, -CH2CH2CO-), 2.07, 2.06 (each s, 3H ꢅ
2, OAc), 1.19, 1.19 (each s, 9H ꢅ 2, OPiv); 13C NMR (A-500, CDCl3) ꢈ 177.91,
177.29, 171.71, 170.21, 169.51 (CꢄO), 135.66 (CHꢄCH2), 129.51, 128.34,

ORDER
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SYNTHESIS OF NEW GLYCOPOLYMERS
137
128.04, 126.50, 116.80 (Ph), 114.09 (CHꢄCH2), 97.00 (C-1), 72.75 (C-5), 70.77
(C-3), 66.18 (C-4), 62.72 (C-6), 49.66 (C-2), 43.34, 38.81, 30.88 (CH2).
Anal. Calcd for C38H50N2O10: C, 65.68; H, 7.24; N, 4.03. Found: C, 65.18;
H, 7.36; N, 3.86.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl 4-O-Acetyl-2-deoxy-
3,6-di-O-pivaloyl-ꢀ-D-arabino-hexopyranoside (24). To a solution of p-(car-
boxyethyl)phenyl glycoside 20 (60 mg, 0.11 mmol) and 1-ethyl-3-(3-dimethy-
laminopropyl)carbodiimide (WSC) (24 mg, 0.12 mmol) in dichloromethane (10
mL), a solution of p-vinylbenzylamine16 (5 mg, 0.15 mmol) in dichloromethane (3
mL) was added dropwise at 0°C, and the reaction mixture was stirred for 1 h until
the disappearance of 20 on TLC with hexane/ethyl acetate (1/2 v/v). The reaction
mixture was diluted with dichloromethane, washed with 10% aq citric acid
solution, brine and water, dried over anhydrous magnesium sulfate, filtered, and
concentrated to give a residue. The remaining residue was purified on a column of
silica gel with hexane/ethyl acetate (1/1 v/v) to afford 24 (56 mg, 76% yield): mp
25
131–132°C (ethanol-hexane); [ꢁ]D ꢃ24.4° (c 1.0, CHCl3); IR (cmꢃ1) 1734
1
(CꢄO), 1644 (CꢄC); H NMR (A-500, CDCl3) ꢈ 7.34, 7.11 (each d, 4H, styryl
phenylene, J ꢄ 8.0 Hz), 7.08, 6.92 (each d, 4H, phenylene, J ꢄ 8.6 Hz), 6.69 (dd,
1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.4 Hz, Jcis ꢄ 10.7 Hz) 5.73 (dd, 1H, Ha, Jgem ꢄ
0.6 Hz), 5.66 (t, 1H, -CONH-), 5.25 (dd, 1H, Hb), 5.14 (dd, 1H, H-1, J1,2eq ꢄ 2.1
Hz, J1,2ax ꢄ 9.4 Hz), 5.05 (ddd, 1H, H-3, J2eq,3 ꢄ 4.9 Hz, J2ax,3 ꢄ 11.6 Hz, J3,4 ꢄ
9.1 Hz), 5.04 (dd, 1H, H-4, J4,5 ꢄ 9.1 Hz), 4.37 (d, 2H, -NHCH2-, JNH,CH2 ꢄ 5.6
Hz), 4.24 (dd, 1H, H-6, J5,6 ꢄ 2.2 Hz, J6,6ꢂ ꢄ 11.9 Hz), 4.12 (dd, 1H, H-6ꢂ, J5,6ꢂ
ꢄ
6.7 Hz), 3.78 (ddd, 1H, H-5), 2.93 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.50 (ddd,
1H, H-2, J2eq,2ax ꢄ 11.3 Hz), 2.46 (t, 2H, -CH2CH2CO-), 2.05 (s, 3H, OAc), 1.98
(ddd, 1H, H-2ax), 1.20, 1.18 (each s, 9H ꢅ 2, OPiv); 13C NMR (A-500, CDCl3) ꢈ
178.26, 177.69, 171.78, 169.53 (CꢄO), 136.36 (CHꢄCH2), 129.36, 116.83,
127.99, 126.50 (Ph), 114.06 (CHꢄCH2), 97.42 (C-1), 72.49 (C-5), 70.12 (C-3),
68.92 (C-4), 63.01 (C-6), 35.90 (C-2), 43.32, 38.73, 30.93 (CH2).
Anal. Calcd for C36H47O9N: C, 67.80; H, 7.43; N, 2.20. Found: C, 68.24; H,
7.72; N, 2.00.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl 4-O-Acetyl-2-deoxy-2
-fluoro-3,6-di-O-pivaloyl-ꢀ-D-mannopyranoside (25). To a solution of p-(pro-
pionic acid)phenyl glycoside 21 (83 mg, 0.15 mmol) and 1-ethyl-3-(3-dimethy-
laminopropyl)carbodiimide (WSC) (32 mg, 0.16 mmol) in dichloromethane (5
mL), a solution of p-vinylbenzylamine16 (25 mg, 0.19 mmol) in dichloromethane
(5 mL) was added dropwise at 0°C, and the reaction mixture was stirred for 20 min
until the disappearance of 21 on TLC with hexane/ethyl acetate (1/3 v/v). The re-
action mixture was diluted with dichloromethane, washed with 10% aq citric acid
solution, brine and water, dried over anhydrous magnesium sulfate, filtered, and
concentrated to give a residue. The remaining residue was purified on a column of
silica gel with hexane/ethyl acetate (1/2 v/v) to afford 25 (62 mg, 61%): mp

ORDER
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138
AKAI ET AL.
25
86–89°C (ether-hexane); [ꢁ]D ꢃ35.2° (c 0.9, CHCl3); IR (cmꢃ1) 1737 (CꢄO)
and 1646 (CꢄC); 1H NMR (A-500, CDCl3) ꢈ 7.34, 7.11 (each d, 4H, styryl pheny-
lene, J ꢄ 7.9 Hz), 7.09, 6.96 (each d, 4H, phenylene, J ꢄ 9.2 Hz), 6.69 (dd, 1H,
-Ph-CHꢄCHaHb, Jtrans ꢄ 17.7 Hz, Jcis ꢄ 11.0 Hz), 5.74 (dd, 1H, Ha, Jgem ꢄ 0.6
Hz), 5.61 (t, 1H, -CONH-), 5.41 (d, 1H, H-4, J3,4 ꢄ J4,5 ꢄ 9.8 Hz), 5.25 (dd, 1H,
Hb), 5.10 (dd, 1H, H-1, J1,2 ꢄ 0.3 Hz, J1,F ꢄ 17.1 Hz), 5.02 (dd, 1H, H-3, J2,3
ꢄ 2.4 Hz, J3,F ꢄ 26.9 Hz), 5.00 (ddd, 1H, H-2, J2,F ꢄ 52.3 Hz), 4.37 (d, 1H, -
NHCH2-, JNH,CH2 ꢄ 5.6 Hz), 4.29 (dd, 1H, H-6, J5,6 ꢄ 2.3 Hz, J6,6ꢂ ꢄ 11.9 Hz),
4.15 (dd, 1H, H-6ꢂ, J5, 6ꢂ ꢄ 6.8 Hz), 3.83 (ddd, 1H, H-5), 2.94 (t, 2H, -CH2CH2
CO-, J ꢄ 7.4 Hz), 2.46 (t, 2H, -CH2CH2CO-), 2.06 (s, 3H, OAc), 1.22, 1.20 (each
s, 9H ꢅ 2, OPiv); 13C NMR (A-500, CDCl3) ꢈ 178.17, 177.61, 171.69, 169.54
(CꢄO), 136.33 (CHꢄCH2), 129.47, 127.97, 126.50, 116.82 (Ph), 114.09
(CHꢄCH2), 96.84 (C-1, J1,F ꢄ 15.5 Hz), 87.01 (C-2, J2,F ꢄ 191.4 Hz), 72.77 (C-
5), 71.40 (C-3, J3,F ꢄ 16.6 Hz), 65.63 (C-4), 62.56 (C-6), 43.30, 38.65, 30.90
(CH2).
Anal. Calcd for C37H45FO9N1: C, 66.65; H, 6.80; N, 2.10. Found: C, 66.50;
H, 6.70; N, 1.95.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl ꢀ-D-Mannopyranoside
(26). To a solution of p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl glycoside
22 (484 mg, 0.69 mmol) in methanol (10 mL), sodium methoxide (1.9M in
methanol solution) was carefully added at pH 10, and the reaction mixture was
stirred for 2 h until the disappearance of 22 on TLC with hexane/ethyl acetate (1/2
v/v). The reaction mixture was neutralized with Dowex 50W-X8 (Hꢉ form) ion-
exchange resin, filtered, and concentrated to afford 26 (289 mg, 94% yield): mp
123–126°C (methanol); [ꢁ]D25 ꢃ26.8° (c 0.7, MeOH); IR (cmꢃ1) 3322 (OH), 1644
(CꢄC); 1H NMR (A-500, d6-DMSO) ꢈ 8.23 (t, 1H, NH), 7.36, 7.12 (each d, 4H,
styryl phenylene, Hb, Jtrans ꢄ 17.7 Hz, Jcis ꢄ 11.0 Hz), 5.75 (dd, 1H, Ha, Jgem
ꢄ 0.9 Hz), 5.22 (dd, 1H, Hb), 5.22 (s, 1H, H-1), 4.24 (d, 2H, -NHCH2-, JNH,CH2
ꢄ 5.1 Hz), 3.88 (d, 1H, H-2, J2,3 ꢄ 3.3 Hz), 3.73 (dd, 1H, H-3, J3,4 ꢄ 11.3 Hz),
3.51–3.41 (m, 3H, H-4, H-6, and H-6ꢂ), 3.32 (br s, 4H, OH), 3.24 (ddd, 1H, H-5,
J
4,5 ꢄ 8.8 Hz, J5,6 ꢄ 2.1 Hz, J5,6ꢂ ꢄ 6.1 Hz), 2.81 (t, 2H, -CH2CH2CO-, J ꢄ 7.8
Hz), 2.42 (t, 2H, -CH2CH2CO-); 13C NMR (A-500, d6-DMSO) ꢈ 171.24 (CꢄO),
136.46, 135.52, 134.20, 128.94, 127.25, 125.79 (Ph), 136.22 (CHꢄCH2), 113.46
(CHꢄCH2), 97.84 (C-1), 77.43 (C-2), 73.42 (C-3), 70.54 (C-4), 66.78 (C-5), 60.99
(C-6), 41.70, 37.16, 30.22 (CH2).
Anal. Calcd for C24H29O7N: C, 65.00; H, 6.59; N, 3.16. Found: C, 64.94; H,
6.48; N, 2.99.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl 2-Acetamido-2-deoxy-
ꢀ-D-mannopyranoside (27). To a solution of p-[2-[N-(p-vinylbenzyl)car-
bamoyl]ethyl]phenyl glycoside 23 (478 mg, 0.69 mmol) in methanol (30 mL),
sodium methoxide (1.9M in methanol solution) was carefully added at pH 10, and
the reaction mixture was stirred for 2 h until the disappearance of 23 on TLC with
hexane/ethyl acetate (1/4 v/v). The reaction mixture was neutralized with Dowex

ORDER
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SYNTHESIS OF NEW GLYCOPOLYMERS
139
50W-X8 (Hꢉ form) ion-exchange resin, filtered, and concentrated to afford 27
(333 mg, quantitatively): mp 99–102°C (methanol); [ꢁ]D25 ꢃ67.8° (c 0.8, MeOH);
IR (cmꢃ1) 3304 (OH), 1656 (CꢄC); 1H NMR (A-500, d6-DMSO) ꢈ 8.29 (t, 1H, -
CONH-), 7.42 (d, 1H, NHAc, JNH,2 ꢄ 9.8 Hz), 7.37, 7.12 (each d, 4H, styryl
phenylene, J ꢄ 8.3 Hz), 7.09, 6.86 (each d, 4H, phenylene, J ꢄ 8.5 Hz), 6.70 (dd,
1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.4 Hz, Jcis ꢄ 10.9 Hz), 5.78 (dd, 1H, Ha, Jgem
ꢄ 0.6 Hz ), 5.21 (dd, 1H, Hb,), 5.19 (d, 1H, H-1, J1,2 ꢄ 1.5 Hz), 4.47 (ddd, 1H, H-
2, J2,3 ꢄ 1.8 Hz), 4.22 (d, 2H, -NHCH2-, JNH,CH2 ꢄ 5.1 Hz), 3.74 (dd, 1H, H-3, J3,4
ꢄ 11.6 Hz), 3.57 (dd, 1H, H-6, J6,6ꢂ ꢄ 9.2 Hz), 3.54 (dd, 1H, H-6ꢂ, J6ꢂ,5 ꢄ 6.4 Hz),
3.34 (t, 1H, H-4, J4,5 ꢄ 9.7 Hz), 3.29 (ddd, 1H, H-5, J5,6 ꢄ 4.6 Hz), 3.29 (br s, 4H,
OH), 2.77 (t, 2H, -CH2CH2CO-, J ꢄ 7.9 Hz), 2.40 (t, 2H, -CH2CH2CO-), 1.93 (s,
3H, NHAc); 13C NMR (A-500, d6-DMSO) ꢈ 171.27, 169.97 (CꢄO), 129.07,
127.37, 125.95, 116.06 (Ph), 134.51 (CHꢄCH2), 113.75 (CHꢄCH2), 96.94 (C-1),
77.87 (C-5), 73.97 (C-3), 66.97 (C-4), 61.04 (C-6), 52.35 (C-2), 41.70, 37.11,
30.22 (CH2), 22.94 (CH3).
Anal. Calcd for C26H32N2O7: C, 64.45; H, 6.66; N, 5.78. Found: C, 64.34; H,
6.53; N, 5.84.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl ꢀ-D-Arabino-hexopyra-
noside (28). To a solution of p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl
glycoside 24 (416 mg, 0.65 mmol) in methanol (18 mL), sodium methoxide (1.9M
in methanol solution) was carefully added at pH 10, and the reaction mixture was
stirred for 2 h until the disappearance of 24 on TLC with hexane/ethyl acetate (1/1
v/v). The reaction mixture was neutralized with Dowex 50W-X8 (Hꢉ form) ion-
exchange resin, filtered, and concentrated to afford 28 (279 mg, quantitatively): mp
171–172°C (ethanol-hexane); [ꢁ]D ꢃ28.6° (c 0.6, DMSO); IR (cmꢃ1) 3298
25
1
(OH), 1644 (CꢄC); H NMR (A-500, d6-DMSO) ꢈ 8.28 (t, 1H, -CONH-), 7.37,
7.09 (each d, 4H, styryl phenylene, J ꢄ 8.3 Hz), 7.11, 6.90 (each d, 4H, phenylene,
J ꢄ 8.5 Hz), 6.69 (dd, 1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.7 Hz, Jcis ꢄ 11.0 Hz), 5.78
(dd, 1H, Ha, Jgem ꢄ 0.9 Hz), 5.21 (dd, 1H, Hb), 5.16 (dd, 1H, H-1, J1,2eq ꢄ 2.2 Hz,
J
J
1,2ax ꢄ 9.7 Hz), 4.22 (d, 2H, -NHCH2-, JNH,CH2 ꢄ 5.8 Hz), 3.68 (ddd, 1H, H-6,
5,6 ꢄ 2.1 Hz, J6,6ꢂ ꢄ 11.9 Hz), 3.50 (ddd, 1H, H-6ꢂ, J5,6 ꢄ 6.0 Hz), 3.48 (dd, 1H,
H-4, J5,4 ꢄ J5,6 ꢄ 9.5 Hz), 3.54 (dd, 1H, H-6 ꢂ, J5,6ꢂ ꢄ 6.4 Hz), 3.34 (t, 1H, H-4,
4,5 ꢄ 9.7 Hz), 3.31 (br s, 3H, OH), 3.23 (ddd, 1H, H-5), 3.05 (ddd, 1H, H-3, J2eq,3
J
ꢄ 5.2 Hz, J2ax,3 ꢄ 11.6 Hz), 2.77 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.40 (t, 2H,
-CH2CH2CO-), 2.14 (ddd, 1H, H-2ax, J2ax,2eq ꢄ 12.3 Hz), 1.55 (ddd, 1H, H-2eq);
13C NMR (A-500, d6-DMSO) ꢈ 171.25 (CꢄO), 136.35 (CHꢄCH2), 129.05,
127.34, 125.93, 115.87 (Ph), 113.72 (CHꢄCH2), 96.73 (C-1), 77.18 (C-5), 71.21
(C-3), 70.38 (C-4), 60.82 (C-6), 41.67 (NHCH2), 39.50 (C-2), 37.15, 30.2 (CH2).
Anal. Calcd for C24H29O6N: C, 67.80; H, 6.84; N, 3.28. Found: C, 67.17; H,
7.03; N, 3.31.
p-[2-[N-(p-Vinylbenzyl)carbamoyl]ethyl]phenyl 2-Deoxy-2-fluoro-ꢀ-D-
mannopyranoside (29). To a solution of p-[2-[N-(p-vinylbenzyl)carbamoyl]-
ethyl]phenyl glycoside 25 (37 mg, 0.06 mmol) in methanol (1 mL), sodium

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AKAI ET AL.
methoxide (1.9M in methanol solution, 1 mL) was carefully added at pH 10, and
the reaction mixture was stirred for 2 h until the disappearance of 25 on TLC with
hexane/ethyl acetate (1/2 v/v). The reaction mixture was neutralized with Dowex
50W-X8 (Hꢉ form) ion-exchange resin, filtered, and concentrated to afford 29 (25
mg, quantitatively): mp 185–186°C (ether-hexane); [ꢁ]D25 ꢃ35.2° (c 0.2, DMSO);
IR (cmꢃ1) 3280 (OH), 1641 (CꢄC); 1H NMR (A-500, d6-DMSO) ꢈ 8.30 (t, 1H, -
CONH-), 7.38, 7.12 (each d, 4H, styryl phenylene, J ꢄ 7.9 Hz), 7.12, 6.92 (each d,
4H, phenylene, J ꢄ 8.6 Hz), 6.69 (dd, 1H, -Ph-CHꢄCHaHb, Jtrans ꢄ 17.8 Hz, Jcis
ꢄ 11.0 Hz), 5.78 (dd, 1H, Ha, Jgem ꢄ 0.6 Hz), 5.28 (dd, 1H, H-1, J1,2 ꢄ 0.3 Hz,
J1,F ꢄ 19.5 Hz), 5.21 (dd, 1H, Hb), 4.72 (ddd, 1H, H-2, J2,F ꢄ 52.5 Hz), 4.22 (d,
2H, -NHCH2-, JNH,CH2 ꢄ 4.9 Hz), 3.70 (dd, 1H, H-6, J6,6ꢂ ꢄ 11.7 Hz), 3.57 (ddd,
1H, H-3, J2,3 ꢄ 2.4 Hz, J3,F ꢄ 31.1 Hz), 3.47 (dd, 1H, H-6ꢂ, J6ꢂ,5 ꢄ 5.7 Hz), 3.40
(dd, 1H, H-4, J3,4 ꢄ J4,5 ꢄ 9.3 Hz), 3.29 (ddd, 1H, H-5, J5,6 ꢄ 1.2 Hz), 3.29 (br s,
3H, OH), 2.78 (t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.40 (t, 1H, -CH2CH2CO-); 13
C
NMR (A-500, d6-DMSO) ꢈ 171.24 (CꢄO), 136.34 (CHꢄCH2), 129.13, 127.35,
125.95, 115.70 (Ph), 113.73 (CHꢄCH2), 95.75 (C-1, J1,F ꢄ 14.4 Hz), 90.53 (C-2,
J2,F ꢄ 185.2 Hz), 77.47 (C-5), 71.70 (C-3, J3,F ꢄ 17.6 Hz), 66.69 (C-4), 60.57 (C-
6), 41.69, 37.13, 30.21 (CH2).
Anal. Calcd for C24H28FO6N: C, 64.70; H, 6.34; N, 3.14. Found: C, 64.59; H,
6.37; N, 2.86.
Poly[p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl ꢀ-D-mannopyra-
noside] (30). To a solution of 26 (269 mg, 0.61 mmol) in DMSO (1.0 mL), 2,2ꢂ-
azobisisobutyronitrile (4.0 mg, 0.02 mmol) was added. The reaction mixture was
set in a sealed tube, degassed with argon, and kept at 65°C in an oil bath for 24 h.
The reaction mixture was poured into stirred acetone, and the precipitate separated
using a glass filter to give 30 (260 mg, 97% yield): IR (cmꢃ1) 3340 (OH), 1644
(CꢄO); 13C NMR (A-500, d6-DMSO) ꢈ 171.24 (CꢄO), 128.58, 115.76 (Ph),
126.58 (-CH-CH2-), 97.78 (C-1), 77.35 (C-2), 73.41 (C-3), 70.45 (C-4), 66.77 (C-
5), 60.99 (C-6), 41.70, 40.40, 37.24, 30.51 (CH2).
Poly[p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl 2-acetamido-2-de-
oxy-ꢀ-D-mannopyranoside] (31). To a solution of 27 (204 mg, 0.42 mmol) in
DMSO (1.0 mL), 2,2ꢂ-azobisisobutyronitrile (4.0 mg, 0.02 mmol) was added. The
reaction mixture was set in a sealed tube, degassed with argon, and kept at 65°C in
an oil bath for 24 h. The reaction mixture was poured into stirred acetone, and the
precipitate separated using a glass filter to give 31 (171 mg, 84% yield): IR (cmꢃ1
)
3430 (OH), 1644 (CꢄO); 13C NMR (A-500, d6-DMSO) ꢈ 170.19 (CꢄO), 128.95,
116.06 (Ph), 126.58 (-CH-CH2-), 96.85 (C-1), 77.75 (C-5), 71.97 (C-3), 66.91 (C-
4), 61.02 (C-6), 52.38 (C-2), 37.22, 30.63, 30.33, 26.77 (CH2), 22.92 (CH3).
Poly[p-[2-(N-(p-vinylbenzyl)carbamoyl)ethyl]phenyl ꢀ-D-arabino-hex-
opyranoside] (32). To a solution of 28 (234 mg, 0.55 mmol) in DMSO (2.0 mL),
2,2ꢂ-azobisisobutyronitrile (3.0 mg, 0.015 mmol) was added. The reaction mixture
was set in a sealed tube, degassed with argon, and kept at 65°C in an oil bath for

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SYNTHESIS OF NEW GLYCOPOLYMERS
141
24 h. The reaction mixture was poured into stirred acetone, and the precipitate sep-
arated using a glass filter to give 32 (202 mg, 86% yield): IR (cmꢃ1) 3412 (OH),
1647 (CꢄO); 13C NMR (A-500, d6-DMSO) ꢈ 171.48 (CꢄO), 128.95, 115.87 (Ph),
126.36 (-CH-CH2-), 96.73 (C-1), 77.10 (C-5), 71.18 (C-), 70.39 (C-4), 60.80 (C-
6), 39.34 (C-2), 37.27, 30.63, 30.33 (CH2).
Poly[p-[2-[N-(p-vinylbenzyl)carbamoyl]ethyl]phenyl 2-deoxy-2-fluoro-
ꢀ-D-mannopyranoside] (33). To a solution of 29 (229 mg, 0.514 mmol) in
DMSO (1.0 mL), 2,2ꢂ-azobisisobutyronitrile (4.0 mg, 0.02 mmol) was added. The
reaction mixture was set in a sealed tube, degassed with argon, and kept at 65°C in
an oil bath for 24 h. The reaction mixture was poured into stirred acetone, and the
precipitate separated using a glass filter to give 33 (128 mg, 56% yield): IR (cmꢃ1
)
3448 (OH), 1638 (CꢄO); 13C NMR (A-500, d6-DMSO) ꢈ 171.37 (CꢄO), 129.03,
115.72 (Ph), 127.76 (-CH-CH2-), 95.71 (C-1, J1,F ꢄ 14.5 Hz), 90.51 (C-2, J2,F ꢄ
184.1 Hz), 77.40 (C-5), 71.76 (C-3, J3,F ꢄ 18.6 Hz), 66.68 (C-4), 60.58 (C-6),
40.09, 37.25, 30.65, 30.30 (CH2).
Benzyl 3-(p-hydroxyphenyl)propionate (34). To a solution of 3-(p-hy-
droxyphenyl)propionic acid (500 mg, 3.0 mmol) and potassium hydrogencarbon-
ate (600 mg, 6.0 mmol) in N,N-dimethylformamide (10 mL), benzyl bromide (0.4
mL, 3.39 mmol) was added dropwise at 0°C and the reaction mixture was stirred
for 12 h at rt until the disappearance of starting compound on TLC with
hexane/ethyl acetate (4/1 v/v). The reaction mixture was poured into a saturated aq
NaHCO3 solution, extracted with ethyl acetate, washed with brine and water, dried
over anhydrous magnesium sulfate, filtered, and concentrated to give a residue.
The remaining residue was purified on a column of silica gel with hexane/ethyl ac-
etate (4/1 v/v). The yield of 34 was quantitative (765 mg): IR (cmꢃ1) 3406 (OH),
1713 (CꢄO); 1H NMR (EX-90, CDCl3) ꢈ 7.34–7.32 (m, 5H, -CH2Ph), 7.04, 6.73
(each d, 4H, phenylene, J ꢄ 8.6 Hz), 5.33 (m, 1H, OH), 5.10 (s, 2H, -CH2Ph), 2.85
(t, 2H, -CH2CH2CO-, J ꢄ 7.8 Hz), 2.68 (t, 2H, -CH2CH2CO-).
Anal. Calcd for C16H16O3: C, 74.98%; H, 6.29%. Found: C, 74.49%; H,
6.44%.
Enzyme-linked lectin assay (ELLA)23–25 using Concanavaline A and the
synthetic glycopolymers as inhibitors. Nunclon microtiter plates (Nuc439454)
were coated with soybean lectin (SBA) (Honen Co. Ltd.: 03907) at 100 ꢇL/well of
2-fold serial dilution in 50 ꢇg/L Tris-HCl buffer (pH 7.3), containing 0.15 M NaCl,
and 0.1% (v/v) Tween 20 (PBST) and incubated overnight at 4°C. The plates were
then washed with 50 mM Tris-HCl buffer, containing 0.15M NaCl, and 0.1%
Tween 20, and blocked with 400 ꢇL of 1% (v/v) BSA in PBS for 1 h at rt and then
the plate was washed three times. Each inhibitor, methyl ꢁ-D-mannopyranoside,
methyl ꢁ-D-glucopyranoside, and synthesized glycopolymers (6, 30, 31, 32, 33)
(50% (v/v) DMSO/H2O), was added to biotin labeled-Con A (Honen Co. Ltd.:
90408) (10 ng/mL in washing solution containing 0.25% (v/v) gelatine). After stor-
ing for 60 min at rt, 100 ꢇL of the above inhibitor solutions were transferred to the

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AKAI ET AL.
SBA-coated plates and incubated for 60 min at rt. After washing three times as
mentioned above, 100 ꢇL of horseradish peroxidase labeled-streptavidin (Fu-
nakoshi Co. Ltd.: Vector SA-5004) (1 ꢇg/mL in washing solution) was added, and
then incubated for 30 min at rt. After washing three times as mentioned above, 100
ꢇL of color-producing reagent (Funakoshi Co. Ltd.: 50507600) was added. After
30 min at rt, the reaction was stopped with 100 ꢇL of 2 mM NaN3 solution, and the
adsorbance of each well at 450 relative to 600 nm was determined on a micro plate
reader (Tosho Co. Ltd.: MPR-A4i).
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Received September 19, 2000
Accepted January 22, 2001

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