Synthesis of triazole-linked glycoconjugates by copper(I)-catalyzed regiospecific cycloaddition of alkynes and azides

Article abstract of DOI:10.1080/00397910802431198

Several 1,2,3-triazole-linked glycoconjugates were efficiently synthesized via a Cu(I)-mediated 1,3-dipolar cycloaddition with high regiospecificity and yield (≥85%), providing a simple and efficient route to synthesize protected and unprotected neoglycoconjugates. Introduction of a spacer between glycosyl moieties and other compounds reduces steric hindrance, promotes yield, and expands the varieties of glycoconjugates to satisfy various needs of biological events. The structures of all the synthesized glycoconjugates were clearly confirmed by infrared(IR), 1H NMR, 13C NMR, elemental analysis (EA), or MS. Copyright Taylor & Francis Group, LLC.

Full text of DOI:10.1080/00397910802431198

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Synthesis of Triazole-Linked
Glycoconjugates by Copper(I)-
Catalyzed Regiospecific
Cycloaddition of Alkynes and
Azides
Xiaoru Zhang a , Xiaohui Yang a & Shusheng Zhang a b
a Key Laboratory of Eco-chemical Engineering,
Ministry of Education, College of Chemistry and
Molecular Engineering, Qingdao University of
Science and Technology, Qingdao, China
b Key Laboratory of Organofluorine Chemistry,
Shanghai Institute of Organic Chemistry, Chinese
Academy of Science, Shanghai, China
Published online: 29 Jan 2009.
To cite this article: Xiaoru Zhang , Xiaohui Yang & Shusheng Zhang (2009): Synthesis
of Triazole-Linked Glycoconjugates by Copper(I)-Catalyzed Regiospecific Cycloaddition
of Alkynes and Azides, Synthetic Communications: An International Journal for Rapid
Communication of Synthetic Organic Chemistry, 39:5, 830-844
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Synthetic Communications1, 39: 830–844, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910802431198
Synthesis of Triazole-Linked Glycoconjugates by
Copper(I)-Catalyzed Regiospecific Cycloaddition
of Alkynes and Azides
Xiaoru Zhang,1 Xiaohui Yang,1 and Shusheng Zhang1,2
1Key Laboratory of Eco-chemical Engineering, Ministry of Education,
College of Chemistry and Molecular Engineering, Qingdao University of
Science and Technology, Qingdao, China
2Key Laboratory of Organofluorine Chemistry, Shanghai Institute of
Organic Chemistry, Chinese Academy of Science, Shanghai, China
Abstract: Several 1,2,3-triazole-linked glycoconjugates were efficiently synthe-
sized via a Cu(I)-mediated 1,3-dipolar cycloaddition with high regiospecificity
and yield (ꢀ 85%), providing a simple and efficient route to synthesize protected
and unprotected neoglycoconjugates. Introduction of a spacer between glycosyl
moieties and other compounds reduces steric hindrance, promotes yield, and
expands the varieties of glycoconjugates to satisfy various needs of biological
events. The structures of all the synthesized glycoconjugates were clearly
confirmed by infrared(IR), 1H NMR, 13C NMR, elemental analysis (EA), or MS.
Keywords: Click chemistry, 1,3-dipolar cycloaddition, glycoconjugates, 1,2,3-
triazoles
Oligosaccharides and glycoconjugates have been shown to govern
crucial life processes and disease states,[1,2] so a lot of effort has been
made to attach sugars to scaffolds to construct neoglycoconjugates in
rapid and convenient way.[3–6] Our research efforts have been aimed at
synthesis of triazole-linked neoglycoconjugates via a mild, Cu(I)-
catalyzed procedure for the [3 þ 2] cycloaddition between organic azides
Received June 1, 2008.
Address correspondence to Shusheng Zhang, College of Chemistry and Mole-
cular Engineering, Qingdao University of Science and Technology, Qingdao
266042, China. E-mail: shushzhang@126.com
830

Triazole-Linked Glycoconjugates
831
and acetylenes, leading to a regioselective reaction toward 1,4-
disubstituted 1,2,3-triazole in high yields (‘‘click reactions’’), developed
independently by the Sharpless and Meldal groups.[7,8]
Click chemistry has been widely used in medicinal,[9] supramolecular,
and material chemistry[10] such as in dendrimers[11–13] and liquid crys-
tals.[14,15] Application of this protocol to oligosaccharides and glycocon-
jugates has recently begun, and most of the reports are concerned with
the use of anomeric azides.[16–19] Because of steric hindrance, lots of com-
pounds had low yields[13–16] which limited application of click chemistry
to oligosaccharides and glycoconjugates. Therefore, an introduction of a
spacer between the sugar moiety and lipids or peptides or other com-
pounds is required.[23,24] This will also expand structural diversity of
glycoconjugates and satisfy various needs of biological events. Based
on these facts, we designed efficient procedures to synthesize 1,2,3-
triazole-linked glycoconjugates with aromatic compounds, heterocyclic
compounds, amino acids, sterol, and steroid saponin.
In our approach, to obtain 1,4-disubstituted-1,2,3-triazole-
linked glycoconjugtes, galactose was chosen as a model of glycosyl
moiety. 2-Azidoethyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranoside (2)
and 2-propynyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranoside (3) used in
Huisgen 1,3-dipolar cycloaddition reaction were obtained by reactions
of peracetylated galactose with 2-azidoethanol or 2-propynol in the
presence of Et2O ꢁ BF3 (Scheme 1).[25,26]
Reaction of 2-azidoethyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyrano-
side (2) with p-methoxyphenyl acetylene (4a) or p-pentylphenyl acetylene
(4b) in the presence of CuI in toluene afforded exclusively the 1,4-
disubstituted 1,2,3-triazole-linked glycoconjugtes 5a and 5b in high yield,
respectively (Table 1).
Our next endeavors were devoted toward performing the Huisgen
1,3-dipolar cycloaddition reaction with 2-propynyl 2,3,4,6-tetra-O-
acetyl-b-D-galactopyranoside (3). To this end, we have synthesized
various azido moieties in three strategies as follows (Scheme 2).
Subsequently, those azides were reacted with glycosyl alkyne (3) in
the presence of CuI to produce various glycoconjugates (9a–f) as show
in Table 2. Most reactions were highly regioselective and yielded more
than 85% except the reaction between 3 and 6, in which 1,4-disubstituted
Scheme 1. Synthesis of azido and alkynyl glycoside.

832

Triazole-Linked Glycoconjugates
833
Scheme 2. Synthesis of azido moiety.
triazole was not exclusively obtained and an isomer (1,5-disubstituted
triazole) was produced, judging from NMR. It was found that the isomer
had been decreasing as the CuI increased because the ratio of integral
1
area of H NMR and the ratio of 1,4- and 1,5-disubstituted triazole
was 47:53, 63:37, and 83:17 in the presence of 0.1 eq CuI, 0.2 eq CuI,
and 0.5 eq CuI, respectively. Subsequently, the other method[24,25] was
adopted in which 9a was exclusively synthesized and yielded 88% using
the catalyst of 2 eq CuI and 3 eq N,N-diisopropylethylamine (DIPEA) in
dried toluene under room temperature for 24h, possibly because of DIPEA
promoting Cu(I) insertion into terminal alkynes.[27,28] All those target
products were confirmed by 1H NMR, 13C NMR, IR, and EA or Ms.
In addition, all products synthesized by us would be deprotected
easily in alkaline solution[25,26] without a side reaction, which could
satisfy some biological need for unprotected oligosaccharides or glyco-
conjugates. Therefore, our strategies could be comprehensively applied
to synthesize a series of protected or unprotected neoglycoconjugates.
In conclusion, we have developed a practical strategy for the liga-
tion of sugar to amino acids, lipids, and aryl and heterocyclic
compounds under mild reaction conditions with high regioselectivity.

834

835

836
X. Zhang, X. Yang, and S. Zhang
Through introduction of a spacer between the glycosyl moiety and other
compounds, steric hindrance effect was reduced, and high yields were
achieved. Therefore, this diversity-oriented synthesis opens a simple
way to build a metabolically stable triazole linkage between carbohy-
drates and other biomolecules, which can be used as new strategies for
the fast generation of small library of neoglycoconjugates.
EXPERIMENTAL
Compounds 1,[29] 2,[25] 3,[26] 5-cholesten-3b-tosylate, and 5-spirosten-
3b-tosylate[30,31] were obtained following the procedures described in
literature.
Synthesis of 5a
CuI (0.038 g, 0.1 eq) was added to a solution of compound 2 (0.83 g,
2.0 mmol) and p-methoxyphenyl acetylene (0.27 g, 1 eq) in toluene
(20 mL) and then refluxed for 2 h. At the end of the reaction as judged
by thin-layer chromatographic (TLC) analysis, the reaction solution
was concentrated, and the residue was again dissolved in ethyl acetate
(50 mL), and washed with water (3 ꢃ 50 mL). The organic phase was
dried over anhydrous sodium sulfate and subsequently filtered and con-
centrated. The crude product was purified by silica-gel column chroma-
tography to afford 5a as a slightly yellow, viscous product (1.02 g,
1
93%). IR (KBr): v=cmꢄ1 3134, 2108, 1746; H NMR (CDCl3): d=ppm
7.77 (s, 1 H), 7.75 (d, 2 H, J ¼ 9.0 Hz), 6.91 (d, 2 H, J ¼ 9.0 Hz), 5.34
(d, 1 H, J ¼ 3.0 Hz), 5.16 (dd, 1 H, J ¼ 8.0, 10.5 Hz), 4.94 (dd, 1 H,
J ¼ 3.0, 10.5 Hz), 4.52 (m, 1 H), 4.46 (m, 1 H), 4.41 (d, 1 H, J ¼ 8.0 Hz),
4.22–4.24 (m, 1 H), 4.04–4.14 (m, 2 H), 3.83–3.91 (m, 2 H), 3.81 (s, 3 H),
2.11, 1.98, 1.90, 1.67 (4 s, 12 H); 13C NMR (CDCl3): d=ppm 172.5, 170.6,
168.7, 165.9, 159.0, 147.2, 126.8, 123.0, 120.8, 113.9, 105.9, 70.1, 68.2,
67.3, 66.2, 61.0, 55.1, 50.1, 20.7. Anal. calcd. for C25H31N3O11: C,
54.64; H, 5.69; N, 7.65. Found: C, 54.59; H, 5.60; N, 5.74.
Synthesis of 5b
The compound 5b was obtained according to general procedure of com-
pound 5a and isolated as a slightly yellow, viscous product (1.08 g, 92%).
IR (KBr): v=cmꢄ1 3134, 2109, 1761; 1H NMR (CDCl3): d=ppm 7.29 (s, 1
H, J ¼ 3.0 Hz), 7.23 (d, 2 H, J ¼ 9.0 Hz), 7.19 (d, 2 H, J ¼ 9.0 Hz), 5.34

Triazole-Linked Glycoconjugates
837
(d, 1 H, J ¼ 3.0 Hz), 5.15 (dd, 1 H, J ¼ 8.0, 10.5 Hz), 4.93 (dd, 1 H,
J ¼ 3.0, 10.5 Hz), 4.59–4.65 (m, 1 H), 4.45–4.52 (m, 1 H), 4.42 (d, 1 H,
J ¼ 8.0 Hz), 4.21–4.23 (m, 1 H), 4.03–4.07 (m, 2 H), 3.82–3.91 (m, 2 H),
2.57 (t, 2 H, J ¼ 8.0 Hz), 2.10, 1.98, 1.90, 1.68 (4 s, 12 H), 1.57 (quint, 2
H, J ¼ 7.0 Hz), 1.23–1.62 (m, 4 H), 0.84 (t, 3 H, J ¼ 7.0 Hz); 13C NMR
(CDCl3): d=ppm 172.5, 170.6, 168.8, 166.1, 147.6, 142.7, 128.7, 127.9,
125.4, 120.8, 104.6, 70.6, 68.2, 67.8, 66.9, 61.0, 49.9, 35.1, 31.2, 22.3,
20.2, 14.1. Anal. calcd. for C29H39N3O10: C, 59.07; H, 6.67; N, 7.13;
Found: C, 59.10; H, 6.57; N, 7.21.
Synthesis of 6
1-(Chloromethyl)-1H-1,2,4-triazole (2.0 g, 17.1 mmol) was dissolved in
N,N-dimethylformamide (DMF) (50 mL), followed by the addition of
NaN3 (7.8 g, 0.12 mol). The heterogeneous mixture was stirred vigorously
at 60 ꢅC for 16 h. The reaction mixture was diluted with ethyl acetate
(100 mL) and washed with water (3 ꢃ 100 mL). The organic phase was
dried with anhydrous sodium sulfate, filtered, and concentrated. The resi-
due was purified by silica gel column chromatography to finally obtain a
1
slightly yellow product 6 (1.7 g, 80%). IR (KBr): v=cmꢄ1 2105; H NMR
(CDCl3): d=ppm 8.20 (s, 1 H), 7.93 (s, 1 H), 5.39 (s, 2 H). Anal. calcd. for
C3 H4 N6: C, 29.03; H, 3.25; N, 67.72. Found: C, 29.28; H, 3.21; N, 67.68.
Synthesis of 7a
Chloroacetyl chloride (0.8 mL, 1 eq) dropwise at 0 ꢅC. was added to a
solution of 1-phenylpiperazine hydrochloride (2.0 g, 10 mmol) and
triethylamine (2.8 mL, 2 eq) in anhydrous dichloromethane (50 mL).
The reaction mixture was stirred at room temperature for 2 h and mon-
itored by TLC. Then the mixture was diluted with dichloromethane
(50 mL) and washed with water (2 ꢃ 100 mL). The organic phase was
dried over anhydrous sodium sulfate and concentrated to yield a solid,
which was crystallized to obtain 2-chloroacetyl 4-phenylpiperazine
(2.2 g, 92%). 1H NMR (CDCl3): d=ppm 1H NMR (CDCl3): d=ppm
7.26–7.29 (m, 2 H), 6.89–6.93 (m, 3 H), 4.10 (s, 2 H, J ¼ 7.0 Hz), 3.78,
3.67, 3.22, 3.17 (4 t, 8 H, J ¼ 5.0 Hz).
The compound 7a was obtained according to general procedure of
compound 6 with 2-chloroacetyl 4-phenylpiperazine, and isolated as a
slightly brown solid (1.7 g, 81%). IR (KBr): v=cmꢄ1 3010, 2105, 1644;
1H NMR (CDCl3): d=ppm 7.28–7.33 (m, 2 H), 6.92–6.96 (m, 3 H), 4.02

838
X. Zhang, X. Yang, and S. Zhang
(s, 2 H), 3.82, 3.56, 3.21 (3t, 8 H,J¼ 5.0 Hz). Anal. calcd. for C12H15N5O:
C, 58.76; H, 6.16; N, 28.55. Found: C, 58.71; H, 6.13; N, 28.61.
Synthesis of 7b
The compound 7b was obtained according to general procedure of
compound 7a. First, ethyl N-(2-chloroacetyl)-glycinate was synthesized
1
and isolated as a white solid (2.3 g, 92%). H NMR (CDCl3): d=ppm
4.29 (quart, 2 H, J ¼ 7.0 Hz), 4.06–4.09 (m, 4 H), 1.30 (t, 3 H, J ¼ 7.0 Hz).
Compound 7b was obtained according to general procedure of com-
pound 6 with ethyl N-(2-chloroacetyl)-glycinate and isolated as a white
1
solid (1.5 g, 72%). IR (KBr): v=cmꢄ1 3321, 2108, 1747, 1674; H NMR
(CDCl3): d=ppm 6.87 (s, 1 H), 4.23 (quart, 2 H, J ¼ 7.0 Hz), 4.03–4.15
(m, 4 H), 1.30 (t, 3 H, J ¼ 7.0 Hz). Anal. calcd. for C6H10N4O3: C,
38.71; H, 5.41; N, 30.09; Found: C, 38.66; H, 5.44; N, 30.11.
Synthesis of 7c
The compound 7c was obtained according to general procedure of
compound 7a. First, diethyl N-(2-chloroacetyl)-L-glutamate was synthe-
sized and isolated as a white solid (2.6 g, 91%). 1H NMR (CDCl3): d=ppm
7.26 (d, 1 H, J ¼ 6.5 Hz), 4.47–4.51 (m, 1 Hz), 4.10, 4.02 (2 quart, 4 H,
J ¼ 7.0 Hz), 3.97 (s, 2 H), 2.22–2.36 (m, 2 Hz), 2.10–2.17 (m, 1 Hz),
1.91–1.99 (m, 2 Hz), 1.18, 1.12 (2 t, 6 H, J ¼ 6.5 Hz).
The compound 7c was obtained according to general procedure of
compound 6 with diethyl N-(2-chloroacetyl)-L-glutamate and isolated
as a white solid (1.5 g, 73%). IR (KBr): v=cmꢄ1 3334, 2104, 1733, 1693;
1H NMR (CDCl3): d=ppm 7.02 (d, 1 H, J ¼ 7.5 Hz), 4.58–4.63 (m,
1 Hz), 4.22, 4.19 (2 quart, 4 Hz), 4.00 (s, 2 H), 2.32–2.46 (m, 2 Hz),
2.18–2.27 (m, 1 Hz), 2.00–2.08 (m, 2 Hz), 1.29, 1.25 (2 t, 6 H, J ¼ 7.0 Hz).
Anal. calcd. for C11H18N4O5: C, 46.15; H, 6.34; N, 19.57. Found: C,
46.21; H, 6.36; N, 19.59.
Synthesis of 8a
A solution of 5-cholesten-3b-tosylate (2.0 g, 3.7 mmol) in freshly distilled
dioxane (24 mL) was allowed to mix with 2-azidoethanol (3.9 g, 12 eq)
and then refluxed for 24 h under an argon atmosphere. After the concen-
tration of the reaction solution, the residue was again dissolved in ethyl
acetate. The organic layer was washed with water, dried over anhydrous

Triazole-Linked Glycoconjugates
839
sodium sulfate, and subsequently filtered and concentrated. The crude
product was purified with column chromatography to finally obtain a
1
white solid 8a (1.0 g, 48%). IR (KBr): v=cmꢄ1 2103; H NMR (CDCl3):
d=ppm 5.36 (d, 1 H, J ¼ 5.0 Hz), 3.67 (t, 2 H, J ¼ 5.0 Hz), 3.37 (t, 2 H,
J ¼ 5.0 Hz), 3.17–3.26 (m, 1 H), 1.00 (s, 3 H), 0.92 (d, 3 H, J ¼ 2.5 Hz),
0.89 (d, 6 H, J ¼ 2.5 Hz), 0.69 (s, 3 H); 13C NMR (CDCl3): d=ppm
140.6, 121.7, 79.7, 66.7, 56.7, 56.1, 51.0, 50.1, 42.3, 39.7, 39.5, 38.9,
37.1, 36.8, 36.2, 35.8, 31.9, 31.8, 28.3, 28.2, 28.0, 24.3, 23.8, 22.8, 22.5,
21.0, 19.3, 18.7, 11.8. Anal. calcd. for C29H49N3O: C, 76.43; H, 10.84;
N, 9.22. Found: C, 76.39; H, 10.90; N, 9.17.
Synthesis of 8b
The compound 8b was obtained according to general procedure of com-
pound 8a with 5-spirosten-3b-tosylate and isolated as a slightly white
1
solid (0.95 g, 57%). IR (KBr): v=cmꢄ1 2103; H NMR (CDCl3): d=ppm
5.33 (d, 1 H, J ¼ 5.0 Hz), 4.39 (quart, 1 H,J ¼ 7.0 Hz), 3.63–3.64 (m, 2
H), 3.43–3.44 (m, 1 H), 3.33–3.38 (m, 3 H), 3.12–3.22 (m, 1 H), 2.39
(dd, 1 H), 2.21 (t, 1 H); 13C NMR (CDCl3): d=ppm 140.7, 121.5, 109.3,
80.8, 79.6, 66.9, 66.8, 62.0, 56.5, 51.0, 50.1, 41.6, 40.2, 39.8, 38.9, 37.1,
36.9, 32.1, 31.8, 30.3, 28.8, 28.3, 20.8, 19.4, 17.1, 16.3, 14.5. Anal. calcd.
for C29H45N3O3: C, 72.01; H, 9.38; N, 8.69. Found: C, 71.97; H, 9.44; N,
8.70.
Synthesis of 9a
The compound 9a was obtained by the reported method.[18,19] To a solu-
tion of 2-propynyl 2,3,4,6-tetra-O-acetyl-b-D-galactopyranoside (3)
(0.2 g, 1.6 mmol) and 1-(azidomethyl)-1H-1,2,4-triazole (6) (0.75 g, 1 eq)
in 20 mL of anhydrous toluene, CuI (0.61 g, 2eq) and N,N-diisopropy-
lethylamine (0.84 mL, 3 eq) were added at room temperature, and the
mixture was stirred for 24 h. At the end of the reaction, as judged by
TLC analysis, the reaction mixture was diluted using 50 mL of water,
the aqueous layer was extracted with ethyl acetate (3 ꢃ 70 mL), and the
combined organic layer was washed with brine solution, dried over anhy-
drous sodium sulfate, and concentrated in vacuo to obtain a crude resi-
due that was purified to obtain the desired 1,4-disubstited 1,2,3-triazole
as a slightly yellow, viscous product (0.72 g, 88%). IR (KBr): v=cmꢄ1
1
2108, 1741; H NMR (CDCl3): d=ppm 8.43 (s, 1 H), 7.86 (s, 1 H), 7.54
(s, 1 H), 6.63 (s, 2 H), 5.33 (d, 1 H, J ¼ 3.5 Hz), 5.16 (dd, 1 H, J ¼ 7.5,
10.5 Hz), 5.05 (d, 1 H, J ¼ 12.5 Hz), 4.98 (dd, 1 H, J ¼ 3.5, 10.5 Hz),

840
X. Zhang, X. Yang, and S. Zhang
4.90 (d, 1 H, J ¼ 12.5 Hz), 4.62 (d, 1 H, J ¼ 7.5 Hz), 4.02–4.08 (m, 2 H),
3.92 (t, 2 H, J ¼ 6.5 Hz), 2.08, 1.95, 1.93, 1.89 (4 s, 12 H); 13C NMR
(CDCl3): d=ppm 170.3, 170.1, 169.9, 169.5, 153.0, 134.3, 144.3, 133.2,
100.5, 72.4, 70.6, 68.5, 67.0, 61.3, 59.1, 58.4, 20.7, 20.6, 20.5. Anal. calcd.
for C20H26N6O10: C, 47.06; H, 5.13; N, 16.46. Found: C, 47.01; H, 5.10;
N, 16.52.
Synthesis of 9b
The compound 9b was obtained according to general procedure of
compound 5a, and isolated as a slightly yellow, viscous product (1.16 g,
92%). IR (KBr): v=cmꢄ1 3147, 2108, 1746, 1668; 1H NMR (CDCl3):
d=ppm 8.43, 7.72 (s, 1 H), 7.27 (t, 2 H), 6.91 (t, 3 H), 5.37 (d, 1 H,
J ¼ 3.5 Hz), 5.26 (s, 2 H), 5.20 (dd, 1 H, J ¼ 8.0, 10.5 Hz), 5.00 (dd, 1
H, J ¼ 3.5, 10.5 Hz), 4.97 (d, 1 H, J ¼ 12.5 Hz), 4.82 (d, 1 H, J ¼ 12.5 Hz),
4.63 (d, 1 H, J ¼ 8.0 Hz), 4.08–4.15 (m, 2 H), 3.91 (t, 2 H, J ¼ 6.5 Hz),
3.76, 3.67, 3.21, 3.15 (4t, 8 H, J ¼ 5.0 Hz), 2.11, 2.02, 1.97, 1.95 (4 s, 12
H). 13C NMR (CDCl3): d=ppm 170.4, 170.2, 170.0, 169.6, 163.3, 150.6,
144.2, 129.3, 124.7, 120.8, 116.7, 100.2, 70.8, 70.7, 68.7, 67.0, 62.7, 61.3,
50.8, 49.5, 49.1, 45.2, 42.2, 20.7, 20.6, 20.5. Anal. calcd. for C29H37N5O11:
C, 55.14; H, 5.90; N, 11.09. Found: C, 55.06; H, 5.97; N, 11.03.
Synthesis of 9c
The compound 9c was obtained according to general procedure of
compound 5a and isolated as a slightly yellow, viscous product (1.08 g,
1
95%). IR (KBr): v =cmꢄ1 3321, 1754, 1698; H NMR (CDCl3): d=ppm
8.43, 7.72 (s, 1 H), 5.30 (d, 1 H, J ¼ 3.5 Hz), 5.09–5.30 (m, 3 H), 4.95
(dd, 1 H, J ¼ 3.5, 10.5 Hz), 4.86 (d, 1 H, J ¼ 12.5 Hz), 4.72 (d, 1 H,
J ¼ 12.5 Hz), 4.58 (d, 1 H, J ¼ 8.0 Hz), 4.03–4.11 (m, 4 H), 3.89–3.94
13
(m, 3 H), 2.05, 1.96, 1.90, 1.87 (4 s, 12 H), 1.17 (t, 3 H, J ¼ 7.0 Hz);
C NMR (CDCl3): d=ppm 170.2, 170.0, 169.8, 169.4, 169.1, 165.4,
144.0, 124.7, 99.8, 70.7, 70.6, 68.5, 67.8, 62.3, 61.2, 52.4, 41.1, 20.7,
19.9, 19.8, 13.6. Anal. calcd. for C23H32N4O1 : C, 48.25; H, 5.63; N,
9.79. Found: C, 48.19; H, 5.87; N, 9.82.
Synthesis of 9d
The compound 9d was obtained according to general procedure of
compound 5a and isolated as a slightly yellow, viscous product (1.24 g,

Triazole-Linked Glycoconjugates
841
93%). IR (KBr): v=cmꢄ1 3350, 2108, 1748, 1699; 1H NMR (CDCl3):
d=ppm 8.43, 7.70 (s, 1 H), 7.24 (s, 1 H), 5.33 (d, 1 H, J ¼ 3.0 Hz), 5.13
(dd, 1 H, J ¼ 8.0, 10.5 Hz), 5.03 (d, 2 H, J ¼ 12.0 Hz), 4.96 (dd, 1 H,
J ¼ 3.5, 10.5 Hz), 4.92 (d, 1 H, J ¼ 12.5 Hz), 4.77 (d, 1 H, J ¼ 12.5 Hz),
4.60 (d, 1 H, J ¼ 8.0 Hz), 4.52 (quart, 1 H, J ¼ 6.0 Hz), 4.04–4.14 (m, 6
H), 3.91 (t, 1 H, J ¼ 6.5 Hz), 2.25–2.38 (m, 2 H), 1.90–2.12 (m, 14 H),
1.17–1.22 (m, 6 H); 13C NMR (CDCl3): d=ppm 172.5, 171.2, 170.3,
170.1, 169.9, 169.5, 165.2, 144.2, 124.8, 99.8, 70.7, 70.6, 68.7, 67.1,
62.3, 61.6, 61.3, 60,6, 52.2, 51.9, 30.1, 26.8, 20.8, 20.5, 20.3, 14.0, 13.9.
Anal. calcd. for C28H40N4O15 : C, 50.00; H, 5.99; N, 8.33. Found: C,
50.10; H, 5.97; N, 8.41.
Synthesis of 9e
The compound 9e was obtained according to general procedure of com-
pound 5a and isolated as a white solid (1.50 g, 89%). IR (KBr): v=cmꢄ1
1748; 1H NMR (CDCl3): d=ppm 8.43, 7.70 (s, 1 H), 5.38 (d, 1 H,
J ¼ 3.5 Hz), 5.30–5.32 (m, 1 H), 5.21 (dd, 1 H, J ¼ 8.0, 10.5 Hz), 4.98
(dd, 1 H, J ¼ 3.5, 10.5 Hz), 4.95 (d, 1 H, J ¼ 12.5 Hz), 4.80 (d, 1 H,
J ¼ 12.5 Hz), 4.64 (d, 1 H, J ¼ 8.0 Hz), 4.45–4.54 (m, 2 H), 4.12–4.19
(m, 2 H), 3.94 (t, 1H, J ¼ 6.5 Hz), 3.78–3.87 (m, 2 H), 3.08–3.15 (m, 1
H), 0.97 (s, 3 H), 0.89 (d, 3 H, J ¼ 3.0 Hz), 0.85 (d, 3 H, J ¼ 2.0 Hz),
0.83 (d, 3 H, J ¼ 2.0 Hz), 0.65 (s, 3 H); 13C NMR (CDCl3): d=ppm
170.3, 170.2, 170.0, 169.4, 143.8, 122.0, 100.1, 79.7, 70.8, 70.7, 68.7,
67.0, 66.2, 62.7, 61,2, 56.7, 56.1, 50.8, 50.1, 42.2, 39.7, 39.4, 38.9, 37.0,
36.7, 36.1, 35.7, 31.8, 28.2, 27.9, 24.2, 23.8, 22.8, 22.6, 21.0, 20.7, 20.6,
20.6, 20.5, 19.3, 18.7, 11.2; ESI MS [M þ H]þm=e: calcd. for
C46H68N3O13, 870.5, found 870.5.
Synthesis of 9f
The compound 9f was obtained according to general procedure of com-
pound 5a and isolated as a white solid (1.48 g, 85%). IR (KBr): v=cmꢄ1
1
1751; H NMR (CDCl3): d=ppm 7.70 (s, 1 H), 5.42 (d, 1 H, J ¼ 3.0 Hz),
), 5.34 (d, 1 H, J ¼ 5.0 Hz), 5.23 (dd, 1 H, J ¼ 8.0, 10.5 Hz), 5.12 (dd, 1 H,
J ¼ 3.5, 10.5 Hz), 4.97 (d, 1 H, J ¼ 12.5 Hz), 4.83 (d, 1 H, J ¼ 12.5 Hz),
4.67 (d, 1 H, J ¼ 8.0 Hz), 4.45–4.46 (m, 2 H), 4.30–4.40 (quart, 1 H,
J ¼ 7.0 Hz), 4.14–4.22 (m, 2 H), 3.96 (t, 1 H, J ¼ 6.5 Hz), 3.81–3.91 (m,
2 H), 3.45–3.51 (m, 1 H), 3.38 (t, 1 H, J ¼ 7.5 Hz), 3.10–3.18 (m, 1 H);
13C NMR (CDCl3): d=ppm 170.2, 170.1, 169.9, 169.3, 143.7, 121.6,
109.1, 100.1, 80.8, 80.7, 70.8, 70.7, 68.7, 67.0, 66.7, 66.1, 62.7, 62.0,

842
X. Zhang, X. Yang, and S. Zhang
61,2, 56.4, 50.7, 49.9, 41.5, 40.1, 39.6, 38.8, 36.9, 36.8, 31.9, 31.7, 31.3,
30.2, 28.7, 28.1, 20.7, 20.6, 20.5, 20.4, 19.2, 17.0, 16.1, 14.4; ESI MS
[M þ H]þ m=e: calcd. for C46H72N3O11 842.5; found 842.6.
ACKNOWLEDGMENTS
This work was supported by the Key Laboratory of Organofluorine
Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy
of Science (No. 04B0021400), the Natural Science Foundation of
Shandong Province (No. Z2006B01), and the Scientific and Technical
Tackle Key Problem Project of Shandong Province (2006GG2203024).
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