Synthesis of Neu5Ac-Gal-functionalized gold glyconanoparticles

Article abstract of DOI:10.1016/j.carres.2009.06.039

Neu5Ac-Gal-containing neoglycoside 1 was convergently synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition of methyl (6-azidohexyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-O-α-d-glycero-d-galacto-2-nonulopyranosyl)uronate and 11-thioacety

Full text of DOI:10.1016/j.carres.2009.06.039

Carbohydrate Research 344 (2009) 2083–2087
Contents lists available at ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Note
Synthesis of Neu5Ac-Gal-functionalized gold glyconanoparticles
Lei Zhang a,b, Guohua Wei a, Yuguo Du a,b,
*
a State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing 100085, China
b College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Neu5Ac-Gal-containing neoglycoside 1 was convergently synthesized through Cu(I)-catalyzed 1,3-dipo-
Received 22 April 2009
Received in revised form 24 June 2009
Accepted 25 June 2009
lar cycloaddition of methyl (6-azidohexyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,5-dideoxy-2-O-
ro- -galacto-2-nonulopyranosyl)uronate and 11-thioacetylundecyl 2,4,6-tri-O-benzoyl-3-O-propargyl-b-
-galactopyranoside. The stable and water-soluble gold glyconanoparticle 2 (d = 3.4 nm) has been suc-
cessfully prepared from neoglycoside 1 and characterized by NMR, IR, and TEM techniques.
Ó 2009 Elsevier Ltd. All rights reserved.
a-D-glyce-
D
D
Available online 1 July 2009
Keywords:
Sialic acid
Gold glyconanoparticles
Carbohydrate antigen
Click chemistry
The well-known cluster glycoside effect1 has spawned the
construction of myriad multivalent glycopolymers for the study
of carbohydrate–protein interactions. Integrated nanoparticle–bio-
molecule multifunctional systems constitute useful tools to mimic
the behavior of biomolecules in cells, thus helping to explore the
mechanisms of biological process with a variety of potential appli-
cations.2,3 Gold nanoclusters functionalized with carbohydrates
provide a well-defined chemical composition to intervene in the
cell–cell adhesion and recognition processes where carbohydrates
are involved.4–8 However, assembly of glyconanoparticles from
authentic oligosaccharides are rather difficult due to the insuffi-
cient quantities and methodology limitations, while the syntheses
of these oligosaccharides are complex and often feature low overall
yields.9 The mission may be considerably simplified if target struc-
tures are represented by pseudo-oligosaccharides or oligosaccha-
ride mimics in which certain glycosidic bonds are substituted
with non-glycosidic motifs.10–14 Among these efforts, 1,2,3-triazole
links have emerged as a popular bridging unit in carbohydrate
chemistry because of their facile and efficient method of synthesis,
which is referred to as ‘click chemistry’.15,16 This method is based
on Cu(I)-catalyzed Huisgen’s 1,3-dipolar cycloaddition17 of azides
and terminal alkynes, and it has been successfully applied for the
synthesis of various glycoconjugates including multivalent glyco-
sides,18,19 cyclodextrin analogues,20 glycopeptide mimetics,21 and
glycosidase inhibitors.22 Moreover, the triazole core is more than
a passive linker because it can participate in hydrogen-bonding
and dipole interactions, which can favor the binding to biomolecu-
lar targets and improve solubility.23 In a collaborative project, we
were asked to provide neoglycoside 1 and its corresponding gold
glyconanoparticle 2 (Fig. 1) as the references for bioactivity studies.
We here report the synthesis of this Neu5Ac-Gal-coated gold
nanoparticle.
The synthesis was first envisaged from the p-methoxyphenyl
glycoside 324 (Scheme 1). Deacetylation of 3 with NaOMe in MeOH
(?4), followed by regioselective propargylation of 3-OH via a dibu-
tyltin intermediate, gave the corresponding 3-O-propargyl galacto-
pyranoside 5 in 80% yield. Benzoylation of 5 with BzCl in pyridine
and subsequent conversion of anomeric p-methoxyphenyl (MP)
group to trichloroacetimidate were carried out smoothly in the
presence of ceric ammonium nitrate (CAN), generating glycosyl do-
nor 7 in a yield of 82.8% from 5.25 Glycosylation of 7 with 11-thio-
acetylundecanol using TMSOTf as promoter afforded 8 in 95%
yield.26 Convergently, glycosylation of 927 with 6-azido-1-hexanol
in the presence of NIS and TMSOTf at ꢀ40 °C gave 10 in 70% yield.
The presence of an
by its 1H NMR spectrum, which was comparable with the NMR sig-
nals of an
-linked sialic acid moiety in earlier reports.28–30 In the
1H NMR spectrum of compound 10, a doublet of doublets at d 2.57
a-linked sialic acid moiety in 10 was supported
a
(dd, 1H, J 12.8, 4.9 Hz, H-3e) indicated the a-stereochemistry of the
C-2 of sialic acid moiety.
‘Click chemistry’ of azide 10 and alkyne 8 was induced by CuSO4
and sodium ascorbate in 1:1 H2O–THF at 50–60 °C,31 generating
the desired 1,2,3-triazole 11 in 92% yield (Scheme 2). Saponifica-
tion of 11 with a catalytic amount of NaOMe in MeOH, followed
by in situ O2 oxidation, methyl ester deletion in aq NaOH, neutral-
ization with Amberlite IR-120 (H+), and purification on a Sephadex
LH-20 column, afforded neoglycoside 1 in 80% yield. Treatment of 1
* Corresponding author. Tel.: +86 10 62849126; fax: +86 10 62923563.
E-mail address: duyuguo@rcees.ac.cn (Y. Du).
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.06.039

2084
L. Zhang et al. / Carbohydrate Research 344 (2009) 2083–2087
OH
HO
OH
OH
OH
O
COOH
O
O
HO
N
N
O
O
S
9
AcHN
N
2
OH
1
O
S
O
2
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
O
S
S S
S
O
S
S
O
O
S
S
S
O
S
S
O
O
2
Figure 1. Neoglycoside 1 and gold glyconanoparticle 2.
with NaBH4 and HAuC4, according to a reported procedure,32 fur-
nished glyconanoparticle 2, which was characterized by 1H NMR,
and FTIR spectroscopy, and transmission electron microscopy
(TEM, Fig. 2). The mean diameter of the generated particles is
3.4 nm, corresponding to an average number of 976 gold at-
mos.33,34 The bioactivity of compounds 1 and 2 is currently under
investigation by our collaborators, and the results will be disclosed
in due course.
10ꢀ1 deg cm2 gꢀ1 1H NMR and 13C NMR spectra were recorded
.
with a Bruker ARX 400 spectrometer for the solutions in CDCl3,
DMSO-d6, CD3OD, or D2O. The chemical shifts are given in ppm
downfield from internal Me4Si. Mass spectra were measured using
a MALDI-TOF mass spectrometer with
a-cyano-4-hydroxycin-
namic acid (CCA) as matrix. FTIR spectra were recorded using a
Perkin–Elmer 1720X spectrophotometer by the standard KBr tech-
nique. TLC was performed on silica gel HF254 with detection by
charring with 30% (v/v) H2SO4 in MeOH or in some cases by a UV
lamp. Column chromatography was conducted by elution of a col-
umn of silica gel (100–200 mesh) with EtOAc–petroleum ether
(60–90 °C) as the eluent. The solutions were concentrated at
<60 °C under reduced pressure. For TEM examinations, a single
drop of the aq solution (ca. 0.1 mg/mL) of the gold glyconanoparti-
cles was placed onto a copper grid coated with a carbon film. The
grid was left to dry in air for several hours at room temperature.
1. Experimental
1.1. General methods
Optical rotations were determined at 25 °C with a Perkin–Elmer
model 241-Mc automatic polarimeter; [a]D-values are in units of
OR
OR
OR
OR
O
O
b
d
OMP
OMP
O
RO
OR
OR
3 R = Ac
4 R = H
5 R = H
6 R = Bz
a
c
OBz
OBz
OBz
OBz
O
O
e
f
O
O
SAc
9
O
OBz
OC(NH)CCl3
OBz
7
8
OAc
OAc
AcO
SPh
OAc
OAc
O
COOMe
O
AcO
AcO
O
N3
COOMe
AcHN
AcHN
AcO
10
9
Scheme 1. Reagents and conditions: (a) MeONa, MeOH, rt; (b) (i) MeOH, Bu2SnO, reflux, (ii) propargyl bromide, Bu4NI, toluene, 60 °C, 80%; (c) Pyr, BzCl, DMAP, 92%; (d) (i)
CAN, 4:1 CH3CN–H2O; (ii) Cl3CCN, DBU, CH2Cl2, 90% from 6; (e) 11-thioacetylundecanol, TMSOTf, CH2Cl2, 0 °C, 95%; (f) 6-azido-1-hexanol, NIS, TMSOTf, 1:1 CH2Cl2–CH3CN,
ꢀ40 °C, 70%.

L. Zhang et al. / Carbohydrate Research 344 (2009) 2083–2087
2085
OAc
OBz
OAc
O
OBz
COOMe
O
AcO
O
N3
+
O
SAc
9
O
AcHN
OBz
AcO
a
10
8
OBz OBz
OAc
OAc
O
COOMe
O
O
AcO
N
N
O
O
SAc
9
AcHN
N
OBz
AcO
11
b
c
O
2
1
S
O
2
Scheme 2. Reagents and conditions: (a) CuSO4ꢃ5H2O, sodium ascorbate, 1:1 THF–H2O, 92%; (b) NaOMe, MeOH; O2, 24 h at rt; then H2O, 80%; (c) NaBH4, HAuC4, Milli-Q water.
TEM analysis was carried out in a Hitachi H-7500 microscope
working at 200 kV.
C16H20O7: C, 59.25; H, 6.22. Found: C, 59.04; H, 6.28. MALDI-TOF-
MS: calcd for C16H20O7: 324.12 [M]+; found: 347.23 [M+Na]+.
1.2. p-Methoxyphenyl 3-O-propargyl-b-
D-galactopyranoside (5)
1.3. p-Methoxyphenyl 2,4,6-tri-O-benzoyl-3-O-propargyl-b-D-
galactopyranoside (6)
To a solution of 3 (10.5 g, 23.1 mmol) in anhyd MeOH (100 mL)
was added 1 N NaOMe in MeOH until pH 9.5. The mixture was stir-
red at rt for 5 h, then neutralized with Amberlite IR-120 (H+) and
filtered. The filtrate was concentrated to dryness, and the resulting
compound 4 was used without further purification. After refluxing
To a solution of 5 (1.81 g, 5.58 mmol) in pyridine (10 mL) were
added BzCl (2.32 mL, 19.9 mmol) and DMAP (30 mg) at 0 °C. The
reaction mixture was stirred at rt for 4 h, then quenched by adding
MeOH (1 mL), and concentrated under diminished pressure. The
residue was redissolved in CH2Cl2 and was washed successively
with 1 N HCl (aq), aq NaHCO3, and brine. The organic phase was
dried over Na2SO4, and concentrated. Purification of the residue
by column chromatography on silica gel (1:3 EtOAc–petroleum
of
4 (5.521 g, 19.28 mmol) and dibutyltin oxide (5.299 g,
21.26 mmol) in anhyd MeOH (85 mL) under a nitrogen protection
for 4 h, the reaction mixture was concentrated under vacuum.
The dried residue was suspended in toluene (136 mL) under nitro-
gen atmosphere, and propargyl bromide (4.6 mL, 23.19 mmol) and
tetrabutylammonium iodide (7.11 g, 19.28 mmol) were added
with vigorous stirring at 60 °C for 18 h. At the end of this time,
TLC indicated that all starting materials were consumed, and the
solvent was then evaporated. The residue was purified by silica
ether) afforded 6 (3.26 g, 92%) as an amorphous solid: ½a D25
ꢁ
+ 72
(c 0.6, CHCl3); 1H NMR (400 MHz, CDCl3): d 2.34 (t, 1H, J 2.3 Hz,
„CH), 3.71 (s, 3H, OMe), 4.20–4.27 (m, 4H, H-3, H-5, and OCH2),
4.54 (dd, 1H, J 11.5, 5.2 Hz, H-6a), 4.61 (dd, 1H, J 11.5, 7.8 Hz, H-
6b), 5.15 (d, 1H, J 8.0 Hz, H-1), 5.74 (dd, 1 H, J 9.9, 8.0 Hz, H-2),
5.87 (br d, 1H, J 2.8 Hz, H-4), 6.65, 6.95 (2d, 2 ꢂ 2H, C6H4), 7.44–
8.18 (m, 15H, 3Ph). Anal. Calcd for C37H32O10: C, 69.80; H, 5.07.
gel column chromatography (8:1 EtOAc–MeOH) to afford
5
(5.01 g, 80%) as an amorphous white solid: ½a D25
ꢀ 8 (c 1, CHCl3);
ꢁ
1H NMR (400 MHz, CD3OD): d 2.86 (t, 1H, J 2.4 Hz, „CH), 3.57
(dd, 1H, J 9.7, 3.2 Hz, H-3), 3.62 (br d, 1H, J 5.9 Hz, H-6a), 3.73–
3.76 (m, 5H, H-5, H-6b, and OCH3), 3.84 (dd, 1H, J 9.7, 7.8 Hz, H-
2), 4.11 (br d, 1H, J 3.1 Hz, H-4), 4.38–4.40 (m, 2H, OCH2), 4.75
(d, 1H, J 7.8 Hz, H-1), 6.82, 7.05 (2d, 2 ꢂ 2H, C6H4). Anal. Calcd for
Found: C, 69.62; H, 5.14. MALDI-TOFMS: calcd for C37H32O10
:
636.20 [M]+; found: 659.27 [M+Na]+.
1.4. 2,4,6-Tri-O-benzoyl-3-O-propargyl-b-D-galactopyranosyl
trichloroacetimidate (7)
To a solution of 6 (637 mg, 1 mmol) in CH3CN (16 mL) and H2O
(4 mL) was added ammonium cerium nitrate (1.64 g, 3.0 mmol) at
rt. After stirring for 1.5 h, the reaction mixture was diluted with
EtOAc and H2O. The organic layer was washed with brine, dried
over Na2SO4, and concentrated. Further purification was carried
out by silica gel column chromatography (1:2 EtOAc–petroleum
ether) to give a yellowish amorphous solid. To a solution of the
above solid (516 mg) in CH2Cl2 (3 mL) were added trichloroaceto-
nitrile (0.3 mL, 3 mmol) and DBU (30 lL) at rt. After stirring for 3 h,
the reaction mixture was concentrated, and the residue was puri-
fied by silica gel column chromatography (1:4 EtOAc–petroleum
ether) to give 7 (594 mg, 90%) as an amorphous white solid:
½
a 2D5 + 11 (c 0.75, CHCl3); 1H NMR (400 MHz, CDCl3): d 2.45 (t,
ꢁ
1H, J 2.4 Hz, „CH), 4.27 (dd, 1H, J 16.4, 2.3 Hz, OCH2), 4.48 (dd, 1
H, J 16.4, 2.3 Hz, OCH2), 4.52 (dd, 1H, J 11.4, 5.5 Hz, H-6a), 4.55
(dd, 1H, J 11.4, 7.0 Hz, H-6b), 4.66 (dd, 1H, J 10.3, 3.3 Hz, H-3),
4.70 (dd, 1H, J 5.5, 7.0 Hz, H-5), 5.67 (dd, 1H, J 10.3, 3.7 Hz, H-2),
6.02 (d, 1H, J 2.6 Hz, H-4), 6.84 (d, 1H, J 3.7 Hz, H-1), 7.41–8.14
(m, 15H, 3Ph), 8.57 (s,
1 H, NH). MALDI-TOFMS: calcd for
C32H26Cl3NO9: 673.07 [M]+; found: 695.16 [M+Na]+.
Figure 2. TEM of 2 shows the uniform size and dispersion of the particles.

2086
L. Zhang et al. / Carbohydrate Research 344 (2009) 2083–2087
1.5. 11-Thioacetylundecyl 2,4,6-tri-O-benzoyl-3-O-propargyl-b-
(400 MHz, CDCl3): d 1.05–1.52 (m, 26H), 1.85, 1.95 1.99, 2.01,
2.29 (5s, 15H), 2.10 (t, 4H, J 5.3 Hz), 2.55 (dd, 1H, J 12.8, 4.8 Hz),
2.83 (t, 2H, J 7.3 Hz), 3.22–3.24 (m, 1H), 3.45–3.47 (m, 1H), 3.75
(s, 3H), 3.88 (t, 1H, J 3.8 Hz), 4.07–4.10 (m, 7H), 4.33 (dd, 1H, J
12.8, 1.8 Hz), 4.60–4.63 (m, 2H), 4.81–4.83 (m, 2H), 5.29 (dd, 1H,
J 10.7, 2.1 Hz), 5.35 (br d, 1H, J 5.8 Hz), 5.43–5.45 (m, 2H), 5.84
(br d, 1H, J 8.6 Hz), 7.41–8.13 (m, 16H); 13C NMR (100 MHz, CDCl3):
d 21.3, 21.4, 21.5, 21.6, 23.6, 23.7, 25.6, 25.7, 26.3, 29.4, 29.6, 29.7,
29.9, 30, 31.2, 38.1, 38.6, 49.8, 49.9, 53.1, 53.2, 62.8, 62.9, 63, 63.1,
62.2, 65.2, 67.9, 69, 69.4, 69.5, 69.7, 70.9 72.3, 72.6, 77.3, 77.7, 78,
99.1, 102.1, 129, 129.1, 130.2, 130.4, 130.6, 133.7, 133.8, 134,
165.7, 166.4, 166.6, 168.2, 170.6, 170.7, 171.1, 171.2, 171.3,
196.6. Anal. Calcd for C69H90N4O23S: C, 60.25; H, 6.59. Found: C,
60.39; H, 6.67. MALDI-TOFMS: calcd for C69H90N4O23S: 1374.57
[M]+; found: 1397.46 [M+Na]+.
D-galactopyranoside (8)
To a mixture of 7 (290 mg, 0.438 mmol), 11-thioacetylundeca-
nol (90.14 mg, 0.366 mmol), and 4 Å molecular sieves (100 mg)
in anhyd CH2Cl2 (5 mL) was added TMSOTf (7.94 L, 0.044 mmol)
l
at 0 °C under an N2 atmosphere. The reaction mixture was stirred
under these conditions for 1.5 h, then neutralized with Et3N and fil-
tered. The filtrate mixture was concentrated to dryness. The resi-
due was purified by silica gel column chromatography (1:3
EtOAc–petroleum ether) to give 8 (594 mg, 95%) as an amorphous
solid: ½a 2D5
ꢁ
+ 127 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3): d 1.08–
1.19 (m, 18H, 9 CH2), 2.32 (s, 3H, OAc), 2.33 (t, 1H, J 2.4 Hz,
„CH), 2.85 (t, 2H, J 7.2 Hz, CH2S), 3.49–3.53 (m, 1H, OCH2), 3.92–
3.96 (m, 1H, OCH2), 4.15–4.20 (m, 3H, H-3, H-5, and one proton
of OCH2C„CH), 4.29 (dd, 1H, J 16.6, 2.4 Hz, another proton of
OCH2C„CH), 4.41 (dd, 1H, J 11.3, 6.3 Hz, H-6a), 4.63 (dd, 1H, J
11.3, 6.7 Hz, H-6b), 4.70 (d, J 8.0 Hz, H-1), 5.48 (dd, 1H, J 10.0,
8.0 Hz, H-2), 5.84 (d, J 3.1 Hz, H-4), 8.00–8.15 (m, 15H, 3Ph). Anal.
Calcd for C43H50O10S: C, 68.05; H, 6.64. Found: C, 67.81; H, 6.59.
MALDI-TOFMS: calcd for C43H50O10S: 758.31 [M]+; found: 781.27
[M+Na]+.
1.8. 11,110-Dithiobis{undecyl [3-O-[(5-acetamido-3,5-dideoxy-
2-O-
a-
D-glycero-
D-galacto-2-nonulopyranosylhexanyl)triazol-1-
methyl]-b-
D-galactopyranoside]} (1)
To a solution of 11 (100 mg, 0.07 mmol) in anhyd MeOH
(20 mL) was added 1 N NaOMe until pH 9.5. The reaction mixture
was stirred at rt for 40 h, then a gentle stream of oxygen was bub-
bled through the solution, and stirring was continued for approxi-
mately 24 h, at the end of which time H2O (3 mL) was added. After
stirring for another 12 h, the reaction mixture was cooled to 0 °C,
neutralized with amberlite IR-120 (H+), and then filtered, and the
filtrate was evaporated. The residue was purified with Sephadex
LH-20 and the desired fractions were lyophilized to give 1
1.6. Methyl (6-azidohexyl 5-acetamido-4,7,8,9-tetra-O-acetyl-3,
5-dideoxy-2-O-a-D-glycero-D-galacto-2-nonulopyranosid)uro-
nate (10)
To a stirred mixture of 9 (250 mg, 0.4284 mmol), 6-azido-1-
hexanol (55.7 mg, 0.43 mmol), and 4Å molecular sieves (30 mg)
in dry 1:1 CH2Cl2–CH3CN (5 mL) were added NIS (131 mg,
(48.7 mg, 80%) as a white amorphous solid: ½a D25
ꢁ
+ 90 (c 0.5,
0.64 mmol) and TMSOTf (7
l
L, 0.043 mmol) at ꢀ40 °C. The reaction
H2O); 1H NMR (400 MHz, 49:1 DMSO-d6–D2O): d 1.11–1.46 (m,
26H), 1.72–1.74 (m, 2H), 1.84 (d, 3H, J 7.0 Hz), 2.59 (dd, 1H, J
10.8, 1.8 Hz), 2.61 (t, 2H, J 7.1 Hz), 3.14–3.25 (m, 3H), 3.30–3.38
(m, 3H), 3.46–3.74 (m, 5H), 3.86 (br s, 1H), 4.06 (d, 1H, J 7.7 Hz),
4.25–4.27 (m, 2H), 4.53 (dd, 1H, J 12.2, 2.1 Hz), 4.64 (d, 1H, J
12.2 Hz), 7.98 (s, 1H); 13C NMR (100 MHz, 49:1 DMSO-d6–D2O): d
28.6, 29.5, 29.9, 30, 30.2, 30.6, 39, 5, 39.7, 39.9, 40.2, 40.3, 40.6,
40.8, 50.4, 61.2, 62.4, 63, 63.2, 63.8, 64, 65.5, 69.6, 69.8, 71.4,
72.3, 72.5, 73.4, 75.8, 82.3, 101.7, 104.2, 124.7, 145.6, 172.1,
mixture was stirred under these conditions for 6 h until all starting
materials were consumed. The mixture was then neutralized with
Et3N, and filtered, and the filtrate was concentrated to dryness. The
residue was purified by silica gel column chromatography (2:1
EtOAc–petroleum ether) to give 10 (186 mg, 70%) as an amorphous
solid: ½a 2D5
ꢁ
ꢀ 12 (c 1, CHCl3); 1H NMR (400 MHz, CDCl3): d 1.35–
1.39 (m, 4H), 1.57–1.61 (m, 4H), 1.86, 2.00, 2.01, 2.06, 2.12 (5s,
15H), 2.57 (dd, 1H, J 12.8, 4.9 Hz), 3.27–3.29 (m, 3H), 3.46–3.48
(m, 1H), 3.79 (s, 3H), 3.91 (dd, 1H, J 10.5, 2.3 Hz), 4.09–4.11 (m,
2H), 4.80 (dd, 1H, J 12.3, 2.4 Hz), 5.17–5.19 (m, 1H), 5.25–5.27
(m, 1H), 5.36–5.38 (m, 1H), 5.41 (br d, 1H, J 10.0); 13C NMR
(100 MHz, CDCl3): d 18.8, 18.9, 19.1, 21.1, 23.7, 24.4, 26.7, 27.3,
35.5, 47.5, 49.4, 50.7, 60.5, 61.9, 66.6, 66.9, 69.8, 70.2, 74.8, 75.1,
75.4, 96.5, 165.6, 166.6, 168.2, 168.6, 168.8, 169.1. Anal. Calcd for
C26H40N4O13: C, 50.64; H, 6.54. Found: C, 50.51; H, 6.59. MALDI-
173.6; IR (KBr):
c = 3352, 2927, 2855, 1717, 1626, 1437, 1377,
1072, 1035 cmꢀ1. Anal. Calcd for C74H130N8O30S2: C, 53.03; H,
7.82. Found: C, 52.84; H, 7.87. MALDI-TOFMS: calcd for
C74H130N8O30S2: 1674.83 [M]; found: 1675.98 [M+H]+, 837.92
[(M+H)/2]+.
1.9. Synthesis of GNP (2)
TOFMS: calcd for C26H40N4O13
:
616.26 [M]+; found: 639.37
[M+Na]+.
To a solution of disulfide 1 (30 mg, 0.018 mmol) in Milli-Q H2O
(4 mL) was added HAuCl4ꢃ4H2O (22.11 mg). The solution was stir-
red at rt for 10 min, kept at 0 °C for 15 min, then NaBH4 (3.585 mg,
0.0087 mmol, in 0.5 mL H2O) was added in small portions under
vigorous stirring conditions. The reaction mixture turned immedi-
ately to deep brown. The mixture was kept under these conditions
for another 15 min, then warmed up to rt and stirred for further
3 h. At the end of this time, the solvent was removed by centrifu-
gation, and the black residue was redissolved in H2O (12 mL) and
purified by centrifugal filtering (40 min, 14,000 rpm). The process
was repeated three times. Finally, the H2O phase was lyophilized
to afford the gold glyconanoparticles 2 (10 mg) as a dark brown
powder. Average diameter and number of gold atoms: 3.4 nm,
976. 1H NMR (400 MHz, D2O): d 1.12–1.80 (m, 26H), 1.95–1.97
(m, 2H), 2.08–2.11 (m, 3H), 2.42 (dd, 1H, J 4.6, 1.8 Hz), 2.59 (dd,
1H, J 1.8, 2.1 Hz), 2.94 (t, 2H, J 8.3 Hz), 3.51 (br d, 1H, J 9.0 Hz),
3.59–3.96 (m, 12H), 4.16–4.19 (m, 2H), 4.48–4.50 (m, 1H), 8.10
1.7. 11-Thioacetylundecyl 3-O-[(methyl 5-acetamido-4,7,8,9-tet-
ra-O-acetyl-3,5-dideoxy-2-O- -glycero- -galacto-2-nonulopyr-
a-D
D
anosylhexanyl)triazol-1-methyl]-2,4,6-tri-O-benzoyl-b-D-galacto-
pyranoside (11)
To a suspension of 10 (266 mg, 0.43 mmol) and 8 (272 mg
0.4313 mmol) in 1:1 H2O–THF (40 mL) were added sodium ascor-
bate (34.18 mg, 0.17 mmol) and CuSO4ꢃ5H2O (21.4 mg,
0.086 mmol) under vigorous stirring. The mixture was stirred in
a dark room at 50–60 °C until complete consumption of the reac-
tants was indicated by TLC analysis. The solvent was evaporated,
and the residue was diluted with EtOAc, and washed with H2O
and brine. The aq layer was extracted with EtOAc, and the com-
bined organic layers were dried over Na2SO4 and concentrated.
Further purification was carried out by silica gel column chroma-
tography (3:1 EtOAc–petroleum ether) to give 11 (545 mg, 92%)
(s, 1H); IR (KBr):
c = 3395, 2928, 2855, 1711, 1635, 1415, 1118,
as a white amorphous solid: ½a D25
ꢁ
+ 70 (c 0.6, CHCl3); 1H NMR
1082, 1044. Found analytical data for 2: C, 23.70; H, 3.36.

L. Zhang et al. / Carbohydrate Research 344 (2009) 2083–2087
2087
13. Jiménez Blanco, J. L.; Bootello, P.; Benito, J. M.; Ortiz Mellet, C.; Garcia
Fernández, J. M. J. Org. Chem. 2006, 71, 5136–5143.
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This work was supported in partial by NNSF of China (Projects
20872172, 20732001, and 20621703).
Supplementary data
Supplementary data associated with this article can be found, in
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