Chemical synthesis of the Pseudomonas aeruginosa O11 O-antigen trisaccharide based on neighboring electron-donating effect

Article abstract of DOI:10.1080/07328303.2020.1839479

Pseudomonas aeruginosa O11 O-antigen is immunologically active but an exact protective epitope has not yet been identified. Synthesis of O11 O-antigen trisaccharide is of importance for identifying the epitopes. Here, neighboring electron-donating effects are keys to enhance the nucleophilicity of the C3 hydroxyl groups of D- and L-fucosamines, to facilitate the efficient synthesis of the trisaccharide. The disarmed peracetylated glycosyl donor with low glycosylation reactivity and glycosyl trifluoroacetimidate with good stability allowed for the glycosylation under mild conditions. The C6 nucleophilic tosylate substitution of D-galactose with iodine was found to be dependent on the steric effect of the axial C4.

Full text of DOI:10.1080/07328303.2020.1839479

Journal of Carbohydrate Chemistry
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/lcar20
Chemical synthesis of the Pseudomonas aeruginosa
O11 O-antigen trisaccharide based on neighboring
electron-donating effect
Chunjun Qin , Zhonghua Liu , Meiru Ding , Juntao Cai , Junjie Fu , Jing Hu ,
Peter H. Seeberger & Jian Yin
To cite this article: Chunjun Qin , Zhonghua Liu , Meiru Ding , Juntao Cai , Junjie Fu , Jing Hu ,
Peter H. Seeberger & Jian Yin (2020): Chemical synthesis of the Pseudomonasꢀaeruginosa O11
O-antigen trisaccharide based on neighboring electron-donating effect, Journal of Carbohydrate
Chemistry, DOI: 10.1080/07328303.2020.1839479
To link to this article: https://doi.org/10.1080/07328303.2020.1839479
Published online: 30 Oct 2020.
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JOURNAL OF CARBOHYDRATE CHEMISTRY
https://doi.org/10.1080/07328303.2020.1839479
Chemical synthesis of the Pseudomonas aeruginosa
O11 O-antigen trisaccharide based on neighboring
electron-donating effect
a
ꢀ
a
ꢀ
a
a,b
a
Chunjun Qin , Zhonghua Liu , Meiru Ding , Juntao Cai , Junjie Fu ,
a,c
b
a
Jing Hu , Peter H. Seeberger , and Jian Yin
a
Key Laboratory of Carbohydrate Chemistry and Biotechnology, Ministry of Education, School of
b
Biotechnology, Jiangnan University, Wuxi, China; Department of Biomolecular Systems, Max-
Plank Institute of Colloids and Interfaces, Potsdam, Germany; Wuxi School of Medicine, Jiangnan
c
University, Wuxi, China
ABSTRACT
ARTICLE HISTORY
Pseudomonas aeruginosa O11 O-antigen is immunologically
active but an exact protective epitope has not yet been iden-
tified. Synthesis of O11 O-antigen trisaccharide is of import-
ance for identifying the epitopes. Here, neighboring electron-
donating effects are keys to enhance the nucleophilicity of
the C3 hydroxyl groups of D- and L-fucosamines, to facilitate
the efficient synthesis of the trisaccharide. The disarmed pera-
cetylated glycosyl donor with low glycosylation reactivity and
glycosyl trifluoroacetimidate with good stability allowed for
the glycosylation under mild conditions. The C6 nucleophilic
tosylate substitution of D-galactose with iodine was found to
be dependent on the steric effect of the axial C4.
Received 7 September 2020
Accepted 16 October 2020
KEYWORDS
Chemical synthesis;
Pseudomonas aeruginosa;
O-antigen; protecting
group; glycosylation
Introduction
Pseudomonas aeruginosa, a notorious opportunistic human nosocomial
[
1]
pathogen, causes acute infections such as bacteremia and pneumonia.
Pseudomonas aeruginosa infects about 51,000 patients in the US each year
[
2,3]
with a mortality rate of 5%.
In 2017, P. aeruginosa was ranked as a top
priority pathogen in the WHO antibiotic-resistant bacteria priority list,
[
4]
highlighting the urgent need for vaccines. Few experimental vaccines
have reached clinical evaluation [e.g. lipopolysaccharide (LPS), flagella] but
[
5]
no vaccines have been licensed yet.
Vaccine development has focused on the 20 serotypes of the LPS O-anti-
[6]
gen of P. aeruginosa. The O-antigen of P. aeruginosa serotype O11, the
second most prevalent serotype in critically ill patients, has drawn the most
[2,6,7]
attention.
The O11 O-antigen structure has been elucidated to consist of
CONTACT Jian Yin
jianyin@jiangnan.edu.cn
Key Laboratory of Carbohydrate Chemistry and
Biotechnology, Ministry of Education, School of Biotechnology, Jiangnan University, Wuxi, China.
ꢀ
These authors contributed equally to this work.
ß 2020 Taylor & Francis Group, LLC

2
C. QIN ET AL.
a trisaccharide repeating unit, [!2)-b-D-Glcp-(1!3)-a-L-FucpNAc-(1!3)-
[8]
b-D-FucpNAc-(1!]. Notably, the a-L-FucNAc-(1!3)-D-FucNAc unit is
also a component of the capsular polysaccharides (CPS) of Staphylococcus
[
9]
[10]
aureus type 5 and 8, Acinetobacter baumannii type K12,
K73.
K13, and
A heptavalent P. aeruginosa O-antigen vaccine (serotypes O1, O2,
O3, O5, O6, O10, and O11) induced a robust serotype-specific antibody
[
11]
[
12]
response in mice and rabbits.
mutant strains expressing the P. aeruginosa O11 O-antigen protected mice
from acute P. aeruginosa infection.
were limited by side effects associated with contaminants. While the glu-
cose residue proved to be essential for the epitopes of the O11 O-antigen,
In addition, the attenuated Salmonella
[
7,13]
However, these experimental vaccines
[6]
[14]
it remains to be determined whether the a-L-FucNAc-D-FucNAc unit is
immunogenic. Synthetic oligosaccharides offer an attractive means to procure
vaccines free of contaminants. Well-defined oligosaccharides can facilitate
[
15]
epitope mapping as an essential step for vaccine design.
have been devoted to the synthesis of rare deoxy aminosugars as a basis for
the construction of bacterial glycans.
Intense efforts
[
16–27]
The outcome of glycosylation
reactions relies on the reactivities of the glycosyl donor and acceptor, that
[
28–31]
can be tuned by protecting group strategy based on conformational
[
32–35]
and electronic effects,
and assembly sequence planning based on steric
Recently, the Kulkarni group reported the first synthesis of the
P. aeruginosa O11 trisaccharide O-antigen based on protecting group pattern
[
36–40]
effect.
[18]
tuning of the reactivities of glycosyl donors and acceptors (Fig. 1).
Figure 1. Previous synthesis of the P. aeruginosa O11 O-antigen trisaccharide via a regioselec-
tive glycosylation.

JOURNAL OF CARBOHYDRATE CHEMISTRY
3
The inefficient glycosylation at O3 of acceptor A1, a regioselective glycosyla-
tion with the 3,4-diol A2 smoothly afforded the 1!3 coupled trisaccharide
T2, indicating that the protecting group pattern of 4-OH dramatically influ-
ences the reactivity of 3-OH in L-fucosamine. The syntheses of S. aureus
type 5 and 8 CPS trisaccharides taught lessons on the successful glycosylation
at O3 of D- and L-fucosamines. D-Fucosamine acceptors with three protect-
[
17,41–44]
[45]
ing group patterns 2-N -4-OBn-D-Fuc,
and 2-NHTCA-4-OBn-D-Fuc,
2-NHTroc-4-OBn-D-Fuc
3
[18]
have been utilized to enhance the nucleo-
philicity of 3-OH group. Demchenko employed a 3-OH L-fucosamine
acceptor bearing a 2-azido group and 4-O-benzyl group to smoothly install
[
43]
the (1!3) glycosidic bond.
Replacement of an electron-withdrawing ace-
tyl group by an electron-donating 2-naphthylmethyl group at the 3-hydroxyl
group significantly increased the reactivity of 4-OH in the L-fucosamine
acceptor in the context of another synthesis.
[
46]
Here, we report a synthesis
of the conjugation-ready P. aeruginosa O11 O-antigen trisaccharide. The key
to efficient glycosylation is the use of the neighboring electron-donating
effect to enhance the nucleophilicity of the glycosyl acceptor. Facile synthetic
routes to D-fucosamine and L-fucosamine building blocks from D-galactose
and L-fucose are disclosed as well.
Results and discussion
An aminopropyl linker was placed at the reducing end of synthetic trisac-
charide 1 for conjugation to carrier proteins or immobilization on glycan
array surfaces (Fig. 2). Since the D-glucose residue in the O11 O-antigen is
[
14]
an essential part of the antigenic epitope,
trisaccharide 1 assembly
started from the nonreducing end to facilitate the preparation of disacchar-
ide containing b-D-glucose residue. Peracetylated glucose 5, the most
accessible building block, was chosen to enable the stereoselective forma-
tion of the b-glycosidic bond. D-Fucosamine 4 and L-fucosamine 6 were
Figure 2. Retrosynthetic analysis of trisaccharide 1.

4
C. QIN ET AL.
identified in retrosynthetic analysis, the electron-donating C2 azide and C4
benzyl ether were designed to increase the nucleophilicity of the adjacent
C3 hydroxyl group. Particularly, the nonparticipating C2 azide of the L-
fucosamine 6 would be beneficial for the stereoselective formation of the
1,2-cis-glycosidic bond. Various aminosugars have been prepared by chem-
ical methods, including nucleophilic substitution suitable for amination at
[
19,21]
each position of the sugar ring,
nosugars.
and glycal addition specific to 2-ami-
[
43,46]
Glycal addition can simultaneously introduce a C1 protect-
ing group and a C2 azide into peracetylated glycal, significantly improving
the synthesis efficiency. Here, fucal addition was adapted to introduce a C2
azide into D-fucosamine 4 and L-fucosamine 6. To shorten the reaction
steps, an O1-allyl group in 6 was to be placed via fucal addition instead of
conventional acid-catalyzed O-glycosylation. In addition to the synthesis
procedure, the large-scale preparation of 6-deoxy aminosugars that are rare
[
46,47]
in nature,
has to take the cost of starting materials into account.
Thus, L-fucose and D-galactose were chosen as starting materials.
[
48]
D-Galactal 7
fucosamine 4 (Scheme 1). Azidoselenation of 7 gave the C2 azide derivative
, which was converted to 11 by deacetylation, benzylidene acetal forma-
derived from D-galactose served for the synthesis of D-
8
tion, and O3-acetylation. A regioselective reductive ring opening of the 4,6-
O-benzylidene acetal of 11 using trimethylsilyl trifluoromethanesulfonate
(
TMSOTf)/borane tetrahydrofuran complex (BH ꢁTHF) afforded the 4-O-
3
benzyl-6-hydroxy derivative 12 in 81% yield. Tosylation of 12 delivered
-O-tosyl derivative 13 as a substrate for deoxygenation at C6. Since the
6
presence of C2 azide precludes the use of strong reducing agents like lith-
ium aluminum hydride, the iodination/reduction strategy that previously
[
46]
worked well for glucose stereoisomer
of 13 was employed. However, the
treatment of 13 with tetrabutylammonium iodide (TBAI) or NaI at high
ꢂ
temperatures (80–100 C) failed to produce 6-iodide 14.
In view of the steric hindrance effect of axial C4-OBn group of 13, 6-O-
tosyl derivative 15 derived from 9 by regioselective tosylation was employed
Scheme 1. Attempt to prepare 6-iodo-D-galactose 14.

JOURNAL OF CARBOHYDRATE CHEMISTRY
5
Scheme 2. Synthesis of D-fucosamine 4.
(Scheme 2). Nucleophilic tosylate substitution with NaI in refluxing buta-
none and subsequent reduction with sodium cyanoborohydride furnished
D-fucosamine 16 in 54% overall yield. The tin-mediated regioselective 4-
methoxybenzylation at O3 of diol 16 was followed by O4 benzylation to
deliver 18 in good yield. Considering the partial cleavage of 4-methoxyben-
[
46]
zyl ether (PMB) during acid-mediated glycosylation reactions,
3-O-acetyl
derivative 19 was obtained by oxidative removal of the PMB group and
subsequent acetylation in 82% overall yield. For the insertion of an amino-
propyl linker, the hydrolyzed product of 19 was converted to donor 20 fol-
lowed by TMSOTf-catalyzed glycosylation with N-Bn-N-Cbz-3-
ꢂ
aminopropan-1-ol in DCM at ꢃ40 C to give 21. Deacetylation of 21
afforded D-fucosamine 4.
The synthesis of the L-fucosamine 6 started from L-fucose via known L-
[
46]
fucal 22
(Scheme 3). Azidonitration of 22 with sodium azide and ceric
ꢂ
ammonium nitrate (CAN) at ꢃ15 C and subsequent treatment with
sodium and allyl alcohol gave 23 in 67% overall yield. The tin-mediated
regioselective naphthylmethylation at O3 of the diol 23 was followed by O4
benzylation to afford 25 in good yield. Removal of 3-ONap with DDQ con-
verted 25 to 6 in 93% yield.
Assembly of trisaccharide started from the nonreducing to the reducing
[
49]
end (Scheme 3). The union of glucosyl donor 5
and L-fucosamine
acceptor 6 in the presence of TMSOTf at room temperature furnished
desired disaccharide 26 in 88% yield and complete b-selectivity (the
3
anomeric proton of the donor residue: J
¼ 7.7 Hz, d
¼ 4.77 ppm).
H1/H2
H-1
Notably, the relatively low glycosylation reactivity of disarmed peracetylated
glycosyl donor 5 required higher reaction temperatures than that of

6
C. QIN ET AL.
Scheme 3. Synthesis of trisaccharide 1.
ꢂ
common trichloroacetimidate glycosylation conditions (ꢃ70 to ꢃ20 C),
facilitating the operation of the glycosylation reaction. The removal of the
anomeric allyl group with PdCl gave hemiacetal 27, that was transformed
2
[
50]
to Yu donor 3 upon trifluoroacetimidation
in 79% overall yield.
TMSOTf-catalyzed glycosylation of D-fucosamine acceptor 4 with Yu
donor 3 in a blended solvents system including DCM, diethyl ether, and
thiophene at room temperature lead to desired trisaccharide 2 in 84% yield
and complete a-selectivity. The a-configuration of the newly formed glyco-
sidic bond in 2 was confirmed by the anomeric proton JC,H coupling of
171 Hz. The exclusive a-glycosylation can be attributed to the nonpartici-
pating C2 azide group in donor 3, anomeric, and solvent effects. The util-
ꢂ
ization of glycosyl trifluoroacetimidate 3, generally activated at 0 C to
room temperature,
[
37,51]
helped to perform the glycosylation reaction under
mild conditions. The protecting group patterns of L-fucosamine acceptor 6
and D-fucosamine acceptor 4 served well for enhancing their nucleophilic-
ity. Subsequent azide reduction and N-acetylation of 2 using AcSH/pyridine
afforded the corresponding acetamide derivative 28 in 96% yield. Finally,
global deprotection of 28 with deacetylation and subsequent Pd/C hydro-
1
genation afforded target trisaccharide 1 in 95% overall yield. The H and
13
[18]
C NMR data of 1 is identical to the earlier reported data.

JOURNAL OF CARBOHYDRATE CHEMISTRY
7
Conclusion
Chemical synthesis of P. aeruginosa O11 O-antigen trisaccharide 1 was
achieved. Rare D- and L-fucosamine acceptors 4 and 6, designed based on
the neighboring electron-donating effect, were prepared from D-galactose
and L-fucose starting from glycal addition. The nucleophilic tosylate substi-
tution at C6 of the D-galactose derivative containing an azido group for C6
deoxygenation was largely dependent upon the steric effect of the axial C4
position. The corresponding 6-iodine-D-galactose derivative was success-
fully obtained from 4-OH tosylate 15, but not from 4-OBn tosylate 13. The
efficient assembly of trisaccharide 1 indicated that the electron-donating C2
azides and C4 benzyl ethers of L-fucosamine acceptor 6 and D-fucosamine
acceptor 4 are important for enhancing the nucleophilicity of the adjacent
C3 hydroxyl groups. Moreover, the disarmed peracetylated glycosyl donor
5
with relatively low glycosylation reactivity and glycosyl trifluoroacetimi-
date 3 (Yu donor) with good stability allowed for the glycosylation under
mild conditions. An aminopropyl linker installed at the reducing end of 1
enables the further conjugation or immobilization, which may facilitate
immunological evaluation of P. aeruginosa O11 O-antigen. The design of
glycosyl acceptor based on neighboring electron-donating effect will be
valuable for the syntheses of other complex glycans.
Experimental section
Materials and methods
Commercial reagents and solvents (analytical grade) were used without fur-
ther purification, unless otherwise stated. The anhydrous solvents used in
the reactions were obtained from an MBraun MB-SPS 800 Dry Solvent
System. Analytical TLC was performed on silica gel 60-F254 precoated on
glass plate. Spots were visualized with sugar stain (0.1% (v/v) 3-methoxy-
phenol, 2.5% (v/v) sulfuric acid in EtOH), CAM stain (5% (w/v) ammo-
nium molybdate, 1% (w/v) cerium(II) sulfate, and 10% (v/v) sulfuric acid
in water) dipping solutions. The normal phase column chromatography
was performed on silica gel (200–300 mesh). Size exclusion chromatog-
V
R
1
raphy (SEC) was performed using Sephadex LH-20 (GE Healthcare). H,
C, and two-dimensional NMR spectra were recorded on a Bruker
13
ꢂ
Ultrashield Plus 400 MHz spectrometer at 25 C. Optical rotations (OR)
were measured with a Schmidt & Haensch UniPol L 1000 at 589 nm and a
concentration (c) expressed in g/100 mL. High-resolution mass spectrom-
etry was performed on an Agilent 6220 ESI-TOF mass spectrometer. IR
spectra were recorded on Thermo Fisher Scientific Nicolet iS5
spectrometer.

8
C. QIN ET AL.
Synthetic procedure for trisaccharide 1
Phenyl 2-azido-3,4,6-tri-O-acetyl-2-deoxy-1-seleno-a-D-galactopyranoside
[
48]
(
(
7
8). D-Galactal 7
(2.0 g, 7.35 mmol) was dissolved in anhydrous DCM
ꢂ
35 mL) and cooled to ꢃ30 C under argon. Diphenyl diselenide (2.3 g,
.37 mmol), (diacetoxyliodo) benzene (BAIB) (2.4 g, 7.45 mmol) and trime-
thylsilyl azide (1.8 mL, 13.69 mmol) were added. The solution was then
allowed to warm to room temperature for 3 h. After the complete conver-
sion of the starting material, the solution was extracted with satd. aq.
NaHCO (3 ꢄ 20 mL), combined the organic layer and dried over Na SO .
3
2
4
The solvent was removed under vacuum and the residue was purified by
silica gel column chromatography (petroleum ether: ethyl acetate 6: 1 v/v)
2
0
ꢂ
to give compound 8 (2.5 g, 5.32 mmol, 72%). [a]D ¼ 931.7 (c ¼ 1.00,
1
CHCl ); H NMR (400 MHz, CDCl ) d ¼ 7.78 ꢃ 7.11 (m, 5H, Ar-H), 6.01
3
3
(
d, J ¼ 5.4 Hz, 1H, 1-H), 5.47 (dd, J ¼ 3.4, 1.4 Hz, 1H, 4-H), 5.12 (dd,
J ¼ 10.9, 3.3 Hz, 1H, 3-H), 4.67 (ddd, J ¼ 7.1, 5.8, 1.3 Hz, 1H, 5-H), 4.26
(
(
dd, J ¼ 10.9, 5.4 Hz, 1H, 2-H), 4.08 (dd, J ¼ 11.5, 5.9 Hz, 1H, 6-CH ), 4.02
2
dd, J ¼ 11.4, 7.1 Hz, 1H, 6-CH ), 2.15 (s, 3H, COCH ), 2.07 (s, 3H,
2
1
3
3
COCH ), 1.98 (s, 3H, COCH ); C NMR (100 MHz, CDCl ): d ¼ 170.4,
3
3
3
1
2
70.0, 169.7, 134.9, 129.3, 128.3, 127.7, 84.2, 71.3, 69.1, 67.3, 61.6, 58.8,
9.8, 20.74, 20.71.
Phenyl 2-azido-4,6-O-benzylidene-2-deoxy-1-seleno-a-D-galactopyra-
noside (10). Compound 8 (0.5 g, 1.06 mmol) was dissolved in MeOH
2.2 mL). NaOMe (29 mg, 0.54 mmol) was added and the solution was
(
stirred at room temperature for 1 h. The solution was neutralized with
þ
Amberlite IR 120 (H ) ion exchange resin. The filtrate was evaporated to
afford 9 (364 mg, 1.06 mmol, quant.). Compound 9 (364 mg, 1.06 mmol)
was then dissolved in 2.2 mL anhydrous DMF under argon, followed by the
addition of benzaldehyde dimethyl acetal (0.2 mL, 1.33 mmol) and p-TsOH
(
24 mg, 0.14 mmol) at room temperature. The reaction mixture was stirred
ꢂ
at 60 C for 7 h, DMF was removed under reduced pressure. The residue
was diluted with ethyl acetate (3 mL) and washed with satd. aq. NaHCO3
(
(
(
3 ꢄ 5 mL). The aqueous phase was extracted with ethyl acetate
2 ꢄ 10 mL), and the combined organic phase was washed with brine
30 mL) and dried over Na SO . The crude residue was purified by silica
2
4
gel column chromatography (petroleum ether: ethyl acetate 2: 1 v/v) to
1
yield 10 (400 mg, 0.93 mmol, 88%). H NMR (400 MHz, CDCl3)
d ¼ 7.70 ꢃ 6.95 (m, 10H, Ar-H), 6.04 (d, J ¼ 5.0 Hz, 1H, 1-H), 5.61 (s, 1H,
PhCH), 4.33 (dd, J ¼ 3.7, 1.3 Hz, 1H, 3-H), 4.19 (dd, J ¼ 7.0, 1.5 Hz, 1H, 6-
CH ), 4.17 (d, J ¼ 1.3 Hz, 1H, 5-H), 4.16 ꢃ 4.12 (m, 1H, 2-H), 4.10 (dd,
2
J ¼ 12.9, 2.1 Hz, 1H, 6-CH ), 3.94 (td, J ¼ 10.2, 3.7 Hz, 1H, 3-H), 2.55 (d,
2
1
3
J ¼ 10.2 Hz, 1H, 3-OH); C NMR (100 MHz, CDCl ): d ¼ 137.1, 133.8,
3

JOURNAL OF CARBOHYDRATE CHEMISTRY
9
1
6
29.5, 129.2, 128.4, 127.8, 126.2, 101.4, 85.2, 77.2, 75.0, 70.7, 69.1,
5.1, 62.1.
Phenyl 2-azido-3-O-acetyl-4,6-O-benzylidene-2-deoxy-1-seleno-a-D-gal-
actopyranoside (11). To a solution of compound 10 (400 mg, 0.93 mmol)
in pyridine (1.9 mL) under argon, Ac O (0.34 mL, 3.60 mmol) was added
2
ꢂ
dropwise at 0 C. After stirring for 4 h at room temperature, the volatiles
was evaporated under reduced pressure at 30 C. The residue was co-evapo-
rated with toluene to give product 11 (417 mg, 0.88 mmol, 95%). H NMR
ꢂ
1
(
1
400 MHz, CDCl ) d ¼ 7.88 ꢃ 7.21 (m, 10H, Ar-H), 6.09 (d, J ¼ 5.2 Hz, 1H,
3
-H), 5.55 (s, 1H, PhCH), 5.07 (dd, J ¼ 10.8, 3.4 Hz, 1H, 3-H), 4.52 (d,
J ¼ 2.7 Hz, 1H, 4-H), 4.50 (d, J ¼ 5.2 Hz, 1H, 2-H), 4.17 ꢃ 4.16 (m, 1H, 5-
H), 4.15 ꢃ 4.11 (m, 1H, 6-CH ), 4.06 (dd, J ¼ 12.7, 1.7 Hz, 1H, 6-CH ), 2.17
2
2
(
s, 3H, COCH ).
3
Phenyl
2-azido-3-O-acetyl-4-O-benzyl-2-deoxy-1-seleno-a-D-galacto-
pyranoside (12). Compound 11 (100 mg, 0.21 mmol) was co-evaporated
with toluene and dissolved under argon in anhydrous DCM (2 mL). A 1 M
solution of BH ꢁTHF (1.2 mL, 1.20 mmol) was added and the solution was
3
ꢂ
cooled to 0 C, TMSOTf (180 lL, 0.99 mmol) was added dropwise. The
reaction mixture was stirred at room temperature for 1 h. The solution was
diluted with DCM (3 mL) and extracted with satd. aq. NaHCO3
(
2 ꢄ 20 mL). The organic phase was dried over Na SO and the solvent was
2
4
removed under vacuum. The residue was purified by silica gel column
chromatography (petroleum ether: ethyl acetate 8: 1 v/v) to give 12 (80 mg,
1
0
.17 mmol, 81%). H NMR (400 MHz, CDCl ) d ¼ 7.89 ꢃ 7.07 (m, 10H, Ar-
3
H), 6.00 (d, J ¼ 5.4 Hz, 1H, 1-H), 5.07 (dd, J ¼ 10.8, 3.0 Hz, 1H, 3-H), 4.70
(
d, J ¼ 11.5 Hz, 1H, PhCH ), 4.52 (d, J ¼ 11.5 Hz, 1H, PhCH ), 4.45 (dd,
2
2
J ¼ 10.8, 5.4 Hz, 1H, 2-H), 4.28 (dd, J ¼ 6.9, 5.3 Hz, 1H, 5-H), 4.07 (dd,
J ¼ 3.0, 1.2 Hz, 1H, 4-H), 3.67 (dd, J ¼ 11.4, 7.1 Hz, 1H, 6-CH ), 3.49 (dd,
2
J ¼ 11.4, 5.0 Hz, 1H, 6-CH ), 2.12 (s, 3H, COCH ), 1.57 (s, 1H, 6-OH).
2
3
Phenyl 2-azido-3-O-acetyl-4-O-benzyl-2-deoxy-6-O-(p-toluenesulfonyl)-
-seleno-a-D-galactopyranoside (13). To a solution of 12 (68 mg,
.14 mmol) in anhydrous pyridine (1 mL), p-toluene-sulfonyl chloride
1
0
(
68 mg, 0.36 mmol) was added under argon. The reaction mixture was
stirred at room temperature for 12 h. The mixture was diluted with DCM
2 mL), washed with 1 M aq. HCl (2 ꢄ 3 mL), satd. aq. NaHCO (3 ꢄ 5 mL)
(
3
and water (2 ꢄ 5 mL). The combined organic phase was dried (Na SO )
2
4
and concentrated. The residue was purified by silica gel column chroma-
tography (petroleum ether: ethyl acetate 4: 1 v/v) to give product 13
1
(
1
48 mg, 0.08 mmol, 57%). H NMR (400 MHz, CDCl ) d ¼ 7.88 ꢃ 7.14 (m,
3
4H, Ar-H), 5.85 (d, J ¼ 5.3 Hz, 1H, 1-H), 4.98 (dd, J ¼ 10.8, 2.9 Hz, 1H, 3-
H), 4.63 (d, J ¼ 11.3 Hz, 1H, PhCH ), 4.48 (td, J ¼ 6.4, 1.3 Hz, 1H, 5-H),
2
4
.44 (d, J ¼ 11.3 Hz, 1H, PhCH ), 4.35 (dd, J ¼ 10.8, 5.4 Hz, 1H, 2-H), 4.03
2

1
0
C. QIN ET AL.
(
(
dd, J ¼ 3.0, 1.2 Hz, 1H, 4-H), 3.98 (dd, J ¼ 10.1, 6.3 Hz, 1H, 6-CH ), 3.90
13
2
dd, J ¼ 10.1, 6.5 Hz, 1H, 6-CH ), 2.42 (s, 3H, CH ), 2.10 (s, 3H, CH );
C
2
3
3
NMR (100 MHz, CDCl ) d ¼ 169.9, 145.1, 137.1, 135.1, 132.4, 129.9, 129.2,
3
1
2
28.6, 128.2, 128.04, 127.97, 127.4, 84.4, 75.3, 73.7, 73.4, 70.1, 67.1, 59.0,
1.7, 20.8.
Phenyl 2-azido-2-deoxy-6-O-(p-toluenesulfonyl)-1-seleno-a-D-galacto-
pyranoside (15). The trihydroxygalatose 9 (327 mg, 0.95 mmol) was dis-
solved in anhydrous pyridine (8 mL), then p-toluene-sulfonyl chloride
(
253 mg, 1.33 mmol) was added under nitrogen. The reaction mixture was
stirred at room temperature for 12 h. When the starting material was con-
sumed completely, the solution was diluted by DCM (10 mL) and treated
with 1 M aq. HCl (2 ꢄ 20 mL) and washed with satd. aq. NaHCO
3
(
3 ꢄ 20 mL) and water (2 ꢄ 20 mL). Combined the organic layer and dried
over Na SO . The residue was concentrated in vacuo and then purified by
2
4
column chromatography on silica gel (DCM: MeOH 200: 1, v/v) to yield
2
0
ꢂ
1
1
(
1
4
(
(
(
5 (384 mg, 0.77 mmol, 81%). [a]D ¼ 133.6 (c ¼ 1.00, CHCl ); H NMR
3
400 MHz, CDCl ) d ¼ 7.72 (d, J ¼ 8.3 Hz, 2H, Ar-H), 7.58 (dt, J ¼ 6.7,
3
.6 Hz, 2H, Ar-H), 7.36 ꢃ 7.23 (m, 5H, Ar-H), 5.86 (d, J ¼ 5.3 Hz, 1H, 1-H),
.57 ꢃ 4.50 (m, 1H, 5-H), 4.29 (dd, J ¼ 10.6, 6.0 Hz, 1H, 6-CH ), 4.10 ꢃ 3.93
2
m, 3H, 2-H, 4-H, 6-CH ), 3.78 (ddd, J ¼ 9.8, 6.0, 3.3 Hz, 1H, 3-H), 2.68
2
1
3
dd, J ¼ 6.5, 4.8 Hz, 2H, 3-OH, 4-OH), 2.44 (s, 3H, CH ); C NMR
3
100 MHz, CDCl ) d ¼ 145.2, 135.0, 132.4, 132.1, 132.0, 129.9, 129.2, 128.8,
3
1
28.7, 128.2, 128.0, 127.7, 84.6, 77.2, 70.6, 70.0, 67.9, 67.6, 61.6, 21.7.
Phenyl 2-azido-2-deoxy-1-seleno-a-D-fucopyranoside (16). Tosylate
compound 15 (380 mg, 0.76 mmol) was refluxed for 12 h in butanone
10 mL) together with NaI (568 mg, 3.79 mmol) under nitrogen. When the
(
TLC showed the starting material was complete, the reaction mixture was
cooled to room temperature and diluted with ethyl acetate (10 mL) and
then washed with 1 M aq. Na S O (2 ꢄ 30 mL) and water (2 ꢄ 30 mL).
2
2 3
Combine the organic layer, dried with Na SO , and concentrated in vacuo.
2
4
The residue was purified by column chromatography on silica gel (petrol-
eum ether: ethyl acetate 5: 1 v/v) to yield iodide compound 15a (259 mg,
2
0
ꢂ
1
0
.57 mmol, 75%). [a]D ¼ 317.6 (c ¼ 1.00, CHCl ); H NMR (400 MHz,
3
CDCl ) d ¼ 7.65 ꢃ 7.63 (m, 2H, Ar-H), 7.33 ꢃ 7.29 (m, 3H, Ar-H), 5.96 (d,
3
J ¼ 5.3 Hz, 1H, 1-H), 4.41 (m, 1H, 5-H), 4.28 (d, J ¼ 3.7 Hz, 1H, 4-H), 4.09
(
3
2
dd, J ¼ 10.2, 5.3 Hz, 1H, 2-H), 3.79 (ddd, J ¼ 9.9, 6.1, 3.3 Hz, 1H, 3-H),
.37 (dd, J ¼ 12.7, 8.2 Hz, 1H, 6-Ha), 3.20 (dd, J ¼ 12.7, 6.0 Hz, 1H, 6-Hb),
.55 (d, J ¼ 6.2 Hz, 1H, 3-OH), 2.35 (d, J ¼ 3.9 Hz, 1H, 4-OH).
Then to a solution of the iodide compound 15a (259 mg, 0.57 mmol) in
anhydrous DMF (15 mL), sodium cyanoborohydride (182 mg, 2.90 mmol)
ꢂ
was added. The reaction mixture was heated to 95 C and stirred for 12 h.
When the TLC showed the starting material consumed completely, the

JOURNAL OF CARBOHYDRATE CHEMISTRY
11
reaction mixture was cooled to room temperature and then quenched with
water (2 mL), extracted with ethyl acetate (2 ꢄ 10 mL). Separated organic
phase and washed with water (3 ꢄ 30 mL). The organic layer was dried
over Na SO , filtered, and concentrated in vacuo. The residue was purified
2
4
by silica gel column chromatography (petroleum ether: ethyl acetate 1: 1 v/
2
0
ꢂ
v) to afford 16 (133 mg, 0.41 mmol, 72%). [a]D ¼259.4 (c ¼ 1.00,
1
CHCl3); H NMR (400 MHz, CDCl ) d ¼ 7.73 ꢃ 7.45 (m, 2H, Ar-H),
3
7
6
3
1
1
.40 ꢃ 6.93 (m, 3H, Ar-H), 5.92 (d, J ¼ 5.3 Hz, 1H, 1-H), 4.39 (dt, J ¼ 7.4,
.0 Hz, 1H, 5-H), 4.05 (dd, J ¼ 10.0, 5.3 Hz, 1H, 2-H), 3.91 ꢃ 3.74 (m, 2H,
-H, 4-H), 2.60 (d, J ¼ 6.3 Hz, 1H, 3-OH), 2.26 (d, J ¼ 4.0 Hz, 1H, 4-OH),
1
3
.27 (d, J ¼ 6.6 Hz, 3H, 6-CH ); C NMR (100 MHz, CDCl ) d ¼ 134.5,
3
3
29.2, 127.9, 85.0, 77.2, 71.5, 71.3, 68.7, 61.9, 16.0; HR-ESI-MS m/z:
þ
þ
[
M þ Na] Calcd for C H N O SeNa 346.0230; Found 346.0226.
1
2
15 3 3
Phenyl 2-azido-3-O-methoxybenzyl-2-deoxy-1-seleno-a-D-fucopyrano-
side (17). Compound 16 (3 g, 9.14 mmol) was dissolved in anhydrous tolu-
ene (54 mL) and dibutyltin oxide (3.5 g, 14.06 mmol) was added under
ꢂ
argon. The reaction mixture was heated to 118 C and refluxed for 2 h.
ꢂ
Then the solution was cooled to 60 C, 4-methoxybenzylchloride (1.9 mL,
14.01 mmol) and tetrabutylammonium iodide (5.1 g, 13.81 mmol) was
added and refluxed for 2 h. The solution was cooled to room temperature,
diluted with ethyl acetate (80 mL), and washed with water (2 ꢄ 100 mL).
The organic phase was dried over Na SO and concentrated under reduced
2
4
pressure. The residue was purified by column chromatography on silica gel
(
6
petroleum ether: ethyl acetate 6: 1 v/v) to afford the compound 17 (2.7 g,
2
0
ꢂ
1
.02 mmol, 66%). [a]D ¼ 137.9 (c ¼ 1.00, CHCl ); H NMR (400 MHz,
3
CDCl ) d ¼ 7.60 ꢃ 7.52 (m, 2H, Ar-H), 7.33 (d, J ¼ 8.6 Hz, 2H, Ar-H), 7.28
3
(
dd, J ¼ 5.0, 2.0 Hz, 3H, Ar-H), 6.92 (d, J ¼ 8.6 Hz, 2H, Ar-H), 5.88 (d,
J ¼ 5.4 Hz, 1H, 1-H), 4.70 (d, J ¼ 11.0 Hz, 1H, PhCH ), 4.63 (d, J ¼ 11.0 Hz,
2
1
3
3
H, PhCH ), 4.36 ꢃ 4.24 (m, 1H, 5-H), 4.15 (dd, J ¼ 10.2, 5.3 Hz, 1H, 2-H),
2
.86 (dt, J ¼ 3.2, 1.5 Hz, 1H, 4-H), 3.82 (s, 3H, CH ), 3.69 (dd, J ¼ 10.2,
3
.2 Hz, 1H, 3-H), 2.35 (t, J ¼ 1.6 Hz, 1H, 4-OH), 1.26 (d, J ¼ 6.6 Hz, 3H, 6-
13
CH ); C NMR (100 MHz, CDCl ) d ¼ 159.7, 134.4, 129.8, 129.10, 129.08,
3
3
1
27.8, 114.1, 85.3, 78.9, 71.8, 68.61, 68.55, 60.2, 55.3, 16.1; HR-ESI-MS m/z:
þ
þ
[
M þ Na] Calcd for C H N O SeNa 472.0751; Found 472.0725.
2
0
23 3 4
Phenyl 2-azido-4-O-benzyl-3-O-methoxybenzyl-2-deoxy-1-seleno-a-D-
fucopyranoside (18). Compound 17 (2.2 g, 4.91 mmol) was dissolved in
ꢂ
anhydrous DMF (30 mL) and cooled to 0 C for 30 min. Sodium hydride
(
235 mg, 9.79 mmol) was added and kept in ice bath for 30 min. Benzyl
bromide (1.2 mL, 10.10 mmol) was added dropwise and the solution was
allowed to warm to room temperature for 2 h. After the complete conver-
sion of the starting material, the reaction mixture was diluted with DCM
(
80 mL) and then quenched with water (50 mL). Extracted with DCM

1
2
C. QIN ET AL.
(
3 ꢄ 100 mL) and brine (100 mL), the organic phase was separated, dried
over Na SO and concentrated in vacuo. The residue was purified with col-
2
4
umn chromatography on silica gel (petroleum ether: ethyl acetate 20: 1 v/v)
2
0
ꢂ
1
to yield 18 (1.9 g, 3.53 mmol, 72%). [a]D ¼ 71.5 (c ¼ 1.00, CHCl ); H
3
NMR (400 MHz, CDCl ) d ¼ 7.57 ꢃ 7.55 (m, 2H, Ar-H), 7.36 ꢃ 7.25 (m,
3
1
0H, Ar-H), 6.94 ꢃ 6.91 (m, 2H, Ar-H), 5.92 (d, J ¼ 5.3 Hz, 1H, 1-H), 4.94
(
d, J ¼ 11.4 Hz, 1H, PhCH ), 4.77 ꢃ 4.66 (m, 2H, PhCH ), 4.60 (d,
2
2
J ¼ 11.5 Hz, 1H, PhCH ), 4.33 (dd, J ¼ 10.2, 5.3 Hz, 1H, 2-H), 4.21 (q,
2
J ¼ 6.5 Hz, 1H, 5-H), 3.83 (s, 3H, OCH ), 3.71 (dd, J ¼ 10.3, 2.7 Hz, 1H, 3-
3
1
3
H), 3.68 (dd, J ¼ 2.8, 1.1 Hz, 1H, 4-H), 1.12 (d, J ¼ 6.4 Hz, 3H, 6-CH );
C
3
NMR (100 MHz, CDCl ) d ¼ 159.6, 138.3, 134.5, 129.7, 129.2, 128.9, 128.4,
3
1
1
28.3, 127.9, 127.8, 114.1, 85.8, 80.5, 77.2, 76.0, 75.1, 72.4, 69.6, 61.0, 55.5,
þ
þ
6.7; HR-ESI-MS m/z: [M þ Na] Calcd for C H N O SeNa 562.1221;
2
7
29 3 4
Found 562.1209.
Phenyl 2-azido-3-O-acetyl-4-O-benzyl-2-deoxy-1-seleno-a-D-fucopyra-
noside (19). To a solution of compound 18 (900 mg, 1.67 mmol) in DCM
(
(
84 mL) and water (5 mL), 2,3-dicyano-5,6-dichlorobenzoquinone (DDQ)
564 mg, 2.48 mmol) was added. The reaction mixture was stirred at room
temperature for 7 h. After that, the solution was diluted with DCM
100 mL), washed with 10% (w/v) Na S O . Combined all organic layer,
(
2
2 3
dried over Na SO and concentrated under vacuum. The residue was puri-
2
4
fied by column chromatography on silica gel (petroleum ether: ethyl acetate
0: 1 v/v) to afford 3-OH compound 18a (573 mg, 1.37 mmol, 82%). Then
1
the 3-OH compound 18a (535 mg, 1.28 mmol) was dissolved in pyridine
ꢂ
(
3 mL) at 0 C followed by addition of acetic anhydride (0.5 mL,
5.29 mmol). After stirring at room temperature for 5 h, the solution was
washed with 1 M aq. HCl, and then extracted with ethyl acetate, satd. aq.
NaHCO . The organic layer was dried over Na SO , concentrated under
3
2
4
vacuum. The residue was purified by column chromatography (petroleum
1
ether: ethyl acetate 20: 1 v/v) to afford 19 (587 mg, 1.28 mmol, quant.). H
NMR (400 MHz, CDCl ) d ¼ 7.68 ꢃ 7.21 (m, 10H, Ar-H), 5.91 (d,
3
J ¼ 5.3 Hz, 1H, 1-H), 5.46 (dd, J ¼ 3.3, 1.2 Hz, 1H, 4-H), 4.75 (d,
J ¼ 10.7 Hz, 1H, PhCH ), 4.53 (d, J ¼ 10.7 Hz, 1H, PhCH ), 4.48 ꢃ 4.37 (m,
2
2
1
1
H, 5-H), 4.12 (dd, J ¼ 10.3, 5.4 Hz, 1H, 2-H), 3.78 (dd, J ¼ 10.4, 3.3 Hz,
13
H, 3-H), 2.15 (s, 3H, COCH ), 1.12 (d, J ¼ 6.5 Hz, 3H, 6-CH ); C NMR
3
3
(
8
100 MHz, CDCl ) d ¼ 170.5, 136.9, 134.5, 129.1, 128.5, 128.3, 128.1, 127.9,
3
þ
5.1, 71.7, 68.9, 67.8, 60.4, 20.8, 16.1; HR-ESI-MS m/z: [M þ Na] Calcd
þ
for C H N O SeNa 484.0751; Found 484.0749.
21
23 3 4
N-Benzyl-N-benzyloxycarbonyl-3-aminopropyl 2-azido-3-O-acetyl-4-O-
benzyl-2-deoxy-b-D-fucopyranoside (21). To a mixture of compound 19
ꢂ
(
580 mg, 1.26 mmol) in tetrahydrofuran (6 mL) and water (6 mL) at 0 C,
N-bromosuccinimide (538 mg, 3.02 mmol) was added. The stirring was

JOURNAL OF CARBOHYDRATE CHEMISTRY
13
continued for 2 h at room temperature and TLC showed the starting mater-
ial consumed. The mixture was diluted with DCM (15 mL), washed with
1
0% (w/v) Na S O , satd. aq. NaHCO . Organic layer was separated, dried
2 2 3 3
over Na SO and concentrated. The residue was purified by column chro-
2
4
matography (petroleum ether: ethyl acetate 4: 1 v/v) to give hemiacetal 19a
2
0
ꢂ
1
(
(
1
404 mg, 1.26 mmol, quant.). [a]D ¼ 54.9 (c ¼ 1.00, CHCl ); H NMR
3
400 MHz, CDCl ) d ¼ 7.43 ꢃ 7.30 (m, 8H, Ar-H), 5.47 (dd, J ¼ 3.3, 1.3 Hz,
3
H, 1a-H), 5.34 (dd, J ¼ 3.4, 1.1 Hz, 0.8H, 4 b-H), 5.32 (d, J ¼ 3.6 Hz, 1H,
4
a-H), 4.77 (d, J ¼ 10.8 Hz, 1H, PhCH ), 4.75 (d, J ¼ 11.1 Hz, 0.8H,
2
PhCH ), 4.54 (d, J ¼ 7.9 Hz, 1H, 1 b-H), 4.53 (d, J ¼ 10.8 Hz, 1H, PhCH ),
2
2
4
(
(
3
.53 (d, J ¼ 11.1 Hz, 0.8H, PhCH ), 4.32 (qd, J ¼ 6.6, 1.3 Hz, 1H, 5-H) , 4.03
2
dd, J ¼ 10.5, 3.2 Hz, 1H, 2a-H), 3.74 (dd, J ¼ 10.5, 3.5 Hz, 1H, 3a-H), 3.69
td, J ¼ 6.4, 1.1 Hz, 0.8H, 5 b-H), 3.58 (dd, J ¼ 10.2, 7.9 Hz, 0.8H, 2 b-H),
.45 (dd, J ¼ 10.3, 3.4 Hz, 0.8H, 3 b-H), 2.19 (s, 2.4H, COCH ), 2.18 (s, 3H,
3
COCH ), 1.25 (d, J ¼ 6.5 Hz, 2.4H, 6 b-CH ), 1.19 (d, J ¼ 6.5 Hz, 3H, 6a-
3
3
13
CH ); C NMR (100 MHz, CDCl ) d ¼ 170.90, 170.88, 137.2, 137.0, 128.6,
3
3
1
7
28.5, 128.4, 128.22, 128.17, 96.2, 92.5, 77.9, 77.5, 77.4, 77.2, 76.8, 74.4,
1.9, 71.7, 69.7, 69.5, 68.4, 65.2, 64.0, 59.8, 21.0, 20.9, 16.6, 16.4; HR-ESI-
þ
þ
MS m/z: [M þ Na] Calcd for C H N O Na 344.1217; Found 344.1208.
1
5
19 3 5
To a solution of the hemiacetal 19a (404 mg, 1.26 mmol) in anhydrous
ꢂ
DCM (14 mL) at 0 C was added trichloroacetonitrile (0.4 mL, 3.99 mmol)
and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) (23 lL, 0.15 mmol). The stir-
ꢂ
ring was continued for 5 h and concentrated under 30 C. The residue was
purified by column chromatography (petroleum ether: ethyl acetate 10: 1 v/
v) to give imidate 20 (520 mg, 1.12 mmol, 89%).
Trichloroacedimidate donor 20 (520 mg, 1.12 mmol), N-Bn-N-Cbz-3-ami-
[
46]
nopropan-1-ol
(700 mg, 2.34 mmol) were dissolved in anhydrous DCM
(
130 mL). This solution was treated with freshly activated 4 Å MS and was
stirred for 30 min at room temperature. This solution was then cooled to
ꢂ
ꢃ40 C and TMSOTf (0.3 mL, 1.66 mmol) was slowly added. The mixture
ꢂ
stirring was continued for 4 h at ꢃ40 C and TLC showed the reaction
complete. The mixture was quenched with Et N (1 mL) and filtered. The
3
filtrate was evaporated and the residue was purified by column chromatog-
raphy (petroleum ether: ethyl acetate 6: 1 v/v) to give coupled product
(
(
(
572 mg, 0.95 mmol, 85%, a/b ¼ 1: 1) including target b-product 21
20 1
ꢂ
286 mg, 0.47 mmol). [a]D
¼ ꢃ10.8 (c ¼ 1.00, CHCl ); H NMR
3
400 MHz, CDCl ) d ¼ 7.45–7.10 (m, 15H, 3Ph), 5.17 (d, J ¼ 9.3 Hz, 2H,
3
PhCH ), 4.74–4.59 (m, 3H, 3-H, PhCH ), 4.57–4.44 (m, 2H, NPhCH ),
2
2
2
4
.21 (d, J ¼ 8.0 Hz, 1H, 1-H), 4.02–3.83 (m, 1H, linker-OCH), 3.75 (t,
J ¼ 9.5 Hz, 1H, 2-H), 3.64 (d, J ¼ 3.0 Hz, 1H, 4-H), 3.59–3.27 (m, 4H, 5-H,
linker-OCH, linker-NCH ), 2.04 (s, 3H, COCH ), 1.98–1.76 (m, 2H, linker-
2
3
1
3
CH ), 1.21 (d, J ¼ 6.4 Hz, 3H, 6-CH ); C NMR (100 MHz, CDCl3)
2
3

1
4
C. QIN ET AL.
d ¼ 170.4, 138.0, 137.7, 128.52, 128.46, 128.4, 128.3, 128.0, 127.92, 127.87,
1
2
27.3, 102.0, 77.3, 76.2, 75.6, 74.2, 70.5, 67.4, 67.2, 61.1, 50.9, 44.7, 43.6,
þ
8.5, 28.0, 20.9, 16.6; HR-ESI-MS m/z: [M þ Na]
Calcd for
þ
C H N O Na 625.2633; Found 625.2650.
33
38 4 7
N-Benzyl-N-benzyloxycarbonyl-3-aminopropyl 2-azido-4-O-benyzl-2-
deoxy-b-D-fucopyranoside (4). To a solution of compound 21 (262 mg,
0.43 mmol) in MeOH (4 mL), NaOMe (40 mg, 0.74 mmol) was added. The
solution was stirred at room temperature for 2 h. The reaction mixture was
þ
diluted with methanol and neutralized with Amberlite IR 120 H resin.
After filtration, the filtrate was concentrated in reduced pressure and puri-
fied by column chromatography (petroleum ether: ethyl acetate 3:1 v/v) to
2
0
ꢂ
afford 4 (243 mg, 0.43 mmol, quant.). [a]D ¼ ꢃ24.1 (c ¼ 1.00, CHCl );
3
1
H NMR (400 MHz, CDCl ) d ¼ 7.76 ꢃ 7.10 (m, 15H, Ar-H), 5.22 (d,
3
J ¼ 9.4 Hz, 2H, PhCH ), 4.83 (d, J ¼ 11.6 Hz, 1H, PhCH ), 4.78 (d,
2
2
J ¼ 11.6 Hz, 1H, PhCH ), 4.58 (d, J ¼ 14.0 Hz, 2H, PhCH ), 4.25 ꢃ 4.08 (m,
2
2
1
4
2
H, 1-H), 4.05 ꢃ 3.86 (m, 1H, linker-OCH ), 3.62 ꢃ 3.34 (m, 7H, 2-H, 3-H,
2
-H, 5-H, linker-OCH, linker-NCH ), 2.46 (s, 1H, 3-OH), 1.96 ꢃ 1.76 (m,
2
1
3
H, linker-CH ), 1.30 (d, J ¼ 6.4 Hz, 3H, 6-CH ); C NMR (100 MHz,
2
3
CDCl ) d ¼ 138.0, 128.58, 128.56, 128.5, 128.3, 128.1, 128.0, 127.9, 102.1 (1-
3
C), 78.5, 77.4, 75.9, 73.0, 70.8, 67.2, 64.7, 50.9, 44.8, 43.7, 28.6, 28.1, 16.9;
þ
þ
HR-ESI-MS m/z: [M þ Na]
Calcd for C H N O Na
583.2527;
3
1
36 4 6
Found 583.2531.
Allyl 2-azido-2-deoxy-b-L-fucopyranoside (23). Ceric ammonium
nitrate (8.2 g, 14.96 mmol) and sodium azide (0.73 g, 11.23 mmol) were
[
46]
added to a solution of L-fucal 22
(1.0 g, 4.67 mmol) in anhydrous aceto-
ꢂ
nitrile (25 mL) at ꢃ15 C under argon, and the resulting mixture was
ꢂ
stirred for 3 h at ꢃ15 C. After that, the volatiles were evaporated under
ꢂ
reduced pressure at 28 C. The residue was dissolved in a mixture of
diethyl ether and ethyl acetate (1: 1 v/v, 50 mL) and washed with water
(
10 mL). The organic phase was separated and the aqueous layer was
extracted with a mixture of diethyl ether and ethyl acetate (1: 1 v/v)
(
2 ꢄ 25 mL). The combined organic phase was dried with Na SO and con-
2
4
centrated, and the residue was dried in vacuo for 4 h.
The crude residue was dissolved in allyl alcohol (5.0 mL, 73.17 mmol)
ꢂ
under argon, cooled to 0 C, sodium (100 mg, 4.35 mmol) was added por-
ꢂ
tionwise, and the resulting mixture was stirred for 2 h at 0 C. After that,
the reaction mixture was diluted with MeOH (20 mL), neutralized with
þ
Amberlite IR 120 (H ) ion exchange resin. The combined filtrate was dried
with Na SO and concentrated in vacuo. The residue was purified by col-
2
4
umn chromatography on silica gel (petroleum ether: ethyl acetate) to yield
2
0
ꢂ
product 23 (713 mg, 3.11 mmol, 67%). [a]D ¼ ꢃ27.6 (c ¼ 1.00, CHCl );
3
IR mmax (film) 3312, 2865, 2111, 1348, 1279, 1162, 1071, 999, 925, 755

JOURNAL OF CARBOHYDRATE CHEMISTRY
15
ꢃ1
1
cm ; H NMR (400 MHz, CDCl ) d ¼ 6.04–5.85 (m, 1H, CH¼C), 5.34
3
(
dq, J ¼ 17.3, 1.6 Hz, 1H, C¼CHa), 5.23 (dd, J ¼ 10.5, 1.6 Hz, 1H,
C ¼ CHb), 4.41 (ddt, J ¼ 12.9, 5.3, 1.5 Hz, 1H, OCHa), 4.30 (d, J ¼ 7.9 Hz,
1
1
(
H, 1-H), 4.14 (ddt, J ¼ 12.8, 6.1, 1.4 Hz, 1H, OCHb), 3.70 (d, J ¼ 3.2 Hz,
H, 4-H), 3.63–3.53 (m, 1H, 5-H), 3.53 (dd, J ¼ 10.1, 7.8 Hz, 1H, 2-H), 3.45
dd, J ¼ 10.1, 3.3 Hz, 1H, 3-H), 3.04 (s, 1H, OH), 2.68 (s, 1H, OH), 1.35 (d,
13
J ¼ 6.5 Hz, 3H, 6-CH ); C NMR (100 MHz, CDCl ) d ¼ 133.5, 117.8,
3
3
þ
1
01.1, 72.6, 70.9, 70.6, 70.3, 64.0, 16.3; HR-ESI-MS m/z: [M þ Na] Calcd
þ
for C H N O Na 252.0960; Found 252.0954.
9
15 3 4
Allyl 2-azido-2-deoxy-3-O-(2-naphthyl)methyl-b-L-fucopyranoside (24).
To a mixture of compound 23 (450 mg, 1.96 mmol) in toluene (22 mL),
dibutyltin oxide (814 mg, 3.27 mmol) was added. The reaction mixture was
ꢂ
heated to 110 C and continued for 1 h. Then the solution was cooled to
ꢂ
4
0 C, 2-(bromomethyl)naphthalene (723 mg, 3.27 mmol) and tetrabu-
ꢂ
tylammonium bromide (1.05 g, 3.26 mmol) was added. The stirring at 70 C
was continued for 12 h. After that, the solution was diluted with ethyl acet-
ate (30 mL), washed with brine and evaporated. The residue was purified
by column chromatography (petroleum ether: ethyl acetate 5: 1 v/v) to
2
0
ꢂ
1
afford 24 (628 mg, 1.70 mmol, 87%). [a]D ¼ 34.0 (c ¼ 1.00, CHCl ); H
3
NMR (400 MHz, CDCl ) d ¼ 7.85 (dt, J ¼ 10.5, 7.7 Hz, 4H, Ar-H),
3
7
5
.59 ꢃ 7.45 (m, 3H, Ar-H), 5.94 (ddt, J ¼ 16.8, 10.9, 5.6 Hz, 1H, Ally-CH),
.33 (dd, J ¼ 17.2, 1.7 Hz, 1H, Ally-CH ), 5.21 (dd, J ¼ 10.5, 1.5 Hz, 1H,
2
Ally-CH ), 4.88 (s, 2H, NapCH ), 4.42 (dd, J ¼ 12.9, 6.2 Hz, 1H, Ally-
2
2
OCH ), 4.23 (d, J ¼ 8.1 Hz, 1H, 1-H), 4.12 (dd, J ¼ 12.9, 6.2 Hz, 1H, Ally-
2
OCH ), 3.74 (d, J ¼ 3.3 Hz, 1H, 4-H), 3.66 (dd, J ¼ 10.0, 8.0 Hz, 1H, 2-H),
2
3
.47 (q, J ¼ 6.5 Hz, 1H, 5-H), 3.35 (dd, J ¼ 10.0, 3.3 Hz, 1H, 3-H), 2.32 (s,
13
1
H, 4-OH), 1.34 (d, J ¼ 6.4 Hz, 3H, 6-CH ); C NMR (100 MHz, CDCl )
3
3
d ¼ 134.7, 133.7, 133.2, 128.6, 127.9, 127.8, 127.0, 126.3, 126.2, 125.8, 117.6,
00.8, 79.4, 77.2, 72.2, 70.2, 70.0, 68.3, 62.6, 16.3; HR-ESI-MS m/z:
1
[
þ
þ
M þ Na] Calcd for C H N O Na 391.1581; Found 391.1564.
2
0
23 3 4
Allyl 2-azido-4-O-benzyl-3-O-(2-naphthyl)methyl-2-deoxy-b-L-fucopyr-
anoside (25). Compound 24 (527 mg, 1.43 mmol) was dissolved in anhyd-
ꢂ
rous DMF (17 mL) and cooled to 0 C for 30 min. Sodium hydride (140 mg,
ꢂ
5
.83 mmol) was added and was continued for 30 min at 0 C. Then, benzyl
bromide (0.5 mL, 4.21 mmol) was added. The reaction mixture was stirred
for 5 h and diluted with DCM (20 mL), quenched with iced water, extracted
with satd. aq. NaHCO . Separated organic phase, dried over Na SO , and
3
2
4
concentrated in vacuo. The residue was purified by column chromatog-
raphy (petroleum ether: ethyl acetate 25: 1 v/v) to afford 25 (531 mg,
2
0
ꢂ
1
1
.16 mmol, 81%). [a]D ¼ 50.3 (c ¼ 1.00, CHCl ); H NMR (400 MHz,
3
CDCl ) d ¼ 7.90 ꢃ 7.77 (m, 4H, Ar-H), 7.57 ꢃ 7.45 (m, 3H, Ar-H),
3
7
.38 ꢃ 7.21 (m, 5H, Ar-H), 5.94 (dddd, J ¼ 16.9, 10.8, 6.1, 5.0 Hz, 1H,

1
6
C. QIN ET AL.
Ally-CH), 5.32 (dt, J ¼ 17.2, 1.7 Hz, 1H, Ally-CH ), 5.19 (dq, J ¼ 10.5,
2
1
.5 Hz, 1H, Ally-CH ), 4.97 (d, J ¼ 11.7 Hz, 1H, PhCH ), 4.87 (s, 2H,
2
2
NapCH ) 4.71 (d, J ¼ 11.7 Hz, 1H, PhCH ), 4.39 (ddt, J ¼ 12.9, 5.0, 1.6 Hz,
2
2
1
1
H, Ally-OCH ), 4.22 (d, J ¼ 8.0 Hz, 1H, 1-H), 4.10 (ddt, J ¼ 12.9, 6.1,
2
.4 Hz, 1H, Ally-OCH ), 3.87 (dd, J ¼ 10.4, 8.0 Hz, 1H, 2-H), 3.55 (d,
2
J ¼ 2.8 Hz, 1H, 4-H), 3.42 ꢃ 3.38 (m, 1H, 5-H), 3.36 (dd, J ¼ 10.4, 2.8 Hz,
1
3
1
H, 3-H), 1.20 (d, J ¼ 6.4 Hz, 3H, 6-CH ). C NMR (100 MHz, CDCl )
3
3
d ¼ 138.4, 135.3, 133.9, 133.4, 133.2, 128.6, 128.5, 128.4, 128.1, 127.9, 127.8,
1
6
4
26.8, 126.4, 126.2, 125.9, 117.6, 101.1, 81.1, 75.2, 74.9, 72.9, 70.7, 70.1,
þ
þ
3.3, 17.0; HR-ESI-MS m/z: [M þ Na] Calcd for C H N O Na
2
7
29 3 4
82.2050; Found 482.2041.
Allyl 2-azido-4-O-benzyl-2-deoxy-b-L-fucopyranoside (6). To a stirring
mixture of compound 25 (531 mg, 1.16 mmol) in DCM (50 mL) and water
ꢂ
(
5 mL) at 0 C, DDQ (540 mg, 2.38 mmol) was added. After stirring at
room temperature for 3 h, the mixture was washed by 10% (w/v) Na S O
2 3
2
and concentrated in vacuo. The residue was purified by column chromatog-
raphy (petroleum ether: ethyl acetate 6: 1 v/v) to afford 6 (345 mg,
2
0
ꢂ
1
1
.08 mmol, 93%). [a]D ¼ ꢃ3.6 (c ¼ 1.00, CHCl ); H NMR (400 MHz,
3
CDCl ) d ¼ 7.42 ꢃ 7.28 (m, 5H, Ar-H), 5.94 (dddd, J ¼ 16.7, 10.4, 6.1,
3
5
.1 Hz, 1H, Ally-CH), 5.33 (dq, J ¼ 17.2, 1.6 Hz, 1H, Ally-CH ), 5.21 (dq,
2
J ¼ 10.5, 1.4 Hz, 1H, Ally-CH ), 4.81 (d, J ¼ 11.6 Hz, 1H, PhCH ), 4.72 (d,
2
2
J ¼ 11.6 Hz, 1H, PhCH ), 4.41 (ddt, J ¼ 12.9, 5.1, 1.6 Hz, 1H, Ally-CH ),
2
2
4
3
2
.26 (d, J ¼ 7.7 Hz, 1H, 1-H), 4.11 (ddt, J ¼ 12.9, 6.1, 1.4 Hz, 1H, Ally-CH ),
2
.58 ꢃ 3.49 (m, 3H, 2-H, 4-H, 5-H), 3.45 (dd, J ¼ 10.4, 3.3 Hz, 1H, 3-H),
1
3
.14 (s, 1H, 3-OH), 1.31 (d, J ¼ 6.5 Hz, 3H, 6-CH ); C NMR (100 MHz,
3
CDCl ) d ¼ 138.0, 133.8, 128.7, 128.3, 128.2, 117.6, 101.1, 78.6, 76.0, 73.1,
3
þ
7
1.0, 70.2, 64.7, 17.0; HR-ESI-MS m/z: [M þ Na]
Calcd for
þ
C H N O Na 342.1424; Found 342.1430.
16
21 3 4
Ally 2-azido-4-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-glucopyrano-
syl)-2-deoxy-b-L-fucopyranoside (26). To a stirring mixture of glucosyl
[
49]
donor 5
(500 mg, 1.01 mmol), fucosyl acceptor 6 (165 mg, 0.52 mmol)
and fresh activated 4 Å MS in anhydrous DCM (10 mL) under argon. This
ꢂ
solution was stirred at room temperature for 30 min and cooled to 0 C
and TMSOTf (36 lL, 0.20 mmol) was added. The temperature was allowed
to warm at room temperature and the stirring continued for 5 h. After that,
the mixture was quenched with Et N and filtrated. The filtrate was concen-
3
trated in vacuo to give a residue that was purified by silica gel column
chromatography (petroleum ether: ethyl acetate 2: 1 v/v) to give 26
2
0
ꢂ
1
(
300 mg, 0.46 mmol, 88%, b-only). [a]D ¼ 2.3 (c ¼ 1.00, CHCl ); H
3
NMR (400 MHz, CDCl ) d ¼ 7.29 ꢃ 7.20 (m, 5H, Ar-H), 5.84 (ddt, J ¼ 16.4,
3
1
(
0.8, 5.6 Hz, 1H, Ally-CH), 5.23 (d, J ¼ 17.3 Hz, 1H, Ally-CH ), 5.17 ꢃ 5.05
2
0
0
0
m, 3H, Ally-CH , 3 -H, 4 -H), 5.03 (t, J ¼ 8.2 Hz, 1H, 2 -H), 4.80 (d,
2

JOURNAL OF CARBOHYDRATE CHEMISTRY
17
0
J ¼ 11.3 Hz, 1H, Bn-H), 4.77 (d, J ¼ 7.7 Hz, 1H, 1 -H), 4.46 (d, J ¼ 11.4 Hz,
1
4
6
H, Bn-H), 4.29 (dd, J ¼ 13.0, 5.0 Hz, 1H, Ally-CH ), 4.20 (dd, J ¼ 12.3,
2
0
0
.4 Hz, 1H, 6 -Ha), 4.17 ꢃ 4.08 (m, 2H, 6 -Hb, 1-H), 4.00 (dd, J ¼ 13.0,
0
.2 Hz, 1H, Ally-CH ), 3.66 (qd, J ¼ 10.3, 4.9 Hz, 3H, 5 -H, 2-H, 3-H), 3.43
2
(
d, J ¼ 2.5 Hz, 1H, 4-H), 3.35 (d, J ¼ 6.4 Hz, 1H, 5-H), 1.99 (s, 3H,
CH CO), 1.95 (s, 3H, CH CO), 1.92 (s, 3H, CH CO), 1.79 (s, 3H,
3
3
3
1
3
CH CO), 1.10 (d, J ¼ 6.3 Hz, 3H, 6-CH ); C NMR (100 MHz, CDCl3)
3
3
d ¼ 170.4, 170.1, 169.0, 168.9, 137.8, 133.5, 128.0, 127.9, 127.5, 117.2, 100.5,
9
2
6
8.5, 79.4, 77.0, 75.4, 74.7, 73.0, 71.9, 71.3, 70.1, 69.8, 68.0, 61.9, 61.6, 20.5,
þ
þ
0.3, 16.5; HR-ESI-MS m/z: [M þ Na] Calcd for C H N O Na
3
0
39 3 13
72.2375; Found 672.2377.
2-Azido-4-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-2-
deoxy-L-fucopyranose (27). Compound 26 (300 mg, 0.46 mmol) was dis-
ꢂ
solved in dry MeOH (23 mL) and heated to 40 C. Palladium chloride
(
16 mg, 0.09 mmol) was added and continued for 1 h. The mixture was fil-
trated and the filtration was extracted with DCM and satd. aq. NaHCO3.
Separated organic layer and concentrated in vacuo to give a residue that
was purified by column chromatography (petroleum ether: ethyl acetate 1:
2
0
ꢂ
1
v/v) to afford 27 (246 mg, 0.40 mmol, 87%). [a]D ¼ ꢃ7.1 (c ¼ 1.00,
1
CHCl ); H NMR (400 MHz, CDCl ) a-anomer d ¼ 7.35 ꢃ 7.22 (m, 5H, Ar-
3
3
0
0
0
H), 5.23 (d, J ¼ 3.5 Hz, 1H, 1-H), 5.22 ꢃ 5.00 (m, 3H, 2 -H, 3 -H, 4 -H),
0
4
(
(
3
1
.86 ꢃ 4.72 (m, 2H, 1 -H, PhCH ), 4.43 (d, J ¼ 11.0 Hz, 1H, PhCH ), 4.38
2
2
0
d, J ¼ 7.8 Hz, 1H, 1 -H), 4.28 (dd, J ¼ 10.6, 2.7 Hz, 1H, 3-H), 4.25 ꢃ 4.11
0
0
m, 2H, 6 –CH ), 4.11 ꢃ 4.02 (m, 1H, 5-H), 3.75 ꢃ 3.65 (m, 2H, 2-H, 5 -H),
2
.61 (d, J ¼ 2.8 Hz, 1H, 4-H), 2.01 (s, 3H, COCH ), 1.97 (s, 3H, COCH ),
3
3
.93 (s, 3H, COCH ), 1.72 (s, 3H, COCH ), 1.10 (d, J ¼ 6.4 Hz, 3H, 6-
3
3
0
CH ); b-anomer d ¼ 7.35 ꢃ 7.22 (m, 5H, Ar-H), 5.22 ꢃ 5.00 (m, 3H, 2 -H,
3
0
0
3
-H, 4 -H), 4.80 (d, J ¼ 11.5 Hz, 1H, PhCH ), 4.47 (d, J ¼ 11.3 Hz, 1H,
2
0
0
0
PhCH ), 4.38 (d, J ¼ 7.8 Hz, 1H, 1 -H), 4.22 ꢃ 4.03 (m, 4H, 6 -CH2, 1 -H,
2
0
3
(
-H), 3.74 ꢃ 3.58 (m, 3H, 2-H, 4-H, 5 -H), 3.51 ꢃ 3.41 (m, 1H, 5-H), 2.01
s, 3H, COCH ), 1.97 (s, 3H, COCH ), 1.94 (s, 3H, COCH ), 1.72 (s, 3H,
3 3 3
1
3
COCH ), 1.10 (d, J ¼ 6.4 Hz, 3H, 6-CH ); C NMR (100 MHz, CDCl3)
3
3
d ¼ 170.8, 170.7, 170.43, 170.38, 169.33, 169.29, 169.2, 169.1, 137.9, 128.44,
1
9
7
7
6
1
6
28.39, 128.36, 128.3, 128.2, 128.14, 128.12, 128.0, 127.9, 102.2, 101.5,
8.74, 98.67, 98.65, 96.2, 92.7, 79.5, 79.42, 79.37, 77.4, 77.3, 77.14, 77.05,
6.9, 76.7, 76.5, 75.7, 75.5, 75.2, 75.03, 75.0, 74.96, 74.1, 73.3, 73.23, 73.20,
2.13, 72.10, 72.0, 71.8, 71.6, 70.7, 70.6, 70.4, 68.3, 68.2, 66.6, 63.7, 63.5,
2.1, 62.0, 61.8, 58.9, 43.8, 29.7, 20.71, 20.69, 20.66, 20.58, 20.56, 20.5, 16.8,
þ
þ
6.7, 16.61, 16.57; HR-ESI-MS m/z: [M þ Na] Calcd for C H N O Na
2
7
35 3 13
32.2062; Found 632.2039.
N-Benzyl-N-benzyloxycarbonyl-3-aminopropyl 2-azido-3-O-(2-azido-4-
O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-2-deoxy-a-L-

1
8
C. QIN ET AL.
fucopyranosyl)-4-O-benyzl-2-deoxy-b-D-fucopyranoside (2). To a stirring
solution of hemiacetal 27 (70 mg, 0.115 mmol) and 2,2,2-trifluoro-N-phe-
ꢂ
nylacetimidoyl chloride (0.1 mL, 0.617 mmol) at 0 C, DBU (30 lL,
0
.201 mmol) was added. The reaction was continued at room temperature
ꢂ
for 20 h and then concentrated in vacuo under 30 C. The residue was puri-
fied by column chromatography (petroleum ether: ethyl acetate 2.5: 1 v/v)
to give disaccharide donor 3 (82 mg, 0.105 mmol, 91%).
Disaccharide donor 3 (40 mg, 0.051 mmol) and D-fucosyl acceptor 4
(
50 mg, 0.089 mmol) was dissolved in anhydrous DCM (0.9 mL) and 4 Å
MS, anhydrous diethyl ether (2.7 mL) and thiophene (0.9 mL) was added.
This mixture was stirred at room temperature for 30 min and then cooled
ꢂ
to 0 C. TMSOTf (5 lL, 0.028 mmol) was added and the solution was con-
tinued for 5 h at room temperature. After that, the solution was quenched
with Et N (0.5 mL) and filtered. The filtrate was concentrated and the
3
resulting residue was purified by column chromatography (petroleum ether:
2
0
ethyl acetate 3: 1 v/v) to give 2 (50 mg, 0.043 mmol, 84%, a-only). [a]
¼
D
ꢂ
1
ꢃ44.5 (c ¼ 1.00, CHCl ); H NMR (400 MHz, CDCl ) d ¼ 7.41 ꢃ 7.19 (m,
3
3
0
2
0H, Ar-H), 5.30 ꢃ 5.04 (m, 6H, PhCH , 1 -H, 2”-H, 3”-H, 4”-H) , 4.83 (d,
2
J ¼ 11.1 Hz, 1H, PhCH ), 4.77–4.75 (m, 3H, PhCH , 1”-H), 4.55 ꢃ 4.50 (m,
2
2
2
4
H, NPhCH ), 4.42 (d, J ¼ 11.0 Hz, 1H, PhCH ), 4.33 ꢃ 4.21 (m, 1H, 6”-H),
2
2
0
.18 (d, J ¼ 7.0 Hz, 1H, 1-H), 4.07 (m, 2H, 3 -H, 6”-H), 4.00-3.88 (m, 1H,
0
linker-OCH ), 3.81 (t, J ¼ 9.0 Hz, 1H, 2-H), 3.79 ꢃ 3.67 (m, 2H, 5 -H, 5”-
2
0
H), 3.62 (dd, J ¼ 10.7, 3.7 Hz, 1H, 2 -H), 3.53 ꢃ 3.26 (m, 6H, linker-OCH ,
2
0
linker-NCH , 3-H, 4H, 4 -H), 2.04 (s, 6H, 2COCH ), 2.00 (s, 3H, COCH ),
2
3
3
1
6
.96 ꢃ 1.81 (m, 2H, linker-CH ), 1.80 (s, 3H, COCH ), 1.30 (d, J ¼ 6.7, 3H,
2
3
0
13
-CH ), 1.10 (d, J ¼ 6.4 Hz, 3H, 6 -CH ); C NMR (100 MHz, CDCl )
3
3
3
d ¼ 170.7, 170.4, 169.2, 169.0, 138.5, 137.9, 137.8, 128.5, 128.44, 128.38,
1
7
5
27.99, 127.96, 127.89, 127.86, 127.8, 127.6, 127.3, 102.4, 100.5, 99.6, 79.2,
9.1, 77.2, 75.31, 75.26, 73.3, 72.3, 72.0, 70.7, 68.0, 67.5, 67.2, 63.6, 61.8,
8.3, 50.9, 49.8, 44.8, 43.7, 29.7, 28.5, 28.1, 23.4, 20.7, 20.6, 17.0, 16.5; HR-
þ
þ
ESI-MS m/z: [M þ Na]
Calcd for C H N O Na
1174.4591;
5
8
69 7 18
Found 1174.4626.
N-Benzyl-N-benzyloxycarbonyl-3-aminopropyl
2-acetamido-3-O-(2-
acetamido-4-O-benzyl-3-O-(2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyl)-2-
deoxy-a-L-fucopyranosyl)-4-O-benyzl-2-deoxy-b-D-fucopyranoside (28).
Trisaccharide 2 (30 mg, 0.026 mmol) was dissolved in a mixture of dry
ꢂ
pyridine (0.5 mL) and thioacetic acid (0.5 mL) at 0 C. After stirring for
12 h, the mixture was co-evaporated with toluene three times and then
purified by column chromatography (DCM: MeOH 50: 1 v/v) to give 28
2
0
ꢂ
1
(
(
30 mg, 0.025 mmol, 96%). [a]D ¼ 49.5 (c ¼ 1.00, CHCl ); H NMR
3
400 MHz, CDCl ) d ¼ 7.80 ꢃ 6.90 (m, 20H, Ar-H), 6.83 (d, J ¼ 8.1 Hz, 1H,
3
0
N-H), 6.18 (d, J ¼ 9.2 Hz, 1H, N-H), 5.27 ꢃ 5.13 (m, 3H, 3 ’-H, PhCH ),
2

JOURNAL OF CARBOHYDRATE CHEMISTRY
19
0
0
0
5
.10 ꢃ 4.99 (m, 2H, 1 -H, 4 ’-H), 4.96 (t, J ¼ 8.7 Hz, 1H, 2 ’-H), 4.88 (d,
J ¼ 11.1 Hz, 1H, PhCH ), 4.84 ꢃ 4.79 (m, 1H, PhCH ), 4.74 (d, J ¼ 15.5 Hz,
2
2
0
0
2
1
H, PhCH ), 4.63 (d, J ¼ 8.0 Hz, 3H, 1 ’-H, 3-H, 2 -H), 4.41 (d, J ¼ 10.9 Hz,
2
0
H, PhCH ), 4.34 ꢃ 4.25 (m, 2H, 6 ’-H, 1-H), 4.25 ꢃ 4.13 (m, 2H, 2-H,
2
0
0
0
PhCH ), 4.09 (t, J ¼ 9.0 Hz, 1H, 6 ’-H), 4.01-3.76 (m, 5H, 5 -H, 4-H, 3 -H,
2
0
linker-OCH , linker-NCH ), 3.66 (dd, J ¼ 9.7, 6.0 Hz, 1H, 5 ’-H),
2
2
0
3
(
3
.60 ꢃ 3.52 (m, 1H, 3-H), 3.44 (d, J ¼ 7.3 Hz, 2H, 5-H, 4 -H), 3.34 ꢃ 3.08
m, 1H, linker-OCH ), 2.87 (dt, J ¼ 14.3, 5.0 Hz, 1H, linker-NCH ), 2.14 (s,
2
2
H, COCH ), 2.09 (s, 3H, COCH ), 2.06 (s, 3H, COCH ), 2.00 (s, 3H,
3 3 3
COCH ), 1.89 (s, 3H, COCH ), 1.80 (s, 3H, COCH ), 1.68 (d, J ¼ 9.6 Hz,
3
3
3
0
2
6
1
1
1
7
2
H, linker-CH ), 1.32 (d, J ¼ 6.3 Hz, 3H, 6 -CH ), 1.17 (d, J ¼ 6.5 Hz, 3H,
2
3
13
-CH ); C NMR (100 MHz, CDCl ) d ¼ 171.6, 171.1, 170.8, 170.4, 169.3,
3
3
68.8, 156.6, 138.8, 138.2, 138.0, 137.4, 136.9, 128.7, 128.6, 128.51, 128.47,
28.4, 128.2, 128.1, 128.0, 127.9, 127.80, 127.76, 127.71, 127.65, 127.5,
27.3, 127.2, 126.4, 101.2, 100.8, 99.7, 80.0, 79.7, 78.9, 77.8, 77.2, 75.1, 73.2,
2.2, 72.1, 70.7, 68.2, 67.5, 67.3, 65.8, 62.0, 52.2, 49.7, 47.6, 42.5, 31.9, 29.7,
þ
6.9, 23.3, 20.8, 20.58, 20.56, 17.2, 16.7; HR-ESI-MS m/z: [M þ Na] Calcd
þ
for C H N O Na 1206.4998; Found 1206.4976.
5
8
69 7 18
3-Aminopropyl 2-acetamido-3-O-(2-acetamido-3-O-(-b-D-glucopyrano-
syl)-2-deoxy-a-L-fucopyranosyl)-2-deoxy-b-D-fucopyranoside (1).
Compound 28 (22 mg, 0.019 mmol) was dissolved in MeOH (5 mL) and
NaOMe (10 mg, 0.185 mmol) was added. After stirring at room temperature
þ
for 2 h, the reaction was treated with Amberlite IR120 H resin. After filtra-
tion, the filtrate was concentrated in reduced pressure and purified by col-
umn chromatography (DCM: MeOH 10: 1 v/v) to afford deacetylated
2
0
ꢂ
compound 28a (18 mg, 0.018 mmol, 95%). [a]D ¼ ꢃ16.3 (c ¼ 1.00,
1
CHCl ); H NMR (400 MHz, CDCl ) d ¼ 7.60 ꢃ 7.13 (m, 20H, Ar-H), 7.12
3
3
(
d, J ¼ 7.3 Hz, 1H, N-H), 6.69 (d, J ¼ 9.8 Hz, 1H, N-H), 5.23 (d, J ¼ 12.6 Hz,
1
H, PhCH ), 5.15 (d, J ¼ 12.4 Hz, 1H, PhCH ), 5.05 (d, J ¼ 12.3 Hz, 1H,
2
2
0
PhCH ), 4.96 ꢃ 4.83 (m, 2H, 1 -H, PhCH ), 4.79 (d, J ¼ 15.7 Hz, 1H,
2
2
0
PhCH ), 4.72 (d, J ¼ 12.2 Hz, 1H, PhCH ), 4.66 ꢃ 4.49 (m, 2H, PhCH , 2 -
2
2
2
H), 4.36 (s, 1H, OH), 4.28 (d, J ¼ 9.5 Hz, 1H, 2-H), 4.22 (d, J ¼ 16.0 Hz,
0
1
4
3
H, PhCH ), 4.03 (d, J ¼ 7.3 Hz, 2H,1 ’-H, linker-NCH ), 4.00 ꢃ 3.84 (m,
2
2
0
0
0
H, 3 -H, 1-H, 6 -H, linker-OCH ), 3.72 (dd, J ¼ 12.5, 6.1 Hz, 1H, 6 -H),
2
0
0
0
.64 (q, J ¼ 6.7 Hz, 1H, 5-H), 3.42 (m, 4H, 5-H, 2 -H, 3 -H, 4 -H), 3.33 (d,
0
0
J ¼ 4.6 Hz, 1H, 3-H), 3.31 ꢃ 3.19 (m, 2H, 4 -H, 5 -H), 3.15 (td, J ¼ 9.7,
.0 Hz, 1H, linker-OCH ), 2.88 ꢃ 2.74 (m, 1H, linker-NCH ), 2.09 (s, 3H,
4
2
2
COCH ), 1.96 (s, 3H, COCH ), 1.72 ꢃ 1.57 (m, 2H, linker-CH ), 1.32 (s,
3
3
2
1
3
J ¼ 6.4, 3H, 6-CH ), 1.03 (s, J ¼ 6.3, 3H, 6-CH ); C NMR (100 MHz,
3
3
CDCl ) d ¼ 173.0, 172.7, 156.8, 138.9, 138.6, 137.1, 136.8, 128.8, 128.6,
3
1
7
28.4, 128.14, 128.05, 127.6, 127.5, 127.34, 127.26, 127.1, 101.4, 99.9, 82.1,
9.5, 76.3, 75.3, 74.6, 74.3, 74.1, 72.8, 71.7, 70.9, 67.7, 67.6, 65.6, 62.6, 52.0,

2
0
C. QIN ET AL.
þ
4
9.5, 48.1, 42.0, 29.7, 26.7, 23.5, 17.5, 16.8; HR-ESI-MS m/z: [M þ Na]
þ
Calcd for C H N O Na 1038.4570; Found 1038.4538.
6
2
77 3 20
The deacetylated trisaccharide 28a (10 mg, 9.84 mmol) was dissolved in a
mixture of H O/DCM/MeOH (1: 1: 5 v/v/v), two drops of acetic acid were
2
added. The solution was purged with nitrogen, 10% Pd/C was added and
the solution was purged with H for 5 min, then stirred under an H
2
2
atmosphere overnight. The mixture was filtered (celite) and concentrated.
The residue was purified with a Sep-Pak cartridge C18 (Macherey-Nagel,
D u€ ren, Germany) using water and methanol as eluents to give 1 as white
1
solid (6 mg, 9.81 mmol, quant.). H NMR (400 MHz, D O) d ¼ 5.03 (s, 1H,
2
0
0
1
2
3
-H), 4.51 (d, J ¼ 7.9 Hz, 1H, 1 -H), 4.37 (d, J ¼ 8.4 Hz, 1H, 1-H), 4.17 (s,
0
0
0
H, 4-H, 2 -H), 4.07 (q, J ¼ 6.6 Hz, 1H, 5 -H), 4.02 (s, 1H, 3 -H),
0
00
.99 ꢃ 3.86 (m, 4H, 2-H, 4 -H, 6 -H, linker-OCH ), 3.80 ꢃ 3.75 (m, 1H, 5-
2
H), 3.67 (ddt, J ¼ 16.6, 10.9, 6.0 Hz, 3H, 3-H, 6”-H, linker-OCH ), 3.46 (m,
2
0
0
00
00
2
H, 3 -H, 5 -H), 3.34 (t, J ¼ 9.3 Hz, 1H, 4 -H), 3.26 (t, J ¼ 8.6 Hz, 1H, 2”-
H), 3.05 (t, J ¼ 6.9 Hz, 2H, linker-NCH ), 2.00 (s, 3H, COCH ), 1.98 (s, 3H,
2
3
COCH ), 1.91 (t, J ¼ 6.4 Hz, 2H, linker-CH ), 1.23 (d, J ¼ 6.9 Hz, 3H, 6-
3
2
13
0
CH ), 1.21 (d, J ¼ 6.8 Hz, 3H, 6 -CH );
C NMR (100 MHz, D O)
2
3
3
d ¼ 174.4, 174.2, 101.5, 100.2, 98.9, 76.5, 76.0, 75.5, 74.8, 72.8, 70.6, 70.3,
6
9.6, 68.4, 67.9, 66.9, 60.8, 51.3, 47.9, 37.6, 26.6, 24.4, 22.20, 15.4, 15.3; HR-
þ
þ
ESI-MS m/z: [M þ Na]
Calcd for C H N O Na
634.2794;
2
5
45 3 14
Found 634.2789.
Supplemental material
NMR spectra for all pure products. This material is available free of charge
via the Internet https://www.tandfonline.com/toc/lcar20/current.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This work was supported by the [National Natural Science Foundation of China] under
Grant [number 21877052, 21907039]; [Natural Science Foundation of Jiangsu Province]
under Grant [number BK20180030, BK20190575]; [National First-class Discipline Program
of Light Industry Technology and Engineering] under Grant [number LITE2018-14]; [Max
Planck Society International Partner Group Program]; [China Scholarship Council (CSC)]
and [Open Project of Key Laboratory of Carbohydrate Chemistry and Biotechnology
(
Jiangnan University), Ministry of Education] under Grant [number KLCCB-KF202005].
P.H.S. thanks the Max-Planck Society for generous financial support.

JOURNAL OF CARBOHYDRATE CHEMISTRY
21
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