Synthesis of glycosyl-triazole linked 1,2,4-oxadiazoles

Article abstract of DOI:10.1016/j.carres.2007.07.011

The synthesis of four different types of oxadiazoles containing a terminal acetylenic group is described. Reaction of these oxadiazoles with various azidoglycosides via a copper-catalyzed [3+2] cycloaddition ('click chemistry') afforded the corresponding

Full text of DOI:10.1016/j.carres.2007.07.011

Carbohydrate Research 342 (2007) 2440–2449
Note
Synthesis of glycosyl-triazole linked 1,2,4-oxadiazoles
a,b
c
Janaına V. dos Anjos, Denis Sinou,a, Sebastiao J. de Melo and
*
´
Rajendra M. Srivastavab,*
a
`
´
Laboratoire de Synthese Asymetrique, UMR 5246-ICBMS, CPE Lyon, Universite de Lyon,
´
43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne, France
bDepartamento de Quı´mica Fundamental, Universidade Federal de Pernambuco, Cidade Universita´ria,
50740-540 Recife, PE, Brazil
cDepartamento de Antibio´ticos, Universidade Federal de Pernambuco, Cidade Universita´ria, 50670-901 Recife, PE, Brazil
Received 29 May 2007; received in revised form 2 July 2007; accepted 12 July 2007
Available online 21 July 2007
Abstract—The synthesis of four different types of oxadiazoles containing a terminal acetylenic group is described. Reaction of these
oxadiazoles with various azidoglycosides via a copper-catalyzed [3+2] cycloaddition (‘click chemistry’) afforded the corresponding
glycosyl-triazole linked 1,2,4-oxadiazoles in good yields.
ꢀ 2007 Elsevier Ltd. All rights reserved.
Keywords: Glycosyl azide; 1,2,4-Oxadiazole; [3+2] Cycloaddition; Copper catalyst
1,2,4-Oxadiazoles are a class of important heterocycles.
Many compounds incorporating the 1,2,4-oxadi-
azole ring system showed a large variety of biological
properties.1,2 Moreover, substituted 1,2,4-oxadiazoles
have also been receiving considerable attention as
heterocyclic amide and ester bioisosteres, and have been
implicated in peptide chemistry and in the development
of peptidomimetics.3
Due to these important biological properties, it would
be interesting to incorporate these oxadiazole units in
carbohydrate framework. The reason for this is that
tying up of sugars to other simpler molecules is often
employed to deal with targeting mechanism of action
and/or pharmacology.4 Surprisingly, only a few attempts
have been made in order to synthesize carbohydrate
oxadiazole. Oxadiazoles linked to a glycofuranose,5 gly-
copyranose,3c,6 and also an unsaturated glycopyranose7
skeleton have been described in the literature. In a pro-
gram concerning the incorporation of heterocyclic moie-
ties in carbohydrates, we report in this paper a detailed
account of the preparation of a complex triheterocyclic
system containing a sugar, a triazole, and an oxadiazole
rings in one molecule.
We hypothesized that the oxadiazole framework
could be linked to the glycoside using the copper-cata-
lyzed procedure for the [3+2] cycloaddition (or ‘click
chemistry’)8 between a glycoside containing an anomeric
azide functionality and an oxadiazole bearing a terminal
acetylenic group. Moreover, it has been shown that the
triazole linkage at the anomeric position of carbo-
hydrates is stable under a large variety of acidic or basic
conditions.9
In order to achieve this goal, we prepared 1,2,4-
oxadiazoles bearing a terminal acetylenic group. It was
expected that this functionality could be introduced at
position 5 (compounds 1a,b and 2a,b) or at position 3
(compounds 3a,b and 4) of the oxadiazole framework
(Scheme 1). The chosen substructures are present in
some compounds showing, for example, anti-inflamma-
tory and anti-microbial properties (structures 1–3),10 or
acting as S1P receptor agonist (structures 1, 3, and 4),2c–f
or IL-8 receptor antagonist (structure 1).11
*
Corresponding authors. Fax: +33
4 78898914 (D.S.)/+55 81
The synthesis of these four different types of oxadi-
azoles 1–4 carrying a terminal acetylene function is
21268442 (R.M.S.); e-mail addresses: sinou@univ-lyon1.fr; rms@
ufpe.br
0008-6215/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2007.07.011

J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
2441
N
N
N
ii
i
O
O
O
X
X
X
N
N
N
O
OCH3
OH
5a: X = H
5b: X = Br
6a: X = H
6b: X = Br
1a: X = H
1b: X = Br
N
N
N
iii
O
O
X
X
H
N
OH
O
N
O
7a: X = H
7b: X = Br
2a: X = H
2b: X = Br
NH2
N
iv
v
O
CN
OH
N
N
R
8
9
3a: R = C6H5
3b: R = CH3
N
N
N
vi
vii
O
O
O
HN
H2N
O2N
N
N
N
C6H5
C6H5
C6H5
4
11
10
Scheme 1. Synthesis of acetylenic 1,2,4-oxadiazoles 2, 3, and 4. Reagents and conditions: (i) BBr3, CH2Cl2, reflux, 20 h; (ii) HC„CCH2Br, K2CO3,
DMF, rt, 30 h; (iii) HC„CCH2NH2, N-CH3-morpholine, ClCO2–i-Bu, 24 h, rt; (iv) NH2OH, HCl, NaHCO3, then 4-NC–C6H4C„CH, C2H5OH,
3 days, rt; (v) C6H5CO2H, DCC, CH2Cl2, 3 h, rt, then 110–120 ꢁC; (vi) SnCl2, C2H5OH, reflux; (vii) HC„CCH2Br, K2CO3, DMF, rt, 36 h.
depicted in Scheme 1. 5-Anisyl-1,2,4-oxadiazoles 5a,b
were obtained by condensation of the corresponding
benzamidoximes with p-anisoyl chloride.12 Deprotection
of the aryl methyl ether of compounds 5a,b with boron
tribromide in dichloromethane afforded 5-(4-hydroxy-
phenyl) oxadiazoles 6a and 6b in 53% and 64% yields,
respectively. Condensation of oxadiazoles 6a and 6b
with propargylic bromide gave the corresponding acetyl-
enic oxadiazoles 1a and 1b in 57% and 76% chemical
yields, respectively.
azole 11, whose in situ condensation with propargyl
bromide afforded acetylenic oxadiazole 4 in 63% overall
yield.
The copper(I)-catalyzed 1,3-dipolar cycloaddition of
all terminal alkynes 1–4 was initially performed with
b-glucosyl azide 12 using a 1:1 mixture of dichloro-
methane and water as the solvent in the presence of
Cu(OAc)2 and sodium ascorbate (Table 1).15 O-Proparg-
yloxadiazoles 1a and 1b gave the corresponding cyclo-
adducts 13 and 14 in 80% and 60% yields, respectively,
after 16 h (Table 1, entries 1 and 2). N-Propargylpropane-
amido- and 4-propargylaminophenyl-1,2,4-oxadiazoles
2a, 2b, and 4 also gave the desired b-glycosyl-triazole
linked 1,2,4-oxadiazoles 15, 16, and 19, in 85%, 43%,
and 67% yield, respectively (Table 1, entries 3, 4, and
7). Finally, cycloaddition of ethynylphenyl oxadiazoles
3a and 3b with azidoglucoside 12 afforded the corres-
ponding cycloadducts 17 and 18 in 61% and 80%
chemical yields, respectively.
Among the b-glucosyl 1,2,4-oxadiazoles obtained,
bromooxadiazole 16 is an interesting compound for
further functionalization. For example, the palladium-
catalyzed Suzuki coupling reaction between oxadiazole
14 and phenylboronic acid performed in a water/etha-
nol/toluene mixture afforded the coupled product 20 in
44% chemical yield (Scheme 2).
Reaction of 3-(1,2,4-oxadiazol-5-yl)propionic acids
7a,b13 with isobutyl chloroformate and propargyl amine
afforded acetylenic oxadiazoles 2a and 2b in 78% and
71% yields, respectively.
The synthesis of acetylenic oxadiazoles 3a,b was
performed in a one-pot reaction starting from 4-ethyn-
ylbenzonitrile (8). Treatment of nitrile 8 with hydroxyl-
amine hydrochloride in the presence of sodium
hydrogencarbonate afforded amidoxime 9, whose reac-
tion with benzoic acid in the presence of dicyclohexyl-
carbodiimide, followed by heating at 110 ꢁC, afforded
oxadiazole 3a in an overall yield of 54%. Oxadiazole
3b was obtained in 61% overall yield by heating of ami-
doxime 9 with acetic anhydride.
Finally, reduction of 4-nitrophenyl-5-phenyl-1,2,4-
oxadiazole 1014 with tin chloride gave amino oxadi-

2442
J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
Table 1. Synthesis of glucosyl 1,2,4-oxadiazoles from b-glucosylazide 12 and various acetylenic 1,2,4-oxadiazoles
OAc
OAc
Cu(OAc)2/sodium ascorbate
CH2Cl2/H2O, rt, 20 h
O
O
N
N
AcO
AcO
AcO
AcO
+
R
N
N3
R
OAc
OAc
12
1a
Entry
1
Oxadiazole
Products
Yield (%)
OAc
O
N
N
O
O
AcO
AcO
N
N
N
N
C6H5
O
80
OAc
13
N
C6H5
O N
OAc
OAc
O
N
O
AcO
AcO
N
O
N
N
2
3
4
5
6
7
60
85
43
61
80
67
O
C6H4-p-Br
OAc
N
C6H4-
p-Br
1b
O
N
14
O
O
N
AcO
AcO
N
N
H
N
N
H
N
N
O
O
OAc
O
O
C6H5
N
C6H5
N
O
2a
15
OAc
OAc
O
O
N
AcO
AcO
N
N
N
H
N
N
H
N
N
OAc
C6H4-p-Br
N
C6H4-p-Br
N
2b
O
16
O
AcO
AcO
N
N
N
O
O
N
OAc
C6H5
N
O
3a
C6H5
17
N
N
OAc
OAc
O
N
AcO
AcO
N
N
N
OAc
18
N
CH3
N
O
3b
CH3
O
N
O
AcO
AcO
N
N
N
H
H
N
N
N
C6H5
OAc
N
C6H5
4
O
N
19
Next, we studied the application of different azidogly-
cosides in this copper-catalyzed cycloaddition with
oxadiazole 1a (Table 2). From Table 2, b-azidoglucos-
amine 21, b-azidogalactoside 22, and b-azidocellobio-
side 23 were successfully coupled to the corresponding
b-glycosyl-triazole-linked 1,2,4-oxadiazoles 25, 26, and
27 in 63%, 70%, and 63% yields, respectively. Finally,
reaction of a-azidoglucoside 24 with oxadiazole 1a pro-
vided the corresponding a-D-glucopyranosyl oxadiazole
28 in 67% yield (Tables 3 and 4).
In conclusion, various 1,2,4-oxadiazoles bearing a
terminal acetylenic function in their side-chain have
been successfully cycloadded to azidoglycosides in good
yields via a copper-catalyzed [3+2] reaction. These new
compounds with various chain length as spacer between
the oxadiazole and the glycoside frameworks represent a

J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
2443
OAc
Pd(OAc)2, PPh3, Na2CO3
O
N
AcO
AcO
14 + C6H5B(OH)2
N
Ph
N
O
toluene, EtOH, H2O, 75 °C
OAc
N
O
N
20
Scheme 2. Synthesis of oxadiazole 20.
Table 2. Synthesis of glycosyl 1,2,4-oxadiazoles from various azidoglycosides and oxadiazole 1a
N
N
R
N
Cu(OAc)2/sodium ascorbate
azido carbohydrate
R–N3
O
O
+
O
O
N
N
CH2Cl2/H2O, rt, 20 h
N
N
C6H5
C6H5
1a
Entry
Azidoglycoside
Product
Yield (%)
OAc
OAc
O
O
N
AcO
AcO
AcO
AcO
N
N
N3
O
1
63
70
63
67
NHAc
O
NHAc
N
21
N
25
C6H5
OAc
AcO
AcO
OAc
AcO
AcO
O
N
N
O
N
O
2
3
4
OAc
N3
O
OAc
N
26
N
22
C6H5
OAc
OAc
OAc
OAc
O
OAc
AcO
O
O
AcO
N
AcO
O
N
O
AcO
N
O
AcO
AcO
O
N3
AcO
OAc
AcO
O
OAc
N
27
N
23
C6H5
O
AcO
AcO
OAc
O
AcO
AcO
AcO
N
N
N
AcO
O
N3
O
N
24
28
N
C6H5
set of potentially interesting new compounds, whose
biological studies are currently in progress.
formed on Silica Gel 60 (230–240 mesh, E. Merck).
Optical rotations were recorded using a Perkin–Elmer
241 polarimeter. NMR spectra were recorded with a
Bruker AMX 300 spectrometer and referenced as fol-
1
1. Experimental
lows: H (300 MHz), internal SiMe4 at d = 0.00 ppm,
13C (75 MHz), internal standard at d = 77.23 ppm.
Exact mass measurements of the molecular ions were
obtained on a Finnigan Mat 95 XL spectrometer.
Oxadiazoles 5a,12a 5b,12b 7a,13 7b,13 and 10,14 2,3,4,
6-tetra-O-acetyl-b-D-glucopyranosyl azide (12),16 3,4,
6-tri-O-acetyl-2-acetamido-2-deoxy-b-D-glucopyranosyl
azide (21),15 2,3,4,6-tetra-O-acetyl-b-D-galactopyranosyl
azide (22),17 2,20,3,30,40,6,60-hepta-O-acetyl-b-D-cello-
biosyl azide (23),18 and 2,3,4,6-tetra-O-acetyl-a-D-gluco-
1.1. General methods
All commercially available reagents were used as
received. All reactions were monitored by TLC analysis
(TLC plates GF254 E. Merck). Air- and moisture-sensi-
tive reactions were performed under inert atmosphere.
Melting points were determined on a Buchi apparatus
¨
and are uncorrected. Column chromatography was per-

Table 3. 1H NMR chemical shifts (d in ppm, J in Hz) of compounds 13–20, 25, 26, and 28
Proton
(multiplicity)
13
(Me2SO-d6)
14
(Me2SO-d6)
15
(Me2SO-d6)
16
(Me2SO-d6)
17 (CDCl3)
18 (CDCl3)
19
(Me2SO-d6)
20
(Me2SO-d6)
25
(Me2SO-d6)
26
(Me2SO-d6)
28 (CDCl3)
H-1 (d)
H-2 (dd)
6.39 (J 9.1)
5.69 (J 9.4,
9.2)
6.38 (J 9.2)
5.67 (J 9.4,
9.2)
6.31 (J 9.0)
5.63 (J 9.2,
9.2)
6.31 (J 9.0)
5.63 (J 9.4,
9.0)
5.89 (J 9.0)
5.47 (J 9.2,
9.0)
5.94 (J 8.8)
5.52 (J 9.4,
8.8)
6.32 (J 9.0)
5.65 (J 9.6,
9.4)
6.40 (J 9.0)
5.69 (J 9.2,
9.2)
6.14 (J 10.0)
5.33 (J 10.0,
9.8)
6.31 (J 9.2)
5.62 (J 9.6,
9.2)
6.39 (J 6.0)
5.25–5.33a
H-3 (dd)
H-4 (dd)
H-5 (ddd)
H-6 (dd)
H-60 (dd)
Ac
5.57 (J 9.4,
9.4)
5.19 (J 9.8,
9.6)
4.37 (J 9.8,
5.1, 2.6)
4.08 (J 12.8,
2.6)
4.15 (J 12.8,
5.1)
5.55 (J 9.4,
9.4)
5.19 (J 9.8,
9.6)
4.36–4.39a
5.54 (J 9.4,
9.2)
5.16 (J 9.6,
9.6)
4.36a
5.54 (J 9.4,
9.2)
5.16 (J 9.8,
9.6)
4.36 (J 9.8,
5.3, 3.0)
4.04 (J 12.5,
3.0)
4.12 (J 12.5,
5.3)
5.39 (J 9.2,
9.2)
5.22 (J 9.8,
9.4)
3.98 (J 9.8,
5.1, 1.7)
4.10 (J 12.6,
1.7)
4.28 (J 12.6,
5.1)
5.46 (J 9.4,
9.0)
5.28 (J 9.9,
9.1)
4.05 (J 9.9,
5.1, 2.1)
4.17 (J 12.6,
1.9)
4.35 (J 12.6,
5.1)
5.53 (J 9.6,
9.4)
5.17 (J 9.8,
9.8)
4.37a
5.56 (J 9.4,
9.4)
5.19 (J 9.8,
9.6)
4.38 (J 9.8,
5.3, 1.9)
4.09 (J 12.8,
2.1)
4.16 (J 12.8,
5.5)
5.11 (J 9.8,
9.8)
4.64 (J 10.0,
9.8)
4.25 (J 10.0,
4.9, 2.3)
4.06 (J 12.2,
2.3)
4.16 (J 12.2,
4.9)
1.57, 1.95,
2.00, 2.02
8.50
8.08–8.12a
5.32
5.48 (J 9.6,
3.2)
5.44 (J 3.2,
2.8)
4.60 (J 7.2,
4.9, 2.8)
4.03 (J 11.7,
7.2)
4.14 (J 11.7,
4.9)
6.27 (J 9.9,
9.4)
5.25–5.33a
4.40b (J
10.0)
4.04b (J
12.6)
4.27 (J 12.6,
3.6)
1.83, 2.04,
2.06, 2.07
7.76
4.08 (J 12.8,
3.0)
4.15 (J 12.8,
5.6)
1.76, 1.96,
2.00, 2.02
8.61
4.05 (J 12.4,
2.2)
4.12 (J 12.4,
5.5)
1.79, 1.96,
1.99, 2.03
8.21
4.03b (J
11.7)
4.12 (J 11.7,
5.1)
1.74, 1.95,
1.98, 2.02
8.31
1.77, 1.97,
2.00, 2.03
8.62
1.79, 1.96,
1.99, 2.03
8.20
1.84, 1.98,
2.02, 2.03
8.04
1.90, 2.05,
2.09, 2.10
8.09
1.78, 1.97,
2.00, 2.03
8.62
1.79, 1.95,
1.99, 2.20
8.57
@CHN– (s)
NH (t)
CH2O (s)
CH2N (d)
Other CH2
(t)
8.60 (J 5.5)
8.59 (J 5.5)
6.90 (J 4.5)
5.34
5.33
5.34
5.33
5.36
4.32 (J 5.5)
2.75 (J 7.2)
3.21 (J 7.2)
7.53–7.59
(m, 3H)
4.31 (J 5.5)
2.73 (J 7.1)
3.21 (J 7.1)
7.77 (br d,
2H, J 8.6)
7.92 (br d,
2H, J 8.6)
4.40 (J 4.5)
2.68 (s)c
Harom
7.30 (d, 2H,
J 8.9)
7.60–7.62
(m, 3H)
7.29 (d, 2H,
J 8.9)
7.81 (d, 2H,
J 8.5)
7.48–7.59
(m, 3H)
7.93 (d, 2H,
J 8.1)
7.96 (d, 2H,
J 8.3)
8.14 (d, 2H,
J 8.5)
6.75 (br d,
2H, J 8.5)
7.63–7.72
(m, 3H)
7.30 (d, 2H,
J 8.9)
7.41–7.55
(m, 3H)
7.31 (d, 2H,
J 8.9)
7.58–7.62
(m, 3H)
7.32 (d, 2H,
J 8.9)
7.57–7.62
(m, 3H)
7.15 (d, 2H,
J 7.9)
7.49–7.52
(m, 3H)
7.97–8.00
(m, 2H)
8.08–8.11
(m, 2H)
8.15 (d, 2H,
J 8.9)
8.02 (dd,
2H, J 8.5)
8.13 (d, 2H,
J 8.9)
8.16–8.18
(m, 2H)
8.19 (d, 2H,
J 8.1)
7.80 (d, 2H,
J 8.7)
8.15 (br d,
2H, J 8.3)
7.77 (d, 2H,
J 7.7)
7.91 (d, 2H,
J 8.3)
8.08–8.12
(m, 3H)
8.15 (d, 2H,
J 8.9)
8.09 (br d,
2H, J 7.9)
8.15 (br d,
2H, J 8.9)
8.15–8.20
(m, 4H)
8.16 (d, 2H,
J 8.9)
8.18 (d, 2H,
J 8.3)
a m.
b br d.
c CH3.

J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
2445
Table 4. 13C NMR chemical shifts (d in ppm, CDCl3) of compounds 13–20, 25, 26, and 28
Compound
13
14
15
16
17
18
19
20
86.3
25
85.1
26
86.6
28
81.9
C-1
86.2
86.2
86.0
86.0
86.3
86.3
86.1
C-2
C-3
70.7
72.9
70.7
72.9
70.8
73.0
70.8
72.9
70.7
73.1
70.7
73.0
70.6
73.0
70.7
72.9
52.4
72.8
68.3
71.0
70.2
70.7
C-4
68.0
68.1
68.0
68.0
68.4
68.1
68.1
68.1
68.3
67.3
68.3
C-5
75.6
75.5
75.4
75.4
75.6
75.6
75.5
75.6
73.8
74.4
71.7
C-6
62.3
62.3
61.9
61.8
62.0
61.9
61.9
62.3
62.1
62.3
62.3
@CHNtriaz
@CNtriaz
Coxadiaz
115.7
144.6
169.2
175.8
117.9
121.8
127.4
127.9
129.2
130.5
131.5
161.9
115.7
144.5
168.4
175.9
117.6
121.8
125.9
126.4
129.3
130.5
132.4
162.0
121.6
145.7
168.5
179.3
126.1
126.4
127.1
127.7
129.2
131.5
168.6
121.5
145.6
169.1
179.5
125.8
126.1
126.3
129.2
132.5
169.1
118.9
148.1
168.4
177.5
124.7
126.7
127.4
128.5
128.6
129.5
133.0
133.2
169.0
20.6
118.8
148.0
167.1
177.5
126.6
127.2
128.3
132.9
168.4
116.6
146.7
169.2
175.5
120.6
124.9
128.5
129.4
132.9
150.1
115.7
144.2
169.3
175.8
117.9
126.3
127.5
127.9
128.3
129.3
130.5
140.6
162.0
20.5
116.1
142.6
168.4
175.5
116.4
124.2
126.6
127.4
129.6
130.3
131.9
162.1
115.7
144.4
169.1
175.7
117.8
121.9
127.4
127.8
129.2
130.4
131.5
161.9
115.6
143.5
169.2
175.8
118.0
125.6
127.4
127.9
129.2
130.5
131.5
161.9
Carom
CH3CO
20.5
20.8
20.9
20.5
20.8
20.9
20.5
20.9a
21.0
20.5
20.8
20.9
20.6a
20.9
21.1
20.5
20.8
20.9
20.6
20.7
20.8
20.6
20.9
21.0a
20.6
20.9
21.0a
21.0
21.1
20.8
20.9
21.1
21.0
21.0
26.0
21.1
21.1
22.6
CH3CO
169.3
169.7
170.3
170.8
61.9
169.3
169.7
170.2
170.8
61.9
169.2
169.7
170.3
170.9
22.7
169.7
170.3
170.8
170.9
22.6
169.4
169.7
170.3
170.8
169.4
169.7
169.3
170.8
12.8b
169.3
169.8
170.3
170.9
39.7
169.4
169.7
170.3
170.8
61.9
168.7
169.8
169.9
170.0
61.6
169.4
170.1
170.3
170.7
61.6
169.2
170.0
170.5
170.8
61.6
Other CH2
32.3
32.3
35.3
35.2
a Two carbon signals.
b Methyl group.
pyranosyl azide (24),19 were prepared according to
known literature procedures.
3H, Harom), 8.11–8.17 (m, 4H, Harom); 13C NMR
(CDCl3): d 116.5, 127.3, 127.9, 129.3, 130.6, 155.1,
169.2, 176.0; HREIMS: m/z 238.0741. Calcd for
C14H10N2O2 [M]+: 238.0742.
1.2. Synthesis of 3-aryl-5-(4-hydroxyphenyl)-1,2,4-
oxadiazoles 6a,b
1.2.2.
3-(4-Bromophenyl)-5-(4-hydroxyphenyl)-1,2,4-
A 1 M soln of BBr3 in CH2Cl2 (20 mL, 20 mmol) was
added slowly at ꢀ78 ꢁC to a soln of oxadiazole 5
(6.6 mmol) in CH2Cl2 (30 mL). The reaction mixture
was allowed to warm at rt, and then refluxed for 20 h.
The reaction mixture was treated with water (20 mL)
to hydrolyze the excess of BBr3. After separation of
the organic phase, the aq phase was extracted with
CH2Cl2 (3 · 100 mL). The combined organic phases
were washed with satd aq NaHCO3, then brine, and fi-
nally dried over Na2SO4. Removal of the solvent under
diminished pressure gave a residue that was purified by
column chromatography over silica gel to give the corre-
sponding 5-hydroxyphenyl oxadiazole 6.
oxadiazole (6b). Prepared from 5b (2.18 g); 1.34 g
(64%); colorless solid; mp 216 ꢁC; Rf 0.63 (4:1
1
CH2Cl2–EtOAc); H NMR (CDCl3): d 5.39 (br s, 1H,
OH), 6.99 (d, 2H, J 8.3 Hz, Harom), 7.65 (d, 2H, J
8.3 Hz, Harom), 8.03 (d, 2H, J 8.3 Hz, Harom), 8.12 (d,
2H, J 8.5 Hz, Harom); 13C NMR (DMSO-d6): d 114.3,
116.5, 125.3, 125.9, 129.2, 130.4, 132.4, 162.4, 167.5,
175.9; HREIMS: m/z 315.9857. Calcd for C14H9BrN2O2
[M]+: 315.9847.
1.3. Synthesis of oxadiazoles 1a,b
8-(4-Hydroxyphenyl)oxadiazole
6
(1.26 mmol) and
K2CO3 (260 mg, 1.9 mmol) were suspended in anhyd
DMF (8 mL). Propargyl bromide (220 mg, 1.9 mmol,
80% sol in toluene) was slowly added under a N2 atmo-
sphere, and the reaction mixture was stirred for 30 h at
rt. Cold water (20 mL) was added to the contents, and
the mixture thus obtained was extracted with ethyl ace-
1.2.1.
3-Phenyl-5-(4-hydroxyphenyl)-1,2,4-oxadiazole
(6a). Prepared from 5a (1.67 g); 0.832 g (53%); color-
less solid; mp 161 ꢁC, lit.20 169–171 ꢁC; Rf 0.59 (4:1
1
CH2Cl2–EtOAc); H NMR (CDCl3): d 6.07 (br s, 1H,
OH), 6.98 (br d, 2H, J 8.9 Hz, Harom), 7.50–7.53 (m,

2446
J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
tate (3 · 20 mL). The combined organic layers were
washed with satd aq NaHCO3, brine, and finally dried
(Na2SO4). The solvent was removed under diminished
pressure, and the residue was purified by column chro-
matography on silica gel to afford the corresponding
acetylenic oxadiazoles 1.
d 22.7, 29.8, 32.4, 72.2, 79.7, 127.1, 127.8, 129.2, 131.6,
168.6, 170.4, 179.1; HREIMS: m/z 255.1023. Calcd for
C14H13N3O2 [M]+: 255.1009.
1.4.2. 3-[3-(4-Bromophenyl)-1,2,4-oxadiazol-5-yl]-N-(prop-
2-yn-1-yl)propanamide (2b). Prepared from 7b (273
mg); 218 mg (71%); colorless solid; mp 170 ꢁC; Rf 0.52
(4:1 CH2Cl2–EtOAc); 1H NMR (CDCl3): d 2.24 (t,
1H, J 2.5 Hz, C„CH), 2.81 (t, 2H, J 7.2 Hz, CH2),
3.31 (t, 2H, J 7.2 Hz, CH2), 4.08 (dd, 2H, J 5.2,
2.5 Hz, NCH2), 5.94 (br s, 1H, NH), 7.62 (br d, 2H, J
8.5 Hz, Harom), 7.93 (br d, 2H, J 8.5 Hz, Harom); 13C
NMR (DMSO-d6) 21.1, 27.2, 30.0, 72.3, 80.3, 124.3,
124.8, 128.2, 131.6, 166.0, 169.0, 179.5; HREIMS: m/z
333.0122. Calcd for C14H12BrN3O2 [M]+: 333.0113.
1.3.1.
3-Phenyl-5-[4-(prop-2-yn-1-yloxy)phenyl]-1,2,4-
oxadiazole (1a). Prepared from 6a (300 mg); 198 mg
(57%); colorless solid; mp 107 ꢁC; Rf 0.82 (3:2 petroleum
ether–EtOAc); 1H NMR (CDCl3): d 2.58 (t, 1H, J
2.4 Hz, C„CH), 4.79 (d, 2H, J 2.4 Hz, CH2), 7.13 (d,
2H, J 8.9 Hz, Harom), 7.49–7.52 (m, 3H, Harom), 8.15–
8.20 (m, 4H, Harom); 13C NMR (CDCl3): d 56.3, 76.7,
78.1, 115.8, 118.1, 127.9, 129.2, 130.4, 131.5, 161.4,
169.2, 175.9; HREIMS: m/z calcd for C17H12N2O2
[M]+: 276.0899; found: 276.0901.
1.5. 4-Ethynylbenzamidoxime (9)
1.3.2. 3-(4-Bromophenyl)-5-[4-(prop-2-yn-1-yloxy)phen-
yl]-1,2,4-oxadiazole (1b). Prepared from 6b (399 mg);
340 mg (76%); colorless solid; mp 153 ꢁC; Rf 0.85 (3:2
To a soln of hydroxylamine hydrochloride (540 mg,
7.8 mmol) and sodium hydrogencarbonate (655 mg,
7.8 mmol) in water (20 mL) was added a soln of 4-
ethynylbenzonitrile (8) (500 mg, 3.9 mmol) in ethanol
(20 mL). After being stirred for 3 days at rt, the solvent
was removed under diminished pressure and the residue
was extracted with ethyl acetate (3 · 20 mL). Removal
of the solvent under diminished pressure gave a solid
that was crystallized in CH2Cl2 to give 4-ethynyl-
benzamidoxime 9 (540 mg, 93%) as a colorless solid:
mp 132–133 ꢁC (CH2Cl2); Rf 0.35 (2:1 petroleum
1
petroleum ether–EtOAc); H NMR (CDCl3): d 2.50 (t,
1H, J 2.4 Hz, C„CH), 4.79 (d, 2H, J 2.4 Hz, CH2),
7.04 (d, 2H, J 8.9 Hz, Harom), 7.56 (br d, 2H, J 8.7 Hz,
H
arom), 7.95 (br d, 2H, J 8.7 Hz, Harom), 8.07 (br d,
2H, J 8.9 Hz, Harom); 13C NMR (CDCl3): d 56.3, 76.7,
78.0, 115.8, 117.9, 126.0, 126.4, 129.4, 130.4, 132.5,
161.5, 168.5, 176.0; HREIMS: m/z 353.9991. Calcd for
C17H11BrN2O2 [M]+: 354.0004.
1
ether–EtOAc); H NMR (CDCl3): d 1.63 (s, 1H, OH),
1.4. Synthesis of oxadiazoles 2
3.16 (s, 1H, C„CH), 4.86 (br s, 2H, NH2), 7.52 (br d,
2H, J 7.8 Hz, Harom), 7.60 (br d, 2H, J 7.8 Hz, Harom).
Anal. Calcd for C9H8N2O: C, 67.49; H, 5.03; N, 17.49.
Found: C, 67.15; H, 4.86; N, 17.67.
To a soln of oxadiazole 7 (0.92 mmol) in anhyd THF
(10 mL) maintained at ꢀ25 ꢁC and under a nitrogen
atmosphere were successfully added N-methyl-morphol-
ine (93 mg, 0.92 mmol), isobutyl chloroformate (130 mg,
0.92 mmol), and propargylamine (60 mg, 1.0 mmol).
After being stirred at rt for 24 h, the solvent was
removed under diminished pressure, water (10 mL)
was added, and the pH of the mixture was adjusted
between 1 and 2 with aq 1 N HCl. The aq soln was
extracted with EtOAc (3 · 20 mL), the combined organ-
ic phases were washed with satd aq NaHCO3
(3 · 10 mL), and brine. Removal of the solvent under
diminished pressure afforded oxadiazole 2, which was
recrystallized from a CH2Cl2–hexane mixture.
1.6. 3-(4-Ethynylphenyl)-5-phenyl-1,2,4-oxadiazole (3a)
To
a soln of 4-ethynylbenzamidoxime 9 (0.5 g,
3.47 mmol) in anhyd CH2Cl2 (30 mL) was added
benzoic acid (0.85 g, 6.94 mmol), followed by DCC
(1.43 g, 6.94 mmol), at rt and under a nitrogen
atmosphere. After being stirred for 3 h, the solid was
filtered off, the solvent was removed under diminished
pressure, and the residue was submitted to the cyclo-
dehydration reaction at 110–120 ꢁC for 4 h. The result-
ing mixture was submitted to column chromatography
on silica gel (7:3 hexane–EtOAc) to give oxadiazole
3a (461 mg, 54%) as a colorless solid: mp 99–100 ꢁC;
1.4.1. 3-(3-Phenyl-1,2,4-oxadiazol-5-yl)-N-(prop-2-yn-1-
yl)propanamide (2a). Prepared from 7a (200 mg);
183 mg (78%); colorless solid; mp 98 ꢁC; Rf 0.48 (4:1
1
Rf 0.6 (7:3 hexane–EtOAc); H NMR (CDCl3): d 3.21
(s, 1H, C„CH), 7.51–7.63 (m, 5H, Harom), 8.13
(br d, 2H, J 6.7 Hz, Harom), 8.21 (br d, 2H, J 6.7 Hz,
1
CH2Cl2–EtOAc); H NMR (CDCl3): d 2.23 (t, 1H, J
2.5 Hz, C„CH), 2.82 (t, 2H, J 7.2 Hz, CH2), 3.32 (t,
2H, J 7.2 Hz, CH2), 4.09 (dd, 2H, J 5.2, 2.5 Hz,
NCH2), 5.95 (br s, 1H, NH), 7.44–7.51 (m, 3H, Harom),
8.05 (dd, 2H, J 7.7, 2.0 Hz, Harom); 13C NMR (CDCl3):
H
arom); 13C NMR (CDCl3): d 79.7, 83.5, 124.5, 125.3,
127.5, 127.8, 128.6, 129.5, 133.0, 133.2, 168.7, 176.3;
HREIMS: m/z 246.0805. Calcd for C16H10N2O [M]+:
246.7930.

J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
2447
1.7. 3-(4-Ethynylphenyl)-5-methyl-1,2,4-oxadiazole (3b)
mixture of 4-ethynylbenzamidoxime (9) (0.5 g,
and water (4 mL). To this soln was added a mixture of
Cu(OAc)2 (36 mg, 0.2 mmol) and sodium ascorbate
(79 mg, 0.4 mmol). The resulting mixture was stirred un-
der nitrogen at rt until TLC analysis indicated complete
consumption of the product. The mixture was diluted
with CH2Cl2 (5 mL) and water (5 mL). The organic
layer was separated, and the aq phase was extracted
again with CH2Cl2 (5 mL). The combined organic layers
were dried over Na2SO4. Removal of the solvent under
diminished pressure gave a residue that was purified
by column chromatography on silica using the indicated
eluent to give the corresponding carbohydrate–triazole
linked 1,2,4-oxadiazole.
A
3.13 mmol) and Ac2O (10 mL) was heated at reflux tem-
perature for 4 h. The mixture was cooled to rt, and neu-
tralized with satd aq NaOH until pH 7.0. The organic
product was extracted with EtOAc (3 · 5 mL). Removal
of the solvent under diminished pressure gave a residue
that was purified by column chromatography on silica
gel (3:2 petroleum ether–EtOAc) to give oxadiazole 3b
(350 mg, 61%) as a colorless solid: mp 71 ꢁC; Rf 0.65
(3:2 petroleum ether–EtOAc); 1H NMR (CDCl3): d
2.64 (s, 3H, CH3), 3.21 (s, 1H, C„CH), 7.58 (br d,
2H, J 8.5 Hz, Harom), 8.02 (br d, 2H, J 8.7 Hz, Harom);
13C NMR (CDCl3): d 12.7, 79.7, 83.4, 125.3, 127.4,
127.6, 132.9, 168.2, 177.1; HREIMS: m/z 184.0636.
Calcd for C11H8N2O [M]+: 184.0636.
1.9.1. 5-(4-{[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranos-
yl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-3-phenyl-1,2,4-
oxadiazole (13). Prepared from 12 (373 mg) and 1a
(303.6 mg); 519.7 mg (80%); colorless solid; mp 173 ꢁC;
20
1.8. [4-(5-Phenyl-1,2,4-oxadiazol-3-yl)phenyl](prop-2-
yn-1-yl)amine (4)
Rf 0.25 (3:2 petroleum ether–EtOAc); ½aꢁD ꢀ31.5 (c
1.0, CH2Cl2); HRESIMS: m/z 672.1922. Calcd for
C31H31N5O11Na [M+Na]+: 672.1918. Anal. Calcd for
C31H31N5O11: C, 57.32; H, 4.81. Found: C, 57.22; H,
4.78.
A soln of nitrooxadiazole 10 (1.1 g, 4.1 mmol) in EtOH
(50 mL) was refluxed in the presence of SnCl2 (3.1 g,
16.4 mmol). After total consumption of the starting
material as shown by TLC, the mixture was basified
with satd aq NaHCO3 until pH 8.0, and extracted with
ethyl acetate (3 · 100 mL). Removal of the solvent
under diminished pressure furnished crude 4-aminophen-
yl-5-phenyl-1,2,4-oxadiazole 11, which was used in the
next step without further purification. To a suspension
of aminooxadiazole 11 (400 mg, 1.7 mmol) and potas-
sium carbonate (470 mg, 3.4 mmol) in anhyd DMF
(10 mL) was added slowly propargyl bromide (400 mg,
3.4 mmol) in toluene (80% soln). After being stirred
for 36 h at rt, water (10 mL) was added, and the organic
product was extracted with ethyl acetate (3 · 20 mL).
The combined organic layers were dried (Na2SO4). Sol-
vent removal under diminished pressure gave a residue
that was purified by chromatography on silica gel using
petroleum ether–EtOAc (3:2) as the eluent to afford
oxadiazole 4 (320 mg, 68%) as a yellow solid: mp
117 ꢁC; Rf 0.71 (3:2 petroleum ether–EtOAc); 1H
NMR (CDCl3): d 2.26 (t, 1H, J 2.4 Hz, C„CH), 3.99
(d, 2H, J 2.4 Hz, CH2), 4.27 (br s, 1H, NH), 6.76 (br
d, 2H, J 8.9 Hz, Harom), 7.26–7.61 (m, 3H, Harom),
8.02 (br d, 2H, J 8.9 Hz, Harom), 8.20 (br d, 2H, J
7.9 Hz, Harom); 13C NMR (CDCl3): d 33.7, 72.1, 80.7,
113.5, 117.1, 124.9, 128.5, 129.3, 129.4, 132.9, 149.6,
169.3, 175.5; HREIMS: m/z 275.1062. Calcd for
C17H13N3O [M]+: 275.1059.
1.9.2. 5-(4-{[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranos-
yl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-3-(4-bromo-
phenyl)-1,2,4-oxadiazole (14). Prepared from 12
(373 mg) and 1b (390 mg); 343.5 mg (60%); colorless
solid; mp 227 ꢁC; Rf 0.34 (3:2 petroleum ether–EtOAc);
20
½aꢁD ꢀ29 (c 1.0, CH2Cl2); HRESIMS m/z 729.1118.
Calcd for C31H31BrN5O11 [M+H]+: 729.1132. Anal.
Calcd for C31H30BrN5O11: C, 51.11; H, 4.15. Found:
C, 50.90; H, 4.21.
1.9.3. N-{[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
1H-1,2,3-triazol-4-yl]methyl}-3-(3-phenyl-1,2,4-oxadiazol-
5-yl)propanamide (15). Prepared from 12 (373 mg) and
2a (280.5 mg); 534 mg (85%); colorless solid; mp 153 ꢁC;
20
Rf 0.46 (EtOAc); ½aꢁD ꢀ19.2 (c 1.0, CH2Cl2); HRESIMS
m/z 651.2029. Calcd for C28H32N6O11Na [M+Na]+:
651.2027.
1.9.4. N-{[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
1H-1,2,3-triazol-4-yl]methyl}-3-[3-(4-bromophenyl)-1,2,4-
oxadiazol-5-yl]propanamide (16). Prepared from 12
(373 mg) and 2b (367 mg); 237 mg (43%); colorless solid;
20
mp 82 ꢁC; Rf 0.41 (EtOAc); ½aꢁD ꢀ18.0 (c 1.0, CH2Cl2);
HRESIMS: m/z 729.1118. Calcd for C28H31BrN6O11Na
[M+Na]+: 729.1131.
1.9. General procedure for the preparation of carbo-
hydrate–triazole linked oxadiazole derivatives
1.9.5. 3-{4-[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranos-
yl)-1H-1,2,3-triazol-4-yl]phenyl}-5-phenyl-1,2,4-oxadiaz-
ole (17). Prepared from 12 (373 mg) and 3a (270.6 mg);
378 mg (61%); colorless solid; mp 232 ꢁC; Rf 0.41 (3:2
The azidosugar (1 mmol) and acetylenic oxadiazole
(1.1 mmol) were suspended in 1:1 mixture of CH2Cl2
20
petroleum ether–EtOAc); ½aꢁD ꢀ60.5 (c 1.0, CH2Cl2);

2448
J. V. dos Anjos et al. / Carbohydrate Research 342 (2007) 2440–2449
HRESIMS: m/z 642.1812. Calcd for C30H29N5O10Na
131.5, 144.5, 162.0, 169.2, 169.4, 169.5, 169.7, 169.9,
170.6, 170.8, 175.8. Anal. Calcd for C41H47N5O19: C,
55.07; H, 5.01. Found: C, 54.76; H, 5.06.
[M+Na]+: 642.1812.
1.9.6. 3-{4-[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranos-
yl)-1H-1,2,3-triazol-4-yl]phenyl}-5-methyl-1,2,4-oxadiaz-
ole (18). Prepared from 12 (373 mg) and 3b (202 mg);
446 mg (80%); colorless solid; mp 230 ꢁC; Rf 0.75
1.9.11. 5-(4-{[1-(2,3,4,6-Tetra-O-acetyl-a-D-glucopyranos-
yl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-3-phenyl-1,2,4-
oxadiazole (28). Prepared from 1a (303.6 mg) and 24
(373 mg); 435 mg (67%); colorless solid; mp 109 ꢁC; Rf
20
(EtOAc); ½aꢁD ꢀ65 (c 1.0, CH2Cl2). Anal. Calcd for
20
C25H27N5O10: C, 53.86; H, 4.88. Found: C, 53.09; H,
4.96.
0.2 (3:2 petroleum ether–EtOAc); ½aꢁD +79 (c 1.0,
CH2Cl2). Anal. Calcd for C31H31N5O11: C, 57.32; H,
4.81. Found: C, 56.94; H, 4.82.
1.9.7. N-{[1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-
1H-1,2,3-triazol-4-yl]methyl}-4-(5-phenyl-1,2,4-oxadiazol-
3-yl)aniline (19). Prepared from 12 (373 mg) and 4
(302 mg); 434.5 mg (67%); colorless solid; mp 201 ꢁC;
1.10. 3-Biphenyl-4-yl-5-(4-{[1-(2,3,4,6-tetra-O-acetyl-b-
D-glucopyranosyl)-1H-1,2,3-triazol-4-yl]methoxy}phen-
yl)-1,2,4-oxadiazole (20)
20
Rf 0.63 (EtOAc); ½aꢁD ꢀ24 (c 1.0, CH2Cl2). Anal. Calcd
for C31H32N6O10: C, 57.40; H, 4.97; N, 12.96. Found: C,
57.28; H, 4.96; N, 12.67.
Pd(OAc)2 (0.3 mg, 1.1 lmol) and PPh3 (0.9 mg,
3.3 lmol) were placed in a flask under argon. Degassed
water (0.5 mL) and ethanol (0.5 mL) were added, and
the soln was stirred for 30 min at rt. A suspension of
bromooxadiazole 14 (80 mg, 0.11 mmol) and phenylbo-
ronic acid (15 mg, 0.12 mmol) in a mixture of toluene
(3 mL) and ethanol (1.5 mL) was then added to the
flask, followed by Na2CO3 (35 mg, 0.33 mmol) dissolved
in water (1 mL). The resulting mixture was stirred at
70 ꢁC for 16 h. The two phases were separated, the eth-
anol–water layer was washed twice with toluene. The
combined organic phases were dried over Na2SO4, and
concentrated under diminished pressure. Purification
of the crude product by chromatography on silica gel
using petroleum ether–EtOAc (3:2) as the eluent gave
the coupling product 20 (35 mg, 44%) as a colorless so-
lid: mp 237 ꢁC; Rf 0.36 (3:2 petroleum ether–EtOAc);
1.9.8. 5-(4-{[1-(3,4,6-Tri-O-acetyl-2-acetylamino-2-deoxy-
b-D-glucopyranosyl)-1H-1,2,3-triazol-4-yl]methoxy}phen-
yl)-3-phenyl-1,2,4-oxadiazole (25). Prepared from 1a
(303.6 mg) and 21 (372 mg); 408.6 mg (63%); colorless
20
solid; mp 246 ꢁC; Rf 0.44 (EtOAc); ½aꢁD ꢀ44 (c 0.5,
CH2Cl2); HRESIMS: m/z 671.2071. Calcd for
C31H32N6O10Na [M+Na]+: 671.2077.
1.9.9.
5-(4-{[1-(2,3,4,6-Tetra-O-acetyl-b-D-galactopyr-
anosyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-3-phenyl-
1,2,4-oxadiazole (26). Prepared from 1a (303.6 mg)
and 22 (373 mg); 389 mg (70%); colorless solid: mp
20
187 ꢁC; Rf 0.37 (7:3 EtOAc–petroleum ether); ½aꢁD ꢀ15
(c 1.0, CH2Cl2). Anal. Calcd for C31H31N5O11: C,
20
57.32; H, 4.81. Found: C, 57.03; H, 4.78.
½aꢁD ꢀ29 (c 0.5, CH2Cl2); HRESIMS: m/z 748.2236.
Calcd for C37H35N5O11Na [M+Na]+: 748.2231.
1.9.10.
5-(4-{[1-(2,20,3,30,40,6,60-Hepta-O-acetyl-b-D-
cellobiosyl)-1H-1,2,3-triazol-4-yl]methoxy}phenyl)-1,2,4-
oxadiazole (27). Prepared from 1a (303.6 mg) and 23
(661 mg); 591 mg (63%); colorless solid; mp 233 ꢁC; Rf
Acknowledgments
20
We are indebted to the CAPES/COFECUB Program
No. 334/01 for financial support, and CNPq-Brazil for
providing a fellowship (J.V.d.A.).
0.32 (7:3 EtOAc–petroleum ether); ½aꢁD ꢀ27 (c 1.0,
1
CH2Cl2); H NMR (CDCl3): d 1.85 (s, 3H, OAc), 1.99
(s, 3H, OAc), 2.02 (s, 3H, OAc), 2.04 (s, 3H, OAc),
2.05 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.11 (s, 3H,
OAc), 3.68 (ddd, 1H, J 9.6, 4.2, 2.3 Hz, H-50), 3.93–
3.98 (m, 2H, H-5, H-6), 4.05 (dd, 1H, J 12.4, 2.3 Hz,
H-60), 4.16 (dd, 1H, J 12.4, 4.2 Hz, H-60), 4.38 (dd,
1H, J 12.4, 4.2 Hz, H-6), 4.54 (dd, 1H, J 8.1, 7.9 Hz,
H-3), 4.57 (d, 1H, J 8.1 Hz, H-10), 4.96 (dd, 1H, J 9.0,
8.1 Hz, H-20), 5.08 (dd, 1H, J 9.6, 9.4 Hz, H-40), 5.17
(dd, 1H, J 9.4, 9.0 Hz, H-30), 5.31 (s, 2H, CH2O),
5.36–5.44 (m, 2H, H-4, H-2), 5.83 (d, 1H, J 8.8 Hz,
H-1), 7.13 (d, 2H, J 8.9 Hz, Harom), 7.49–7.52 (m, 3H,
Supplementary data
Supplementary data associated with this article can be
found, in the online version, at doi:10.1016/j.carres.
2007.07.011.
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