Expedient and facile one-pot syntheses of triazole-linked glycoconjugates under microwave irradiation

Article abstract of DOI:10.1055/s-0031-1289728

Effective microwave assisted one-pot syntheses of triazole-O- glycoconjugates and triazolylglycosides involving sequential glycosylation and click chemistry are described. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1289728

PAPER
1079
Expedient and Facile One-Pot Syntheses of Triazole-Linked Glycoconjugates
under Microwave Irradiation
Syntheses
of
T
w
r
iazole-Linked
G
l
a
ycoconjuga
r
te
s
bhanu Sarkar, Samrat Dutta, Asish Kumar Sen*
Chemistry Division, Indian Institute of Chemical Biology, Council of Scientific and Industrial Research, 4, Raja S. C. Mullick Road,
Jadavpur, Kolkata 700 032, India
Fax +91(33)24735197; E-mail: aksen@iicb.res.in
Received 16 July 2011; revised 18 January 2012
zole sugar derivatives were found to have potent
Abstract: Effective microwave assisted one-pot syntheses of triaz-
antitubercular activity in mg/mL level (Figure 1).14 Man-
ole-O-glycoconjugates and triazolylglycosides involving sequential
nosyl triazoles act as FimH antagonists and hence prevent
glycosylation and click chemistry are described.
urinary tract infection.15 Glycosyl triazoles linked to
1,2,4-oxadiazole moiety show potent cell growth inhibi-
Key words: one-pot synthesis, triazole glycoconjugates, multi-
component, glycosylation, click chemistry, microwave irradiation
tion against NCI-H292 (lung carcinoma), HEp-2 (larynx
carcinoma),16 and when linked to a-keto carboxylic acids
were identified as the potent protein tyrosine phosphatase
Glycoconjugates, sugar-linked proteins or lipids through
1B (PTP1B) inhibitors (Figure 1).17 These few examples
O- or N-glycosidic linkage, play a crucial role in various
demonstrate the potency of triazolyl glycosides to be used
life processes.1 Synthetic organic chemistry has provided
as drugs in the near future. Thus, introduction of molecu-
an array of methodologies for preparing glycoconjugates.2
lar diversity in the aglyconic part of triazolyl glycosides
Introduction of unnatural glycosidic linkages, for exam-
may lead to newer ‘lead-molecules’, which may be used
ple, triazolyl glycoconjugates, may provide stability to-
for the treatment of various diseases.
wards hydrolysis of glycosidic bond while retaining the
Normally, ‘click reactions’ are efficient but time-consum-
ing. Microwave heating, at controlled temperature and
pressure may considerably reduce reaction time without
promoting any side reactions. Thus, the synthesis of 1,4-
disubstituted 1,2,3-triazoles under microwave irradiation
may be a suitable alternative.18 It features consecutive
chemical transformation of alkyl halide to alkyl azide and
subsequently to 1,2,3-triazoles, all in one pot.
same geometry and spatial orientations of the natural gly-
coconjugates.3 In addition to this, the modified linkage
may be viable for further chemical transformations.4
The copper(I)-catalyzed Huisgen 1,3-dipolar cycloaddi-
tion reaction between organic azides and terminal alkynes
has been proved to be a versatile synthetic route to 1,4-
disubstituted 1,2,3-triazoles in recent years.5 Because of
the significant biological profile of triazoles, in respect to
anti-HIV,6 anti-allergic,7 antibacterial,8 herbicidal, and
fungicidal activity,9 this click reaction has emerged as an
important topic of organic chemistry.10 Moreover, tria-
zole-linked glycoconjugates, in particular, were found to
have various biological activities. Triazole-O-glycosides
have long been used as fluorescence11 probes and antican-
cer agents.12 1,2,3-Triazole glycosides have been evaluat-
ed for their ability to inhibit the enzymatic activity of
glycosidases; they are also useful as antiviral, antiprolifer-
ative, and antidiabetic agents.13 Quinoline coupled tria-
One-pot sequential multi-component reactions (MCRs),
which combine two or more completely different reac-
tions in a single transformation, provide significant ad-
vantage over conventional stepwise synthesis avoiding
tedious chromatographic purifications. Since carbohy-
drates have found wide applications as biopharmaceuti-
cals or as inhibitors, carbohydrate-based one-pot MCR
producing versatile and diastereomerically pure com-
pounds is one of the most demanding methodology in di-
versity-oriented synthesis program. Due to the inherent
O
HO2C
O
OAc
HO2C
N
N
N
AcO
AcO
OBn
O
O
N
O
BnO
BnO
O
O
O
BnO
BnO
N
N
OAc
OBn
N
N
N
N
BnO
OMe
antituberculosis agent
PTP1B inhibitor
Figure 1 Examples of triazolyl glycosides having potent biological activity
SYNTHESIS 2012, 44, 1079–1089
x
x.
x
x.
2
0
1
2
Advanced online publication: 15.03.2012
DOI: 10.1055/s-0031-1289728; Art ID: N70311SS
© Georg Thieme Verlag Stuttgart · New York

1080
S. Sarkar et al.
PAPER
structural complexity of carbohydrates, the stereoselec-
tive incorporation of azide and/or alkyne in carbohydrate
scaffold unleashes easy access to structurally diverse
compounds. Here, we have revealed an integration of mi-
crowave-assisted glycosylation19 and click chemistry to
synthesize pure diastereomeric triazole-linked glycocon-
jugates in high yield. The glycosides formed through mi-
crowave-accelerated glycosylation of glycosyl donors
underwent subsequent cycloaddition reaction. Copper(II),
which promotes various donors for glycosylation after be-
ing reduced by KI to copper(I), catalyses the cycloaddi-
tion reaction. The reactions were fast and products were
obtained in high yield as pure diastereomers.
Table 1 Effect of Microwave Irradiation on the Formation of 3
Entrya Donor Solvent Microwave
irradiation
Time
Yield (%)b
of 3
1
2
3
2a
2a
2a
DCE
0 W, 25 °C
0 W, 60 °C
100 W, 60 °C
48 h
2.5 h
10 min
42
56
78
Et2O
0 W, 25 °C
0 W, 60 °C
100 W, 60 °C
48 h
48 h
60 min
0
0
0
MeCN 0 W, 25 °C
0 W, 60 °C
48 h
48 h
60 min
0
0
0
100 W, 80 °C
Conventionally, the synthesis of triazole-O-glycoconju-
gates is a two-step process, the first of which involves
Lewis acid promoted glycosylation20 of glycosyl donors
to obtain a- or b-anomers, followed by copper-mediated
azide–alkyne cyclization to form glycoconjugates. This
traditional method includes chromatographic purification
of intermediates and hence the process is tedious and time-
consuming. A recent one-pot approach to accomplish
such glycoconjugates, carbohydrate-furan based hydroxy-
triazoles,10c involved cyclization of TMSN3 and propar-
gylglycoside, where Cu(I) was formed in situ via
disproportionation of Cu(II) and Cu(0). Despite these ad-
vances, there is need to develop new methods to broaden
the scope of this one-pot MCR. Our four-component one-
pot tandem approach (Scheme 1) started with the prepara-
tion of mannose donor 2a–d, which were in turn synthe-
sized from peracylated sugar as reported earlier.20,21
4
5
2b
2b
2b
2c
2c
2c
2d
2d
2d
DCE
Et2O
0 W, 25 °C
100 W, 60 °C
3 h
8 min
62
79
0 W, 25 °C
100 W, 60 °C
1.5 h
10 min
68
73
6
MeCN 0 W, 25 °C
100 W, 80 °C
2 h
10 min
28
70
7
DCE
0 W, 25 °C
100 W, 60 °C
2 h
5 min
60
90
8
Et2O
0 W, 25 °C
100 W, 60 °C
2 h
10 min
62
67
9
MeCN 0 W, 25 °C
100 W, 80 °C
1 h
12 min
60
62
10
11
12
DCE
0 W, 25 °C
100 W, 80 °C
48 h
15 min
0
60
Et2O
0 W, 25 °C
100 W, 60 °C
48 h
15 min
0
5
The terminal alkyne 3 participating in the cycloaddition
reaction was generated in situ through copper(II)-promot-
ed glycosylation of glycosyl donors and propargyl alcohol
at different temperatures and under controlled microwave
heating (Table 1, entries 1–12). It is worthwhile to men-
tion that in conventional procedure, the particular reaction
requires 1–48 hours to complete at room temperature.
MeCN 0 W, 25 °C
100 W, 80 °C
48 h
15 min
0
4
a Reactions were performed using 2a–d (1 equiv), and propargyl alco-
hol (1 equiv) using Cu(OTf)2 (10 mol%) in a microwave vial. Increase
of molar concentration of the catalyst did not produce better result.
b Yield of isolated pure product (some losses during purification were
unavoidable in certain cases).
With the glycosyl chloride 2b, the reaction was found to
proceed smoothly in various solvents under microwave
and showed the best yield in DCE. In the case of 2d, the
reaction was slow and elevation of reaction temperature
did not significantly increase the yield. The thioglycosides
did not participate in the reaction under the same experi-
mental condition. All reactions were carried out using
Cu(OTf)2 (10 mol%) as promoter, while other Cu(II) salts
like CuSO4, CuCl2, and Cu(OAc)2 were not found to pro-
mote the glycosylation.
OAc
OAc
O
AcO
AcO
OAc
OAc
OAc
OAc
O
O
HO
AcO
AcO
KI, TMSN3
R1CH2Br
O
AcO
AcO
N
Cu(OTf)2, DCE
O
N
R
N
2a R = F
2b R = Cl
2c R = OCNHCCl3
2d R = OAc
R1
R1 = alkyl, aryl
3
5a–13a, 50–80%
Scheme 1 Copper-mediated consecutive glycosylation and click chemistry to synthesize triazole-O-glycoconjugates under microwave irra-
diation
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Syntheses of Triazole-Linked Glycoconjugates
1081
Once we standardized the optimal condition for glycosy- 1,2,3-triazoles in good yield, whereas, in the case of ali-
lation, our attention was focused on the consecutive cy- phatic bromides, the yield was found to be poor.
clization, and the results are summarized in Table 2. Entry
Reasonable yields for aliphatic bromides were obtained
3 had been found to show the best yield. Increase in the
only when the temperature was increased from 60 to
amount of catalyst over 10 mol% did not change the over-
85 °C in the cyclization reaction. The copper(I) generated
all yield significantly. However, it is observed that when
from copper(II) by adding KI accelerates the formation of
the amount of catalyst was reduced from 10 mol% the
alkyl azide, and at the same time catalyses the cycloaddi-
tion reactions. The reaction was highly regioselective and
yield of the reaction decreased considerably.
only 1,4-triazoles were obtained.
Table 2 Effect of Microwave Irradiation on the One-Pot Synthesis
of 5a
Next, our efforts were concentrated on the synthesis of tri-
azolylglycosides, as illustrated in Scheme 2. The reaction
of b-D-glucosyl azide to glucosyl triazole with complete
retention of anomeric stereochemistry is known in the lit-
erature.22 The reaction is slow and requires about 18–20
hours to reach completion at room temperature.
Entry Donor
Solvent Microwave
irradiation
Time
Yield
(%)a of 5a
1b
2c
3d
2c
2c
2c
DCE
DCE
DCE
100 W, 60 °C
0 W, 25 °C
5 min
14 h
82
Glycosyl azides are normally formed through the stereo-
selective displacement of a-glycosyl halide with inorgan-
ic azide under homogeneous, phase-transfer or Lewis acid
catalyzed reaction conditions.23 With trichloroacetimidate
2c and 2e as starting materials and copper(II) as promoter,
the glycosyl azides 4c and 4e were formed smoothly un-
der microwave irradiation (100 W, 2 min, 60 °C) using
TMSN3 as acceptor. A participating group at C-2 did not
direct the stereochemistry of anomeric bonds. In the pres-
ence of KI, copper(II) was reduced to copper(I) and glyc-
osyl azide then underwent Huisgen 1,3-dipolar
cycloaddition reaction with alkynes when further exposed
to microwave irradiation (100 W, 3 min, 60 °C). The re-
action sequence when performed without microwave, that
is, at room temperature or at elevated temperature, re-
quired ~20 hours for completion with much lower yield.
The reason may be due to the formation of bulkier triazole
ring compared to glycosyl azide, which is stabilized due
to anomeric effect. On completion of the reaction, all the
volatiles were removed under reduced pressure, diluted
with dichloromethane and washed with saturated aqueous
solution of Na2S2O3 to remove the iodine. On concentra-
tion pure products precipitated out (Table 4, entries 1–9,
11–12); no column chromatography was required.
100 W, 60 °C
100 W, 60 °C
5 min
3 min
72
100 W, 60 °C
100 W, 60 °C
5 min
3 min
88 (80)e
a Yield of isolated pure product (some losses during purification were
unavoidable in certain cases).
b First step was performed in DCE using 2c (1 equiv), and propargyl
alcohol (1 equiv) using Cu(OTf)2 (10 mol%) in microwave vial fol-
lowed by stirring at r.t. with CuSO4 (10 mol%) and sodium ascorbate
in EtOH–H2O (1:1, v/v) with corresponding alkyl halide and NaN3.
c First step as described in method ‘b’, followed by microwave irradi-
ation with metallic Cu, alkyl halide, and TMSN3 as described.
d First step as described in method ‘b’, followed by microwave irradi-
ation with KI, alkyl halide, and TMSN3 as described.
e When performed with 8 mol% Cu(OTf)2.
With this sequential one-pot procedure (Scheme 1), and
its optimal conditions standardized, the scope of the meth-
od was investigated with different halides. The results are
summarized in Table 3. Compound 3 formed through the
activation of trichloroacetimidate donor 2 underwent cy-
clization with the organic azides when irradiated further
(100 W, 3 min, 60 °C) with TMSN3 and corresponding
alkyl halide to produce triazole glycoconjugates (Table 3,
entries 1–12) as pure diastereomers. Benzylic bromides
(Table 3, entries 5–11), as well as other activated halides
such as glycosyl bromide (Table 3, entry 12), gave desired
In conclusion, we have developed a novel Cu(OTf)2/KI-
mediated one-pot synthesis of 1,2,3-triazole bridged gly-
4c X1 = N3
2 = H
OAc
X
Y
Y
OAc
O
1 = OAc
2 = H
N
AcO
AcO
N
N
R2
R2
OAc
14a–15a
OAc
Y1
O
Y1
O
KI
TMSN3
Cu(II)
AcO
AcO
AcO
AcO
OR
X1
X1
Y2
DCE
Y2
X2
X2
OAc
R2
2c X1 = H, X2 = OCNHCCl3
Y1 = OAc, Y2 = H
R2
4c or 4e
KI
O
AcO
AcO
N
2e X1 = OCNHCCl3, X2 = H
N
4e X1 = N3
X
Y
Y
N
OAc
2 = H
Y
1 = H, Y2 = OAc
1 = H
16a–27a
2 = OAc
Scheme 2 Copper-mediated consecutive glycosylation and click chemistry to synthesize triazolylglycosides under microwave irradiation
© Thieme Stuttgart · New York
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1082
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PAPER
Table 3 One-Pot Syntheses of Triazole-O-glycoconjugates under Microwave Irradiation
Entry
Glycoside
Alkyl halide
Triazole-O-glycoconjugatea
Yield (%) a/b
N
N
N
O
O
AcO
AcO
Br
R1
OAc
R2
OAc
R1
R2
1
2
2a
2b
2c
2d
2c
2c
2c
2c
2c
2c
5 (R1 = Me, R2 = H)
5
5a
65 (1:0)
71 (1:0)
88 (1:0)
57 (1:0)
70 (1:0)
68 (1:0)
66 (1:0)
69 (1:0)
71 (1:0)
70 (1:0)
5a
3
5
5a
4
5
5a
5
6 (R1 = H, R2 = H)
7 (R1 = NO2, R2 = H)
8 (R1 = H, R2 = NO2)
9 (R1 = CN, R2 = H)
10 (R1 = F, R2 = H)
11 (R1 = OMe, R2 = H)
6a
6
7a
7
8a
8
9a
9
10a
11a
10
OAc OAc
O
AcO
AcO
O
Br
AcO
AcO
OAc
OAc
N
N
11
2c
61 (1:0)
O
OAc
N
O
OAc
AcO
12
OAc
N
12a
O
O
AcO
N
N
Br
6OH
12
2c
46 (1:0)
AcO
OAc
13
6
OAc
HO
13a
a Reactions were performed using 2a–d (1 equiv), propargyl alcohol (1 equiv), alkyl halide (1 equiv), and Cu(OTf)2 (0.1 equiv) under micro-
wave irradiation (100 W, 60 °C, 5 min) in a microwave vial followed by addition of KI (20 mg) and TMSN3 (1 equiv), with a further irradiation
of 3 min. Anhyd DCE was used as solvent. Products were characterized by spectroscopic and analytical data.
b Isolated yield after column chromatography (some losses during purification were unavoidable in certain cases). a/b-Ratio was confirmed by
1H NMR spectroscopy.
Al plates. The spots were visualized by charring with 10% (v/v)
H2SO4 in EtOH or detected using UV light. Column chromatogra-
phy and flash column chromatography were performed on 60–120
and 230–400 mesh silica gel, respectively. ESI-MS (positive) was
conducted using LC-ESI-Q-TOF Micro Mass spectrometer. The
NMR spectra were taken on a Bruker 300/600 DPX spectrometer
operating at 300/600 MHz for 1H and 75/150 MHz for 13C, respec-
tively, with TMS as an internal standard unless and otherwise stat-
ed, and the chemical shifts are reported in d units. The values of
chemical shifts (d) are given in ppm and coupling constants (J) in
Hz. IR spectra were recorded on a Jasco FTIR (model 410) spectro-
photometer either as neat or on KBr plates.
coconjugates. Microwave irradiation significantly re-
duced reaction time and improved the overall yield.
Cu(OTf)2, used in the reaction protocol, plays dual role in
promoting the glycosylation reaction and later on being
reduced by KI, activates the C≡C bond to undergo ‘click
chemistry’. The methodology may have interesting impli-
cations on the construction of structurally diverse carbo-
hydrate derived heterocycles.
All solvents were dried and purified according to standard methods
prior to use. Analytical TLC was performed on silica gel 60 F254
Synthesis 2012, 44, 1079–1089
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Syntheses of Triazole-Linked Glycoconjugates
1083
Table 4 One-Pot Syntheses of Triazolylglycosides at Room Temperature and Under Microwave Irradiation
Entry
Thioglycoside
Alkyne
Triazolo-glycoconjugatea
Yield (%)b
91 (70)c
N
1
2c
O
N
AcO
AcO
N
OAc
14
OAc
14a
HO
OH
2
2c
86
N
O
N
AcO
N
15
AcO
OAc
OAc
15a
O
O
3
2e
87
N
O
N
AcO
N
16
AcO
OAc
OAc
16a
O
O
4
2e
90
N
O
N
AcO
N
17
AcO
OAc
OAc
17a
O
O
5
2e
90
N
O
N
AcO
N
18
AcO
OAc
OAc
18a
© Thieme Stuttgart · New York
Synthesis 2012, 44, 1079–1089

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S. Sarkar et al.
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Table 4 One-Pot Syntheses of Triazolylglycosides at Room Temperature and Under Microwave Irradiation (continued)
Entry
Thioglycoside
Alkyne
Triazolo-glycoconjugatea
Yield (%)b
O
N
O
6
2e
75
80
79
O
N
AcO
AcO
N
OAc
19
OAc
S
19a
O
O
7
2e
N
O
N
S
AcO
N
20
AcO
OAc
OAc
20a
N
O
O
8
2e
N
O
N
AcO
N
N
21
AcO
OAc
OAc
21a
N
O
Cl
O
Cl
N
Cl
9
2e
80
N
O
N
AcO
AcO
N
Cl
22
OAc
OAc
O
22a
O
O
O
O
O
O
O
O
O
10
2e
91
O
O
N
N
O
N
AcO
AcO
OAc
23
OAc
23a
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Syntheses of Triazole-Linked Glycoconjugates
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Table 4 One-Pot Syntheses of Triazolylglycosides at Room Temperature and Under Microwave Irradiation (continued)
Entry
Thioglycoside
Alkyne
Triazolo-glycoconjugatea
Yield (%)b
O
N
O
11
2e
79
O
N
AcO
AcO
N
24
OAc
OAc
24a
O
N
O
12
2e
69
O
N
AcO
N
25
AcO
OAc
OAc
25a
a Reactions were performed using 2c or 2e (1 equiv), TMSN3 (1 equiv), and Cu(OTf)2 (0.1 equiv) under microwave irradiation (100 W, 60 °C,
2 min) in a microwave vial followed by addition of KI (20 mg) and alkyne (1 equiv), with a further irradiation of 3 min. Anhyd DCE was used
as solvent. Products were characterized by spectroscopic and analytical data.
b Isolated yield. In most cases the product precipitated out (some product may be lost during filtration).
c Isolated yield without the use of microwave; required 20 h at r.t.
Triazole-O-glycoconjugates 5a–13a; General Procedure
HRMS (ESI): m/z calcd for C25H31N3O10 + Na [M + Na]+: 556.1907;
found: 556.1937.
A solution of trichloroacetimidate 2c (0.1 mmol) and propargyl al-
cohol (0.1 mmol) in anhyd DCE (10 mL) was stirred at r.t. with
powdered molecular sieves (4 Å, 20 mg) for 10 min, at the end of
which Cu(OTf)2 (3.6 mg, 0.01 mmol) was added. The mixture was
then exposed to 100 W microwave irradiation maintaining a con-
stant temperature of 60 °C for 5 min, in a microwave vial. When
TLC (eluent: hexane–EtOAc, 3:2) indicated complete consumption
of the starting materials, alkyl halide (0.1 mmol), KI (20 mg),
TMSN3 (11.5 mg, 0.1 mmol), and DCE (5 mL) were added, and the
mixture irradiated further (100 W, 60 °C) for 3 min. The mass was
then filtered, concentrated, diluted with CH2Cl2 (30 mL), and
washed thoroughly with aqueous Na2S2O3 and then purified by col-
umn chromatography (eluent: hexane–EtOAc, 5:1) (Table 3).
6a
Yield: 37 mg (70%); thick glass.
IR (neat): 3472, 3141, 2948, 1748, 1437, 1371, 1228, 1133, 1050
cm–1.
1H NMR (300 MHz, CDCl3): d = 1.98 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.11 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 4.05–4.13
(m, 2 H), 4.25–4.31 (m, 1 H), 4.65 (d, J = 12.3 Hz, 1 H, OCH2Ph),
4.82 (d, J = 12.3 Hz, 1 H, OCH2Ph), 4.93 (s, 1 H), 5.22 (s, 1 H),
5.25–5.30 (m, 2 H), 5.44 (s, 2 H), 7.27–7.50 (m, 6 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.47 (2 × COCH3), 20.56
(COCH3), 20.66 (COCH3), 53.99 (CH2), 60.85 (CH2), 62.09 (CH2),
65.81 (CH), 68.45 (CH), 68.81 (CH), 69.19 (CH), 96.71 (CH),
122.76 (CH), 127.97 (CH), 128.62 (CH), 128.97 (CH), 134.26 (C),
143.64 (CH), 169.50 (COCH3), 169.69 (COCH3), 169.79 (COCH3),
170.47 (COCH3).
5a
Yield: 48 mg (88%); thick glass.
IR (neat): 3626, 3475, 3141, 2941, 2431, 2116, 1747, 1515, 1437,
1371, 1225, 1133 cm–1.
HRMS (ESI): m/z calcd for C24H29N3O10 + Na [M + Na]+: 542.1751;
found: 542.1726.
1H NMR (600 MHz, CDCl3): d = 1.98 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.11 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 2.36 (s, 3
H, CH3), 4.04 (m, 1 H, H-5), 4.07 (m, 1 H, HA-6), 4.28 (m, 1 H, HB-
6), 4.65 (d, J = 12.0 Hz, 1 H, OCH2Ar), 4.81 (d, J = 12.0 Hz, 1 H,
OCH2Ar), 4.93 (s, 1 H, H-1), 5.22 (s, 1 H, H-2), 5.28 (m, 1 H, H-4),
5.29 (m, 1 H, H-3), 5.49 (s, 2 H, NCH2Ar), 7.20–7.28 (m, 4 H, Ar),
7.48 (s, 1 H, Ar).
7a
Yield: 39 mg (68%); thick glass.
IR (neat): 3472, 3142, 2943, 1748, 1605, 1525, 1434, 1353, 1228,
1134, 1049 cm–1.
13C NMR (150 MHz CDCl3): d = 20.60 (COCH3), 20.61 (COCH3),
20.70 (COCH3), 20.80 (COCH3), 53.99 (CH2), 61.04 (CH2), 62.23
(CH2), 65.95 (CH), 68.57 (CH), 68.94 (CH), 69.33 (CH), 96.86
(CH), 122.68 (CH), 128.18 (CH), 129.78 (CH), 131.26 (C), 138.73
(CH), 143.72 (C), 169.63 (COCH3), 169.83 (COCH3), 169.94
(COCH3), 170.61 (COCH3).
1H NMR (300 MHz, CDCl3): d = 1.99 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.11 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 4.05–4.08
(m, 2 H), 4.12–4.13 (m, 1 H), 4.69 (d, J = 12.6 Hz, 1 H, OCH2Ar),
4.86 (d, J = 12.3 Hz, 1 H, OCH2Ar), 4.94 (s, 1 H), 5.21 (s, 1 H),
5.29–5.31 (m, 2 H), 5.67 (s, 2 H), 7.44–8.28 (m, 5 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.61 (2 × COCH3), 20.70
(COCH3), 20.79 (COCH3), 53.11 (CH2), 60.99 (CH2), 62.25 (CH2),
© Thieme Stuttgart · New York
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65.93 (CH), 68.66 (CH), 68.87 (CH), 69.32 (CH), 96.84 (CH),
123.07 (CH), 124.31 (CH), 128.67 (CH), 141.37 (CH), 144.41 (C),
148.04 (CH), 169.62 (COCH3), 169.94 (COCH3), 170.02 (COCH3),
170.64 (COCH3).
HRMS (ESI): m/z calcd for C24H28N4O12 + Na [M + Na]+: 587.1601;
found: 587.1562.
11a
Yield: 39 mg (70%); thick glass.
IR (neat): 3474, 3141, 2948, 2843, 2433, 2116, 1748, 1613, 1515,
1438, 1371, 1228, 1133 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.98 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.11 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 3.81 (s, 3
H, OCH3), 4.06–4.07 (m, 2 H), 4.28 (dd, J = 5.1, 12.3 Hz, 1 H), 4.64
(d, J = 12.3 Hz, OCH2Ar, 1 H), 4.81 (d, J = 12.3 Hz, OCH2Ar, 1 H),
4.93 (s, 1 H), 5.22 (s, 1 H), 5.28–5.30 (m, 2 H), 5.47 (s, 2 H), 6.92
(d, J = 8.7 Hz, 2 H, Ar), 7.25 (d, J = 8.4 Hz, 2 H, Ar), 7.47 (s, 1 H,
Ar).
8a
Yield: 38 mg (66%); thick glass.
IR (neat): 3144, 2950, 1748, 1533, 1437, 1533, 1437, 1361, 1228,
1134, 1049 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.98 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.11 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 4.07–4.12
(m, 2 H), 4.26–4.30 (m, 1 H), 4.69 (d, J = 12.3 Hz, 1 H, OCH2Ar),
4.86 (d, J = 12.3 Hz, 1 H, OCH2Ar), 4.95 (s, 1 H), 5.22 (s, 1 H), 5.30
(s, 2 H), 5.67 (s, 2 H), 7.63–8.26 (m, 5 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.53 (2 × COCH3), 20.63
(COCH3), 20.66 (COCH3), 53.99 (CH2), 60.85 (CH2), 62.09 (CH2),
65.81 (CH), 68.45 (CH), 68.81 (CH), 69.19 (CH), 96.71 (CH),
122.76 (CH), 127.97 (CH), 128.62 (CH), 128.97 (CH), 134.26 (C),
143.64 (CH), 169.50 (COCH3), 169.69 (COCH3), 169.79 (COCH3),
170.47 (COCH3).
13C NMR (75 MHz, CDCl3): d = 20.35 (2 × COCH3), 20.44
(COCH3), 20.54 (COCH3), 53.41 (CH2), 54.98 (CH3), 60.71 (CH2),
61.95 (CH2), 65.66 (CH), 68.31 (CH), 68.73 (CH), 69.06 (CH),
96.61 (CH), 114.19 (2 × CH), 122.53 (CH), 126.14 (C), 129.47
(2 × CH), 143.37 (C), 159.61 (C), 169.42 (COCH3), 169.60
(COCH3), 169.69 (COCH3), 170.37 (COCH3).
HRMS (ESI): m/z calcd for C25H31N3O11 + Na [M + Na]+: 572.1856;
found: 572.1868.
12a
Yield: 47 mg (61%); thick glass.
HRMS (ESI): m/z calcd for C24H28N4O12 + Na [M + Na]+: 587.1601;
found: 587.1601.
IR (neat): 3644, 3149, 2961, 2360, 2118, 1756, 1643, 1435, 1435,
1372, 1229, 1134, 1041 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, COCH3), 1.99 (s, 3
H, COCH3), 2.04 (s, 3 H, COCH3), 2.08 (s, 3 H, COCH3), 2.11 (s, 3
H, COCH3), 2.13 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 4.00–4.19
(m, 4 H), 4.30–4.36 (m, 2 H), 4.69 (d, J = 12.3 Hz, 1 H), 4.86 (d,
J = 12.6 Hz, 1 H), 4.93 (s, 1 H), 5.23–5.47 (m, 6 H), 5.87–5.90 (m,
1 H), 7.86 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 19.93 (COCH3), 20.34 (COCH3),
20.47 (2 × COCH3), 20.50 (2 × COCH3), 20.59 (COCH3), 20.65
(COCH3), 60.53 (CH2), 61.33 (CH2), 62.18 (CH2), 65.81 (CH),
67.48 (CH), 68.55 (CH), 68.83 (CH), 69.15 (CH), 70.16 (CH),
72.34 (CH), 74.93 (CH), 85.54 (CH), 96.63 (CH), 121.43 (CH),
144.04 (C), 168.72(COCH3), 169.17 (COCH3), 169.54 (COCH3),
169.72 (2 × COCH3), 169.75 (COCH3), 170.35 (COCH3), 170.54
(COCH3).
9a
Yield: 38 mg (69%); thick glass.
IR (neat): 3473, 3141, 2948, 2231, 2110, 1747, 1615, 1433, 1371,
1228, 1134 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.99 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.12 (s, 3 H, COCH3), 2.16 (s, 3 H, COCH3), 4.04–4.13
(m, 2 H), 4.29 (dd, J = 5.1, 12.0 Hz, 1 H), 4.68 (d, J = 12.6 Hz, 1 H,
OCH2Ar), 4.86 (d, J = 12.3 Hz, 1 H, OCH2Ar), 4.94 (m, 1 H), 5.21
(s, 1 H), 5.29–5.31 (m, 2 H), 5.62 (s, 2 H), 7.38 (d, J = 8.1 Hz, 1 H,
Ar), 7.58 (s, 1 H, Ar), 7.70 (d, J = 8.4 Hz, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.49 (2 × COCH3), 20.59
(COCH3), 20.68 (COCH3), 53.23 (CH2), 60.77 (CH2), 62.12 (CH2),
65.77 (CH), 68.50 (CH), 68.75 (CH), 69.16 (CH), 96.67 (CH),
112.53 (C), 118.00 (C), 123.06 (CH), 128.35 (2 × CH), 132.75
(2 × CH), 139.49 (C), 144.11 (C), 169.50 (COCH3), 169.82
(COCH3), 169.89 (COCH3), 170.52 (COCH3).
HRMS (ESI): m/z calcd for C31H41N3O19 + Na [M + Na]+: 782.2232;
found: 782.2218.
13a
HRMS (ESI): m/z calcd for C25H28N4O10 + Na [M + Na]+: 567.1703;
Yield: 25 mg (46%); thick glass.
found: 567.1720.
IR (neat): 3462, 3142, 2936, 2865, 2109, 1748, 1439, 1372, 1228,
1135 cm–1.
10a
Yield: 39 mg (71%); thick glass.
1H NMR (300 MHz, CDCl3): d = 1.37–1.6 (m, 8 H), 1.99 (s, 3 H,
COCH3), 2.04 (s, 3 H, COCH3), 2.13 (s, 3 H, COCH3), 2.16 (s, 3 H,
COCH3), 3.63 (t, J = 6.45 Hz, 2 H), 4.05–4.14 (m, 2 H), 4.31 (dd,
J = 12.15, 5.1 Hz, 1 H), 4.36–4.41 (m, 2 H), 4.68 (d, J = 12.3 Hz, 1
H), 4.86 (d, J = 12.3 Hz, 1 H), 4.96 (m, 1 H), 5.25–5.35 (m, 3 H),
7.59 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.52 (2 × COCH3), 20.61
(COCH3), 20.70 (COCH3), 24.90 (CH2), 25.97 (CH2), 29.98 (CH2),
32.11 (CH2), 50.13 (CH2), 60.92 (CH2), 62.15 (CH2), 62.21 (CH2),
65.87 (CH), 68.52 (CH), 68.91 (CH), 69.28 (CH), 96.67 (CH),
122.73 (CH), 143.27 (C), 169.60 (COCH3), 169.90 (COCH3),
169.97 (COCH3), 170.63 (COCH3).
IR (neat): 3473, 3141, 2950, 1749, 1606, 15512, 1436, 1372, 1229,
1134, 1051 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.98 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.11 (s, 3 H, COCH3), 2.15 (s, 3 H, COCH3), 4.06–4.09
(m, 2 H), 4.28 (dd, J = 5.1, 12.3 Hz, 1 H), 4.65 (d, J = 12.3 Hz, 1 H,
OCH2Ar), 4.83 (d, J = 12.3 Hz, 1 H, OCH2Ar), 4.93 (s, 1 H), 5.21
(s, 1 H), 5.22–5.31 (m, 3 H), 5.52 (s, 2 H), 7.01–7.51 (m, 5 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.59 (2 × COCH3), 20.68
(COCH3), 20.77 (COCH3), 53.41 (CH2), 61.04 (CH2), 62.25 (CH2),
65.98 (CH), 68.63 (CH), 68.93 (CH), 69.35 (CH), 96.87 (CH),
115.99 (CH), 116.28 (CH), 122.67 (CH), 129.96 (CH), 130.07
(CH), 130.20 (C), 130.24 (C), 143.97 (C), 169.62 (COCH3), 169.85
(COCH3), 169.95 (COCH3), 170.60 (COCH3).
HRMS (ESI): m/z calcd for C23H35N3O11 + Na [M + Na]+: 552.2169;
found: 552.2186.
HRMS (ESI): m/z calcd for C24H28N3O10 + Na [M + Na]+: 560.1656;
found: 560.1615.
Triazolyl Glycoconjugates 14a–25a; General Procedure
A solution of trichloroacetimidate 2c or 2e (0.1 mmol) and TMSN3
(0.1 mmol) in anhyd DCE (10 mL) was stirred at r.t. with powdered
Synthesis 2012, 44, 1079–1089
© Thieme Stuttgart · New York

PAPER
Syntheses of Triazole-Linked Glycoconjugates
1087
molecular sieves (4 Å, 20 mg) for 10 min, at the end of which
Cu(OTf)2 (0.01 mmol) was added. The mixture was then exposed to
100 W microwave irradiation maintaining a constant temperature of
60 °C for 2 min, in a microwave vial. When TLC (eluent: hexane–
EtOAc, 3:2) indicated complete consumption of the starting materi-
als, KI (20 mg), alkyne (0.1 mmol), and DCE (5 mL) were added
and the mixture irradiated (100 W, 60 °C) further for 3 min. The
mass was then filtered, concentrated, diluted with CH2Cl2 (30 mL)
and washed thoroughly with aqueous Na2S2O3. Pure compounds
precipitated out directly from solution, no column chromatography
was required (Table 4).
HRMS (ESI): m/z calcd for C24H29N3O10 + Na [M + Na]+: 542.1751;
found: 542.1786.
17a
Yield: 52 mg (90%); white solid; mp 113–115 °C.
IR (KBr): 3474, 3074, 1748, 1512, 1455, 1375, 1227, 1095, 1067,
1041 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.87 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.07 (s, 6 H, 2 × COCH3), 3.96–4.00 (m, 1 H), 4.11–
4.15 (m, 2 H), 4.29 (dd, J = 4.8, 12.6 Hz, 1 H), 4.75 (s, 2 H), 5.03
(s, 2 H), 5.21–5.27 (m, 1 H), 5.39–5.45 (m, 2 H), 5.87–5.90 (m, 1
H), 7.42–7.56 (m, 4 H), 7.80 (s, 1 H), 7.84–7.88 (m, 2 H), 8.10 (d,
J = 8.1 Hz, 1 H, Ar).
14a23a
Yield: 44 mg (91%); white solid; mp 177–179 °C.
13C NMR (75 MHz, CDCl3): d = 19.98 (CH3), 20.34 (2 × CH3),
20.48 (CH3), 61.33 (CH2), 63.18 (CH2), 64.46 (CH2), 70.16 (CH),
70.59 (CH), 72.42 (CH), 74.72 (CH), 85.44 (CH), 121.00 (CH),
123.85 (CH), 125.05 (CH), 125.65 (CH), 126.12 (CH), 126.66
(CH), 128.35 (CH), 128.64 (CH), 131.55 (C), 132.97 (C), 145.75
(C), 168.72 (COCH3), 169.20 (COCH3), 169.74 (COCH3), 170.31
(COCH3).
IR (KBr): 3483, 3089, 1749, 1455, 1369, 1262, 1225, 1095, 1068
cm–1.
1H NMR (300 MHz, CDCl3): d = 2.01 (s, 3 H, COCH3), 2.11 (s, 9
H, 3 × COCH3), 3.98–4.03 (m, 1 H), 4.23 (dd, J = 2.1, 12.5 Hz, 1
H), 4.38 (dd, J = 6, 12.6 Hz, 1 H), 5.29–5.42 (m, 2 H), 5.8–5.81 (m,
1 H), 6.19 (s, 1 H), 7.36–7.96 (m, 5 H, Ar), 7.99 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.41 (COCH3), 20.50 (COCH3),
20.59 (COCH3), 20.67 (COCH3), 62.23 (CH2), 65.02 (CH), 68.89
(CH), 70.74 (CH), 75.67 (CH), 84.75 (CH), 118.41 (CH), 125.71
(CH), 125.83 (CH), 128.41 (CH), 128.62 (CH), 128.85 (CH),
130.03 (C), 147.71 (C), 168.94 (COCH3), 169.56 (COCH3), 169.71
(COCH3), 170.48 (COCH3).
HRMS (ESI): m/z calcd for C28H31N3O10 + Na [M + Na]+: 592.1907;
found: 592.1916.
18a
Yield: 57 mg (90%); yellow solid; mp 108–110 °C.
IR (KBr): 3478, 3074, 1749, 1371, 1225, 1097, 1040 cm–1.
HRMS (ESI): m/z calcd for C22H25N3O9 + Na [M + Na]+: 498.1489;
found: 498.1486.
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.06 (s, 3 H, COCH3), 2.07 (s, 3 H, COCH3), 3.98–4.01
(m, 1 H), 4.13 (d, J = 12.0 Hz, 1 H), 4.28 (dd, J = 4.8, 12.5 Hz, 1 H),
5.2–5.26 (m, 1 H), 5.39–5.47 (m, 2 H), 5.58 (s, 2 H), 5.87–5.90 (m,
1 H), 7.45–7.58 (m, 4 H, Ar), 7.79 (s, 1 H), 8.02 (d, J = 8.1 Hz, 1 H,
Ar), 8.35 (d, J = 9.0 Hz, 1 H, Ar), 8.48 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.05 (CH3), 20.40 (CH3), 20.52
(CH3), 20.59 (CH3), 61.39 (CH2), 63.51 (CH2), 64.41 (CH2), 67.50
(CH), 70.25 (CH), 72.49 (CH), 74.81 (CH), 85.54 (CH), 121.14
(CH), 124.12 (2 × C), 124.87 (2 × CH), 126.22 (2 × CH), 128.01
(C), 128.49 (CH), 128.89 (2 × CH), 130.89 (2 × C), 131.26 (2 × C),
145.94 (C), 168.79 (COCH3), 169.25 (COCH3), 169.81 (COCH3),
170.39 (COCH3).
15a
Yield: 51 mg (86%); brown solid; mp 192–194 °C.
IR (KBr): 3492, 3252, 3080, 1752, 1446, 1374, 1230, 1090 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.98 (s, 3 H, COCH3), 2.09 (s, 2
H, 2 × COCH3), 2.12 (s, 3 H, COCH3), 3.99–4.06 (m, 1 H), 4.18 (dd,
J = 2.1, 12.6 Hz, 1 H), 4.35–4.42 (m, 1 H), 5.25–5.43 (m, 2 H),
5.80–5.89 (m, 1 H), 6.20 (s, 1 H), 7.22–7.72 (m, 9 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.40 (COCH3), 20.52 (COCH3),
20.59 (COCH3), 20.64 (COCH3), 62.10 (CH2), 65.22 (CH), 68.74
(CH), 69.04 (CH), 75.52 (CH), 84.25 (CH), 120.19 (CH), 124.84
(CH), 128.31 (CH), 128.61 (CH), 129.01 (CH), 130.03 (CH),
131.58 (CH), 133.64 (CH), 136.98 (C), 139.75 (C), 144.05 (C),
147.78 (C), 163.28 (C), 168.96 (COCH3), 169.61 (COCH3), 169.74
(COCH3), 170.51 (COCH3).
HRMS (ESI): m/z calcd for C32H33N3O10 + Na [M + Na]+: 642.2064;
found: 642.2054.
19a
HRMS (ESI): m/z calcd for C29H29N3O10 + Na[M + Na]+: 602.1751;
Yield: 44 mg (75%); white solid; mp 115–117 °C.
found: 602.1748.
IR (KBr): 3466, 3086, 1752, 1740, 1520, 1458, 1367, 1256, 1235,
1222, 1142, 1042 cm–1.
16a
1H NMR (600 MHz, CDCl3): d = 1.84 (s, 3 H, COCH3), 2.03 (s, 3
H, COCH3), 2.07 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3), 3.33 (d,
J = 7.2 Hz, 2 H), 3.87 (s, 3 H, OCH3), 3.98–4.01 (m, 1 H), 4.14 (dd,
J = 1.8, 12.3 Hz, 1 H), 4.29 (dd, J = 5.4, 12.6 Hz, 1 H), 5.07–5.11
(m, 2 H), 5.22–5.28 (m, 2 H), 5.39–5.46 (m, 2 H), 5.87 (d, J = 9.0
Hz, 1 H), 5.91–5.98 (m, 1 H), 6.7 (dd, J = 1.8, 8.4 Hz, 1 H), 6.73 (d,
J = 1.8 Hz, 1 H), 6.93 (d, J = 7.8 Hz, 1 H), 7.87 (s, 1 H).
13C NMR (150 MHz, CDCl3): d = 20.12 (COCH3), 20.49 (COCH3),
20.52 (COCH3), 20.67 (COCH3), 39.8 (CH2), 55.78 (CH3), 61.50
(CH2), 63.24 (CH2), 67.62 (CH), 70.18 (CH), 72.67 (CH), 75.05
(CH), 85.67 (CH), 112.35 (CH), 114.68 (CH), 115.73 (CH), 120.47
(CH), 121.33 (CH), 134.00 (C), 137.46 (C), 145.24 (C), 145.80 (C),
149.61 (C), 168.82 (COCH3), 169.32 (COCH3), 169.92 (COCH3),
170.51 (COCH3).
Yield: 46 mg (87%); white solid; mp 128–130 °C.
IR (KBr): 3483, 3088, 2360, 1748, 1455, 1368, 1256, 1224, 1097,
1068 cm–1.
1H NMR (600 MHz, CDCl3): d = 1.88 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.07 (s, 3 H, COCH3), 2.08 (s, 3 H, COCH3), 3.99–4.01
(m, 1 H), 4.15 (dd, J = 1.8, 12.6 Hz, 1 H), 4.30 (dd, J = 4.8, 12.6 Hz,
1 H), 4.59 (s, 2 H), 4.69 (s, 2 H), 5.24 (t, J = 9.6 Hz, 1 H), 5.41–5.46
(m, 2 H), 5.87–5.90 (d, J = 9.0 Hz, 1 H), 7.29–7.38 (m, 5 H, Ar),
7.80 (s, 1 H, Ar).
13C NMR (150 MHz, CDCl3): d = 20.17 (COCH3), 20.50 (COCH3),
20.52 (COCH3), 20.67 (COCH3), 60.53 (CH2), 61.50 (CH2), 63.35
(CH2), 67.65 (CH), 70.27 (CH), 72.47 (CH2), 72.60 (CH), 75.07
(CH), 85.72 (CH), 120.88 (CH), 127.84 (CH), 127.96 (CH), 128.45
(CH), 137.60 (C), 146.00 (C), 168.92 (COCH3), 169.34 (COCH3),
169.90 (COCH3), 170.49 (COCH3).
HRMS (ESI): m/z calcd for C27H33N3O11 + Na [M + Na]+: 598.2013;
found: 598.2008.
© Thieme Stuttgart · New York
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1088
20a
S. Sarkar et al.
PAPER
1H NMR (300 MHz, CDCl3): d = 1.31 (s, 3 H, CH3), 1.39 (s, 3 H,
CH3), 1.43 (s, 3 H, CH3), 1.49 (s, 3 H, CH3), 1.88 (s, 3 H, COCH3),
2.03 (s, 3 H, COCH3), 2.07 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3),
3.99–4.33 (m, 8 H), 4.59 (d, J = 3.3 Hz, 1 H), 4.76–4.86 (m, 2 H),
5.20–5.89 (m, 5 H), 7.88 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.08 (CH3), 20.45 (CH3), 20.48
(CH3), 20.62 (CH3), 25.36 (COCH3), 26.15 (COCH3), 26.74
(COCH3), 26.85 (COCH3), 62.48 (CH2), 63.79 (CH2), 67.27 (CH2),
67.61 (CH), 70.22 (CH), 70.36 (CH), 72.55 (CH), 75.15 (CH),
81.03 (CH), 81.77 (CH), 82.52 (CH), 85.73 (CH), 105.21 (CH),
108.99 (C), 111.80 (C), 120.86 (CH), 145.73 (C), 168.85 (COCH3),
169.31 (COCH3), 169.84 (COCH3), 170.41 (COCH3).
Yield: 43 mg (80%); white solid; mp 124–126 °C.
IR (KBr): 3480, 3119, 1755, 1549, 1446, 1417, 1374, 1229, 1155,
1099 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.07 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3), 3.98–4.03
(m, 1 H), 4.14 (dd, J = 1.8, 12.5 Hz, 1 H), 4.30 (dd, J = 5.1, 12.6 Hz,
1 H), 4.59 (s, 2 H), 4.67 (s, 2 H), 5.21–5.27 (m, 1 H), 5.39–5.47 (m,
2 H), 5.86–5.89 (m, 1 H), 7.11 (d, J = 4.8 Hz, 1 H, Ar), 7.27–7.33
(m, 2 H, Ar), 7.89 (s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 19.77 (CH3), 20.15 (CH3), 20.19
(CH3), 20.29 (CH3), 61.23 (CH2), 62.70 (CH2), 66.89 (CH2), 67.34
(CH), 70.05 (CH), 72.23 (CH), 74.45 (CH), 85.17 (CH), 120.94
(CH), 123.11 (CH), 125.77 (CH), 127.18 (CH), 138.44 (C), 145.45
(C), 168.55 (COCH3), 169.08 (COCH3), 169.56 (COCH3), 170.13
(COCH3).
HRMS (ESI): m/z calcd for C29H41N3O15 + Na [M + Na]+: 694.2435;
found: 694.2432.
24a
Yield: 41 mg (79%); yellow solid; mp 148–150 °C.
HRMS (ESI): m/z calcd for C22H27Cl2N3O10S + Na [M + Na]+:
548.1315; found: 548.1277.
IR (KBr): 3483, 3080, 2936, 2853, 1748, 1454, 1368, 1227, 1097,
1039 cm–1.
21a
1H NMR (600 MHz, CDCl3): d = 1.21–1.33 (m, 6 H), 1.74–1.76 (m,
2 H), 1.88 (s, 3 H, COCH3), 1.93–1.95 (m, 2 H), 2.03 (s, 3 H,
COCH3), 2.07 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3), 3.36–3.39
(m, 1 H), 3.98–4.01 (m, 1 H), 4.14 (dd, J = 1.9, 12.5 Hz, 1 H), 4.30
(dd, J = 4.8, 12.5 Hz, 1 H), 4.67 (2 s, 2 H), 5.24 (t, J = 9.6 Hz, 1 H),
5.40–5.48 (m, 2 H), 5.88 (d, J = 9.0 Hz, 1 H), 7.77 (s, 1 H, Ar).
13C NMR (150 MHz, CDCl3): d = 20.18 (COCH3), 20.50 (COCH3),
20.52 (COCH3), 20.67 (COCH3), 24.09 (CH2), 24.10 (CH2), 25.69
(CH2), 32.05 (CH2), 32.15 (CH2), 61.24 (CH2), 61.53 (CH2), 67.67
(CH), 70.21 (CH), 72.70 (CH), 75.02 (CH), 85.64 (CH), 120.57
(CH), 147.05 (C), 168.89 (COCH3), 169.33 (COCH3), 169.91
(COCH3), 170.50 (COCH3).
Yield: 42 mg (79%); white solid; mp 105–107 °C.
IR (KBr): 3472, 3083, 1747, 1600, 1564, 1379, 1366, 1224, 1092,
1033 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.08 (s, 3 H, COCH3), 2.09 (s, 3 H, COCH3), 4.00–4.05
(m, 1 H), 4.13–4.18 (m, 1 H), 4.32 (dd, J = 5.1, 12.6 Hz, 1 H), 4.60
(s, 2 H), 4.74 (s, 2 H), 5.22–5.28 (m, 1 H), 5.40–5.48 (m, 2 H), 5.89–
5.92 (m, 1 H), 7.28–7.30 (m, 2 H, Ar), 7.85 (s, 1 H), 8.59 (d, J = 4.5
Hz, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 19.99 (CH3), 20.35 (CH3), 20.38
(CH3), 20.51 (CH3), 61.38 (CH2), 63.69 (CH2), 67.53 (CH), 70.25
(CH), 70.29 (CH2), 72.37 (CH), 74.94 (CH), 85.59 (CH), 121.01
(CH), 121.76 (2 × CH), 145.19 (C), 146.81 (C), 149.66 (2 × CH),
168.79 (COCH3), 169.22 (COCH3), 169.71 (COCH3), 170.31
(COCH3).
HRMS (ESI): m/z calcd for C23H33N3O10 + Na [M + Na]+: 534.2064;
found: 534.2072.
25a
Yield: 34 mg (69%); yellow solid; mp 118–120 °C.
HRMS (ESI): m/z calcd for C23H28N4O10 + Na [M + Na]+: 543.1703;
found: 543.1714.
IR (KBr): 3482, 3087, 2962, 2874, 1748, 1445, 1371, 1222, 1114,
1042 cm–1.
22a
1H NMR (300 MHz, CDCl3): d = 0.92 (t, J = 7.35 Hz, 3 H, CH3),
1.32–1.44 (m, 2 H, CH3CH2), 1.54–1.64 (m, 2 H, CH3CH2CH2),
1.88 (s, 3 H, COCH3), 2.03 (s, 3 H, COCH3), 2.07 (s, 3 H, COCH3),
2.09 (s, 3 H, COCH3), 3.51 (t, J = 6.6 Hz, 3 H, OCH2CH3), 3.99–
4.03 (m, 1 H), 4.13–4.17 (m, 1 H), 4.30 (dd, J = 5.1, 12.5 Hz, 1 H),
5.21–5.28 (m, 1 H), 5.39–5.49 (m, 2 H), 5.88–5.91 (m, 1 H), 7.78
(s, 1 H, Ar).
13C NMR (75 MHz, CDCl3): d = 13.60 (CH3), 18.95 (CH2), 19.85
(COCH3), 20.21 (COCH3), 20.25 (COCH3), 20.36 (COCH3), 31.35
(CH2), 61.32 (CH2), 63.75 (CH2), 67.43 (CH), 70.05 (CH), 70.20
(CH2), 72.38 (CH), 74.59 (CH), 85.26 (CH), 120.62 (CH), 145.96
(C), 168.61 (COCH3), 169.14 (COCH3), 169.64 (COCH3), 170.23
(COCH3).
Yield: 51 mg (80%); yellowish white solid; mp 140–142 °C.
IR (KBr): 3473, 3136, 3097, 2940, 1749, 1601, 1583, 1487, 1457,
1371, 1224, 1096, 1042 cm–1.
1H NMR (300 MHz, CDCl3): d = 1.88 (s, 3 H, COCH3), 2.04 (s, 3
H, COCH3), 2.08 (s, 3 H, COCH3), 2.10 (s, 3 H, COCH3), 3.99–4.04
(m, 1 H), 4.15 (dd, J = 1.8, 12.5 Hz, 1 H), 4.3 (dd, J = 5.1, 12.5 Hz,
1 H), 4.23–5.30 (m, 1 H), 5.39–5.53 (m, 2 H), 5.66 (s, 2 H), 5.91 (d,
J = 9.0 Hz, 1 H), 7.54–9.02 (m, 5 H, Ar).
13C NMR (75 MHz, CDCl3): d = 20.16 (CH3), 20.50 (2 × CH3),
20.65 (CH3), 61.51 (CH), 67.64 (CH2), 67.72 (CH2), 70.15 (CH),
72.77 (CH), 75.01 (CH), 85.65 (CH), 122.03 (CH), 126.70 (C),
127.00 (C), 127.75 (3 × CH), 133.41 (CH), 143.52 (C), 145.08 (C),
149.60 (C), 150.90 (C), 168.83 (COCH3), 169.31 (COCH3), 169.91
(COCH3), 170.47 (COCH3).
HRMS (ESI): m/z calcd for C21H31N3O10 + Na [M + Na]+: 508.1907;
found: 508.1921.
HRMS (ESI): m/z calcd for C26H26Cl2N4O10 + Na [M + Na]+:
647.0924; found: 647.0927.
Acknowledgment
The authors express their gratitude to Prof. S. Roy, Director, IICB
for continuous encouragements, and the CSIR for providing fel-
lowships to S.S. and S.D. We are indebted to Dr. R. Mukherjee, Mr.
K. Sarkar, and Mr. E. Padmanaban for recording NMR and ESI-
MS.
23a
Yield: 62 mg (91%); white foam.
IR (KBr): 3508, 2990, 2941, 2361, 1756, 1456, 1375, 1227, 1166,
1073 cm–1.
Synthesis 2012, 44, 1079–1089
© Thieme Stuttgart · New York

PAPER
Syntheses of Triazole-Linked Glycoconjugates
1089
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© Thieme Stuttgart · New York
Synthesis 2012, 44, 1079–1089