Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: Evaluation of the xylose scaffold for the design of potential glycogen phosphorylase inhibitors

Article abstract of DOI:10.1016/j.carres.2012.09.020

Various acetylenic derivatives and acetylated β-d-xylopyranosyl azide or the 5-thio-β-d-xylopyranosyl analogue were coupled by Cu(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition (CuAAC) to afford a series of 1-xylosyl-4-substituted 1,2,3-triazoles. Controlled oxidation of the endocyclic sulfur atom of the 5-thioxylose moiety led to the corresponding sulfoxides and sulfones. Deacetylation afforded 19 hydroxylated xylose and 5-thioxylose derivatives, found to be only sparingly water-soluble. Compared to glucose-based analogues, they appeared to be much weaker inhibitors of glycogen phosphorylase, as the absence of a hydroxymethyl group weakens their binding at the enzyme active site. However, such new xylose derivatives might be useful glycomimetics.

Full text of DOI:10.1016/j.carres.2012.09.020

Carbohydrate Research 364 (2012) 28–40
Contents lists available at SciVerse ScienceDirect
Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of
the xylose scaffold for the design of potential glycogen phosphorylase inhibitors
David Goyard a, Marc Baron a, Paraskevi V. Skourti b, Aikaterini S. Chajistamatiou b, Tibor Docsa c,
b,
a,
a,
Pál Gergely c, , Evangelia D. Chrysina , Jean-Pierre Praly , Sébastien Vidal
⇑
⇑
⇑
⇑
a Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2, Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, 43 Boulevard
du 11 Novembre 1918, F-69622 Villeurbanne, France
b Institute of Biology, Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 48 Vassileos Constantinou Avenue, Athens GR-11635, Greece
c Cell Biology and Signalling Research Group, Department of Medical Chemistry, Research Centre for Molecular Medicine, University of Debrecen, Nagyerdei krt. 98, H-4032
Debrecen, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 7 August 2012
Received in revised form 24 September 2012
Accepted 26 September 2012
Available online 5 October 2012
Various acetylenic derivatives and acetylated b-D-xylopyranosyl azide or the 5-thio-b-D-xylopyranosyl
analogue were coupled by Cu(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition (CuAAC) to afford a
series of 1-xylosyl-4-substituted 1,2,3-triazoles. Controlled oxidation of the endocyclic sulfur atom of
the 5-thioxylose moiety led to the corresponding sulfoxides and sulfones. Deacetylation afforded 19
hydroxylated xylose and 5-thioxylose derivatives, found to be only sparingly water-soluble. Compared
to glucose-based analogues, they appeared to be much weaker inhibitors of glycogen phosphorylase,
as the absence of a hydroxymethyl group weakens their binding at the enzyme active site. However, such
new xylose derivatives might be useful glycomimetics.
Keywords:
Xylose
Sulfoxide
Cycloaddition
1,2,3-Triazole
Glycogen phosphorylase
Ó 2012 Elsevier Ltd. All rights reserved.
1. Introduction
the anomeric position of the sugar including heterocyclic moieties
(e.g., oxadiazoles20–25 or triazoles26,27) that interact with amino-
As diabetic states result in hyperglycemia, which entails diverse
complications if untreated,1 symptomatic control of type 2 diabetes2
(diabetes mellitus) is managed based on several families of currently
marketed molecules,3–6 that differ in terms of pharmacological tar-
get, limitations, and side effects.7–9 The rising prevalence of type 2
diabetes2 is another concern, calling for the identification and vali-
dation of new therapeutic targets. Among the numerous biological
processes addressed by anti-diabetic strategies, glycogen phosphor-
ylase (GP) inhibition appeared as a promising approach for the
development of anti-hyperglycemic drugs.10–13
acid residues present in the so-called b-channel of the enzyme,
in the vicinity of the catalytic site.
While a large set of data has been collected from in vitro exper-
iments involving kinetic and structural studies of GP enzyme in the
presence of various ligands, additional data from in vivo
assessment of potent inhibitors are needed to confirm the potential
therapeutic applications of such molecules.28–30 N-Acetyl
b-D-glucopyranosylamine (1-GlcNAc, Fig. 1) was among the first
molecules evaluated for anti-hyperglycemic properties targeting
GP.31 The study highlighted a potent inhibition in vitro with a Ki
Glycogen phosphorylase is a homodimeric enzyme14 that cata-
lyzes the phosphorolysis (glycogenolysis15) of glycogen, the poly-
meric storage form of glucose. The inhibition of GP with small
molecules would therefore provide a useful tool for a better control
of glycemia for type 2 diabetic patients.10–13 Glucose-based mole-
cules represent the main class of GP inhibitors designed to date
and display potent inhibition against the enzyme with Ki values
in the sub-micromolar range.16–19 These molecular scaffolds are
composed of a glucopyranose ring that binds selectively at the
catalytic site of GP and a variety of substituents introduced at
value of 32 l
M31 against rabbit muscle glycogen phosphorylase b
(RMGPb) while no effect was observed in vivo.32 This observation
was explained by the metabolization of such glucose derivatives
through phosphorylation at the 6-position of the glucopyranose
ring leading to the 6-phosphoglucose species (1-GlcNAc-6-P).32
This phosphate derivative was shown to inhibit glycogen-bound
protein phosphatase 133 and to exert inhibitory effects through dif-
ferent modes for GPa and GSb (inactive phosphorylated glycogen
synthase). These data account for the fact that 1-GlcNAc prevents
the glucose-led activation of GS in whole hepatocytes.
The design of original molecular scaffolds closely related to glu-
copyranose but non-phosphorylatable at the 6-position should
provide GP inhibitors with improved in vivo biological properties.
⇑
Corresponding authors. Tel.: +33 472 431 161; fax: +33 472 432 752.
E-mail address: jean-pierre.praly@univ-lyon1.fr (J.-P. Praly).
0008-6215/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.carres.2012.09.020

D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
29
tions concerning both xylosyl and 5-thio-xylosyl derivatives
provided additional incentives for engaging in the work reported
next.
O
O
O
P
OH
O
H
N
H
N
O
O
HO
HO
HO
HO
Me
Me
2. Results and discussion
OH
OH
O
O
Although the synthetic methodology used in the present study
was similar to previously reported procedures, the biological activ-
ities targeted were very different and only a few substituents were
selected as potential pharmacophores for the catalytic site of GP.
N-Acetyl β-D-glucopyranosylamine
In vitro
N-Acetyl 6-phospho-glucopyranosylamine
Ki = 32 µM
against RMGPb
Peracetylation of D-xylose afforded the peracetyl protected xylopy-
ranose 1 which was readily converted into the bromo xylose deriv-
ative 2 (Scheme 1). Azidation of the anomeric position provided
Figure 1. N-Acetyl b-D-glucopyranosylamine (1-GlcNAc) as a potent GP inhibitor
prone to phosphorylation in hepatocytes.
the b-D-xylopyranosyl azide 3. 1,3-Dipolar cycloaddition of azide
3 with alkynes gave the corresponding acetylated 1,2,3-triazoles
4a–g which upon deprotection of the ester groups under Zemplén
conditions afforded the desired hydroxylated potential GP inhibi-
tors 5a–g.
One of the obvious targets is therefore the xylopyranose motif
(Fig. 2) in which the absence of the hydroxymethyl group (located
at the 5-position of glucose) prevents the problematic phosphory-
lation from occurring.32 Even though xylose does not inhibit GP,34
1-xylopyranosylated 1,2,3-triazoles (A, X = O) were selected since
recent reports have demonstrated the in vitro potent inhibition
of GP with their glucose analogues.26,27 The triazole ring can be ob-
tained from the four chemically accessible protected xylosyl azide
derivatives (B, X = O, S, SO, and SO2) and terminal alkynes (C)
through Cu(I)-catalyzed azide alkyne 1,3-dipolar cycloaddition35–37
(CuAAC). The four molecular scaffolds based on the xylose struc-
ture would provide a family of potential GP inhibitors with differ-
ent atom patterns at the endocyclic oxygen atom position that
could assign interesting different inhibitory properties against
the enzyme. Replacement of the ring oxygen atom by a sulfur atom
offered additional structural modifications through oxidation (to-
ward sulfoxides and sulfones) or by alkylation to form sulfonium
derivatives. The four endocyclic variants of the xylose ring (O, S,
SO, and SO2) were expected to result in related potential GP inhib-
itors which could display enhanced inhibitory properties, if these
unusual features participate in additional stabilizing interactions
at the enzyme active site in ligand–enzyme complexes. As this
strategy has been essentially unexplored, this investigation offered
a possibility for exploring whether modifications introduced in the
sugar would lead to stronger inhibitors as previously studied for 5-
thio-glucose.38,39
Similar synthesis was performed in the 5-thioxylose series
(Scheme 2). a
-Bromide 653 was converted into the 5-thioxylopyr-
anosyl azide 7.54 Oxidation of the sulfur atom was undertaken in
order to expand the family of potential GP inhibitors with sulfox-
ides and sulfones. The mixture of azido-sulfoxides 8 was prepared
from 7 by oxidation with m-chloroperoxybenzoic acid (m-CPBA) in
slight excess (1.2 equiv), and under different conditions (Table 1).
The diastereoselectivity of the oxidation was always in favor of
the equatorial sulfoxide (i.e., S stereochemistry at the sulfur atom).
The best conditions (THF, room temperature, 15 min) provided a
ꢀ4:1 diastereoisomeric mixture of sulfoxides 8. This constitutes
the first clear-cut example of solvent influencing the stereoselec-
tivity of oxidation leading to glycosulfoxides.55 The parameters
that might influence the oxidation of sulfur atoms (attached to
either the C-1,56,57 the C-5,58,57 or both positions59) have been
envisaged, but the diastereocontrol issues remain complex. The
stereochemical assignment of each isomer of 8 was proposed from
comparison with NMR spectroscopy data reported for 5-thioglu-
cose,55 and 5-thio-xylose60 derivatives, which were studied by X-
ray diffraction analysis.
Sulfoxides 8-R and 8-S could not be readily separated by silica
gel chromatography but a small portion of each pure compound
could be isolated for NMR studies (Table 2). Their stereochemistry
was deduced based on data reported for the oxidation of 5-thioglu-
cose by m-CPBA with assignment of the sulfoxides structures by
crystal analysis. Comparison of their 1H NMR chemical shifts55
showed the deshielding effect exerted by lone electron pairs of
the sulfoxide oxygen atom on neighboring protons, as schemati-
cally represented on the Newman representations of each diaste-
reoisomer 8-R and 8-S (Fig. 3). As seen from the 1H NMR data
collected for each sulfoxide 8-R and 8-S (Table 2), the proton sig-
It is to be mentioned that the synthetic values of glycosyl
azides40 for preparing various glycosyl-heterocycles41,42 is well-
recognized.26,27 The CuAAC approach gives access to multivalent
glycoconjugates under one-pot conditions,43,44 to novel glycolip-
ids,45 or to sugar-based triazole derivatives studied as glycosidic
carbonic anhydrase inhibitors.46 Xylose derivatives are of special
interest, as a xylopyranosyl unit occupies a key position in the pro-
teoglycan linkage tetrasaccharide sequence, by joining the protein
core to the polysaccharide side chains. Consequently, xylose-based
triazoles have been considered for studying the biosynthesis of gly-
nals for H-2 and H-4 of sulfoxide 8-R moved downfield by a
Dd
cosaminoglycans,47,48 while a number of 5-thio-
tives have been evaluated as oral antithrombotic drugs.49
Recently, -arabinofuranosyl-triazoles bearing various alkyl chains
D-xylosyl deriva-
of +0.71 and +0.66 ppm, respectively in comparison to the azide
7, while they remained almost unchanged for the other diastereo-
isomer 8-S.55 Moreover, for 8-R, the chemical shifts of protons H1
(d = 4.09) and H-5ax (d = 2.65) both anti-parallel to the axial sulfox-
ide bond were shifted upfield, compared to their counterparts in
diastereoisomer 8-S (d = 4.48 and 3.06 ppm, respectively, Fig. 4).
D
were tested as inhibitors of the mycobacterial cell wall biosynthe-
sis.50 Both 1-glycosyl-4-phenyl triazoles,51 and thiasugars52 have
been evaluated as glycosidase inhibitors. These valuable informa-
1,3-Dipolar
Cycloaddition
N
N
N
R
X
X
PO
PO
R
HO
HO
N3
+
OP
[3+2]
X = O, S, SO, SO2
OH
A
B
C
Figure 2. Synthetic strategy for the preparation of xylose-based inhibitors of GP.

30
D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
Table 1
O
O
Ac2O / DMAP
C5H5N
NaN3
AcO
AcO
AcO
Oxidation of azido 2,3,4-tri-O-acetyl-5-thioxylopyranose 7a
N3
D-Xylose
AcO
R
DMSO
AcO
OAc
Solvent
Temperature
Time (min)
Conversionb (%)
Selectivityc
OAc
CuI / DMF
iPr2NEt
100°C
3
X
1
2
X =
DMEd
DMF
CH2Cl2
Dioxane
Et2O
23 °C
23 °C
23 °C
23 °C
23 °C
ꢁ78 °C
23 °C
15
15
15
15
15
60
15
75
75
63
76
75
33
85
60:40
60:40
70:30
73:27
79:21
82:18
83:17
HBr / AcOH
X = Br
N
N
N
N
R
R
O
MeONa
O
HO
HO
AcO
AcO
N
N
THF
THF
MeOH / DMF
OH
OAc
a
5a R = CH2OH
5b R = Ph
4a R = CH2OAc
4b R = Ph
Conditions: 7 (100 mg, 0.32 mmol), m-CPBA (1.2 equiv) solvent (5 mL). Longer
reaction times did not afford higher conversion rates.
5c R =
4c R =
4-O2NPh
4-O2NPh
b
A portion of the starting material could be recovered after silica gel column
5d R = 4-MePh
5e R = 4-MeO-2-MePh
5f R =
4d R = 4-MePh
4e R = 4-MeO-2-MePh
4f R =
chromatography.
c
2-naphthyl
5g R = 6-MeO-2-naphthyl
2-naphthyl
4g R = 6-MeO-2-naphthyl
Determined as the ratio of equatorial to axial sulfoxides 8 from their respective
integration of 1H NMR signals.
d
DME = 1,2-dimethoxyethane.
Scheme 1. Synthesis of 1-xylopyranosyl-4-substituted 1,2,3-triazoles 5a–g.
MeOH) or solvolysis (Et3N/MeOH/H2O) afforded complex mixtures
of compounds.
The attempted CuAAC conjugation of the azido-sulfoxides 8
with alkynes did not afford the desired triazoles but instead pro-
vided an undefined mixture of products. The sulfoxide zwitterionic
moiety was probably chelating the Cu(I) catalyst thus preventing
the cycloaddition process. 1,3-Dipolar cycloaddition was therefore
performed with the azide 7 to afford the desired triazoles 9a–j in
high yields. The subsequent deacetylation using standard Zemplén
conditions provided the hydroxylated 1-(5-thioxylopyranosyl)-4-
substituted 1,2,3-triazoles 10a–j. The oxidation of the 5-thioxylose
sulfur atom was then performed on 1,2,3-triazoles 9a,b using a
slight excess of m-CPBA (1.2 equiv) to afford a 83:17 diastereoiso-
meric mixture of sulfoxides 11a,b. Access to the sulfone function-
ality was initially attempted from 9a using a large excess of
m-CPBA (20 equiv) but the 1,2-glycal derivative 13 was obtained
as the sole product, probably through the elimination of acetic acid
during the workup under basic conditions. The oxidation of 9a,b
was then performed with ammonium molybdate, which did not re-
quire a basic workup thus allowing for the isolation of the desired
sulfones 14a,b in high yields. Both sulfoxides 11a,b and sulfones
14a,b were deprotected under acidic methanolysis to afford the
corresponding hydroxylated GP inhibitor candidates 12a,b and
15a,b respectively while standard Zemplén conditions (MeONa/
A total of 21 potential inhibitors of GP were synthesized in a ra-
pid and efficient synthetic route and afforded seven 1-xylopyrano-
syl 1,2,3-triazoles 5a–g, 10 1-(5-thioxylopyranosyl) 1,2,3-triazoles
9a–h along with two sulfoxides 12a,b and two sulfones 15a,b. The
inhibitory potency against rabbit muscle glycogen phosphorylase b
(RMGPb) was determined for 19 of these inhibitors (Table 3). The
xylose-based compounds 5a–g were evaluated at a maximum con-
centration of 625 lM and did not display any inhibition toward
RMGPb apart from a very poor inhibition observed for the p-tolyl
substituted derivative 5d. The corresponding glucose-based inhib-
itors recently reported displayed inhibitions in the micromolar
range26,27 with the hydroxymethyl and 2-naphthyl residues as
the best pharmacophores for this enzyme (Fig. 5, Table 3). The ab-
sence of the hydroxymethyl moiety in the xylose-based inhibitors
5a–g was therefore responsible for a severe loss of interactions
with the enzyme’s catalytic site resulting in very poor ligands.
The 5-thioxylose derivatives 10a–h were also quite poor inhibitors
of RMGPb since less than 20% inhibition was observed at a concen-
tration of 1 mM and only the hydroxymethyl substituted inhibitor
10a could provide an IC50 value of 1.5 mM. The low inhibitions
observed are probably also related to the poor solubility of
O
S
S
S
NaN3
AcO
AcO
AcO
AcO
m-CPBA AcO
N3
N3
AcO
DMSO
AcO
OAc
OAc
R1 = 2-naphthyl
7
8
Br
6
a
b
c
d
e
R1 = CH2OAc
f
R
1 = Ph
g
h
i
R
1 = 6-MeO-2-naphthyl
=
=
=
CuI / DMF
iPr2NEt
100°C
R1
R1
R1
=
=
=
R1
R1
R1
4-O2NPh
4-MePh
4-MeO-2-MePh
4-MeOPh
C6H11
cyclohexen-1-yl
R1
j
O
N
N
N
N
N
R1
R1
m-CPBA
R2O
R2O
R2O
S
S
N
R2O
1.5 eq.
OR2
OR2
MeONa
MeOH
DMF
9a-j R2
10a-j R2
=
=
Ac
H
11a-b R2
=
=
Ac
H
MeOH
AcCl cat.
12a-b R2
m-CPBA
H2O2
10a, 12a, 15a R1 = CH2OH
20 eq.
(NH4)2Mo7O24 4H2O
O
S
O
S
N
N
R1
AcO
AcO
R2O
O
O
R2O
N
+
N
N
N
OR2
13
14a-b
15a-b R2
R
2 = Ac
=
H
MeOH
AcCl cat.
OAc
Scheme 2. Synthesis of 1-(5-thioxylopyranosyl)-4-substituted 1,2,3-triazoles 10a–j and related sulfoxide and sulfone analogues 8, 12a,b, 15a,b.

D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
31
Table 2
Chemical shifts (d in ppm, 300 MHz, CDCl3) for the proton signals of azido 2,3,4-tri-O-acetyl-5-thio-b-D-xylopyranose 7 and the corresponding sulfoxides 8-R and 8-S
S
O
S
S
O
AcO
AcO
AcO
AcO
N3
N3
AcO
AcO
OAc
OAc
N3
8-S
7
OAc
8-R
H-1
H-2
H-3
H-4
H-5ax
H-5eq
4.48
5.07
5.15
5.04
2.70
2.94
4.09
5.78
5.35
5.70
2.65
3.63
D
D
D
D
D
D
d = ꢁ0.39
d = +0.71
d = +0.20
d = +0.66
d = ꢁ0.05
d = +0.69
4.48
5.01
5.35
5.04
3.06
3.72
D
D
D
D
D
D
d = 0.00
d = ꢁ0.06
d = +0.20
d = 0.00
d = +0.36
d = +0.78
O
S
S
O
AcO
AcO
AcO
N3
N3
AcO
OAc
OAc
8-R
8-S
H-4
C-4
H-4
C-4
H-2
O
H-2
AcO
H-5e
AcO
H-5e
O
C-2
S
C-2
S
AcO
AcO
C-1
H-1
C-1
H-1
H-3
H-5a
H-3
H-5a
Figure 3. Newman representations of the sulfoxides 8-R and 8-S.
Figure 4. Partial 1H NMR data (300 MHz, CDCl3) for sulfoxides 8-R (bottom) and 8-S (top).

32
D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
Table 3
of alkynes to the corresponding D-xylopyranosyl azide. Oxidation
Inhibition of rabbit muscle glycogen phosphorylase b (RMGPb) by the synthesized
(thio)xylosyl triazoles
of the sulfur atom afforded the sulfoxide and sulfone analogues
in good yields. Deacetylation led to twenty one structures found
only poorly or even not water-soluble, from which 19 candidates
have been evaluated as RMGPb inhibitors. The inhibitory potency
exhibited was very modest (in the mM range), much weaker com-
Scaffold
Xylose
Compound
Inhibition IC50 (lM)
5a
5b
5c
5d
NIa
NIa
NIa
pared to
D-glucose-based analogues. The
D-xylose scaffold should
15%b
prevent the O-phosphorylation observed in vivo for
D
-glucopyr-
5e
NIa
anosylamines at the 6-position with detrimental consequences.
However, the absence of a hydroxymethyl substituent at the 5-po-
sition in the xylose-based triazoles was highly detrimental in
terms of water-solubility and binding to the catalytic site of GP,
resulting in no or poor inhibition of the enzyme. Although a
5f
5g
n.d.
NIa
5-Thioxylosee
10a
10b
10c
10d
10e
10f
10g
10h
12ae
12b
15a
15b
16a
16b
16f
1526 156
15%c
15%b
5%b
2%b
slightly reduced inhibitory potency, compared to that of
D-gluco-
18%b,
c
pyranose, was anticipated due to the -xylopyranose motif, the
D
NI @ 500
Insoluble
NIf
quest for a more favorable heterocyclic moiety to compensate for
the modification of the glucose moiety did not meet our expecta-
tions. However, the xylose-, and 5-thioxylose-based derivatives re-
ported herein might have potential for other biomedicinal
developments which are associated to important health issues.
5-Thioxylose Sulfoxided
5-Thioxylose Sulfoned
Glucose
n.d.
NIf
14%b
26g
162g
36g
4. Experimental section
4.1. General methods
a
b
c
No inhibition at 625
Inhibition observed at 625
Inhibition potency probably underestimated since centrifugation was required
lM.
lM.
to remove insoluble material at a concentration 10 mM in 20% DMSO.
All reagents and solvents used for syntheses were commercial
and used without further purification. Solvents were distilled over
CaH2 (CH2Cl2), Mg/I2 (MeOH), or purchased dry. Reactions were
performed under argon atmosphere. NMR spectra were recorded
at 293 K, unless stated otherwise, using a 300 MHz, a 400 MHz or
a 500 MHz spectrometer. Shifts are referenced relative to deuter-
ated solvent residual peaks. Low and high resolution mass spectra
were recorded in the positive mode using a Bruker MicrOTOF-Q II
XL spectrometer. Thin-layer chromatography (TLC) was carried out
on aluminium sheets coated with silica gel 60 F254 (Merck). TLC
plates were inspected by UV light (k = 254 nm) and developed by
treatment with a solution of 10% H2SO4 in EtOH/H2O (1:1 v/v) or
KMnO4 in H2O or ninhydrin in n-BuOH/H2O followed by heating.
Silica gel column chromatography was performed with silica gel
d
All compounds were initially dissolved in 100% DMSO and suitable dilutions
were prepared for kinetic experiments to be performed in the presence of 1–2%
DMSO.
e
65:35 Mixture of diastereoisomers.
f
No inhibition at 1000
l
M.
g
Ki values were reported by Bokor et al.26 (n.d. = not determined).
N
OH
N
N
R
O
HO
HO
OH
Ki = 26 µM
Ki = 162 µM
2-Naphthyl Ki = 36 µM
16a R = CH2OH
16b R =
16f R =
Ph
Si 60 (40–63
lm). Optical rotations were measured using a Perkin
Elmer polarimeter and values are given in 10ꢁ1 deg cm2 gꢁ1
.
Figure 5. Glucose-based inhibitors of glycogen phosphorylase and their inhibition
toward RMGPb.
4.2. General procedure A for the preparation of 1-(2,3,4-tri-O-
acetyl-b- -xylopyranosyl)-4-substituted-1,2,3-triazoles (4a–g)
D
compounds 10a–h in water. Although the water solubility of the
sulfoxides 12a,b and sulfones 15a,b was less critical, the inhibi-
tions measured for these compounds were still disappointing. A
comparison of the inhibitory properties of the hydroxymethylated
derivatives 5a, 10a, 12a and 15a revealed neither an influence of
the xylose/thioxylose scaffold nor that of the sulfur oxidation state
on the inhibition of RMGPb. The cyclohexane and cyclohexene-1-yl
substituted derivatives 10i and 10j were not evaluated as RMGPb
inhibitors due to the low potencies observed for the other com-
pounds 10a–h and since non-aromatic substituents usually do
not perform well in interacting with the b-channel of GP. In our
hands, a few attempts aiming at the synthesis of xylose-based sul-
fonium derivatives failed. Considering the limitations associated to
A
solution of 2,3,4-tri-O-acetyl-b-D-xylopyranosyl azide 3
(150 mg, 0.5 mmol) and CuI (47 mg, 0.25 mmol, 0.5 equiv) in dry
DMF (10 mL) was stirred under argon. Then a selected alkyne
was added (1.0 mmol, 2 equiv) followed by the addition of iPr2NEt
(2.49 mmol, 0.435 mL, 5 equiv). The solution was stirred at 100 °C
under argon and the reaction was completed within ꢀ1 h as mon-
itored by TLC (EtOAc/PE 1:1). The mixture was cooled to rt then di-
luted with EtOAc (70 mL). The organic layer was washed with
aqueous solutions (HCl 1 N, then saturated Na2CO3, finally satu-
rated NaCl—3 ꢂ 30 mL in each case), dried, (MgSO4) and concen-
trated to dryness to afford a solid residue which was washed
with MeOH (<5 mL). After solvent removal under vacuum, the sol-
ids obtained were found analytically pure by TLC and NMR analy-
ses (1H and 13C).
the D-xylose scaffold (weak water-solubility) and the poor inhibi-
tion observed with the tested compounds, this route was not
investigated further.
4.3. General procedure B for the preparation of
1-(b-D-xylopyranosyl)-4-substituted-1,2,3-triazoles (5a–g)
3. Conclusion
The acetylated xylo-triazole (4a–g, 0.5 mmol) was dissolved in
dry MeOH (15 mL) and dry DMF (5 mL or more according to
The synthesis of xylose- and 5-thioxylose-based 1,2,3-triazole
inhibitors of GP was achieved through 1,3-dipolar cycloaddition

D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
33
solubility). After addition of sodium methoxide (0.3 equiv), the
solution was stirred under argon atmosphere. Monitoring by TLC
(EtOAc/MeOH 9:1) showed that completion was reached usually
within one day. The reaction mixture was treated with IR-120
ion-exchange resin (H+ form). The resin was filtered off and
washed with MeOH (2 ꢂ 5 mL). The filtrate was concentrated and
co-evaporated several times with toluene to give a solid which
was washed with CH2Cl2 (2 ꢂ 2 mL). After removal of the solvents
under high vacuum, the product examined by NMR (1H and 13C)
was found analytically pure.
with water (20 mL) and extracted with CH2Cl2 (3 ꢂ 25 mL). The or-
ganic layers were combined, washed with Na2S2O3 10% in water
(3 ꢂ 50 mL), water (2 ꢂ 50 mL), dried (MgSO4), and concentrated
in vacuo. The crude product was purified by silica gel chromatog-
raphy (CH2Cl2/EtOAc 9:1) to afford 1-(2,3,4-tri-O-acetyl-5-thio-b-
D-xylopyranosyl)-4-substituted-1,2,3-triazole S,S-dioxide 14a,b.
4.8. General procedure G for the deacetylation of thioxylose-
based sulfoxides and sulfones under acidic conditions
To a solution of acetylated derivatives in a mixture of dry THF
and dry MeOH (10 mL/100 mg, 1:1) was added acetyl chloride
4.4. General procedure C for the synthesis of 1-[2,3,4-tri-O-
acetyl-5-thio-b-
D
-xylopyranosyl]-4-substituted-1,2,3-triazoles
(100 lL/100 mg) at 0 °C. The mixture was stirred at rt overnight
(9a–j)
and concentrated in vacuo to afford the desired deacetylated
product.
A
suspension of 2,3,4-tri-O-acetyl-5-thio-b-D-xylopyranosyl
azide 7 (200 mg, 0.63 mmol, 1 equiv), CuI (11 mg, 0.06 mmol,
4.9. Glycogen phosphorylase inhibition measurements
0.1 equiv) and alkyne (1.26 mmol, 2 equiv) in dry DMF (5 mL)
was sonicated for a few seconds. Then DIPEA (823
l
L, 4.73 mmol,
Kinetic experiments were performed as described previously for
the xylose-based analogues 5a–g61 and for the other sulfur-con-
taining analogues.62
7.5 equiv) was added and the mixture was stirred for 2 h at
110 °C. The mixture was then diluted with EtOAc (100 mL), washed
with 1 N HCl (2 ꢂ 50 mL), saturated NaHCO3 (2 ꢂ 50 mL), water
(2 ꢂ 50 mL), brine (2 ꢂ 50 mL), dried (MgSO4), and concentrated
in vacuo. The crude product was suspended in a minimum of
CH2Cl2 (ꢀ5 mL), precipitated with petroleum ether and filtered to
4.10. 1-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-4-acetoxymethyl-
1,2,3-triazole (4a)
afford analytically pure 1-(2,3,4-tri-O-acetyl-5-thio-b-
anosyl)-4-substituted-1,2,3-triazoles 9a–j.
D-xylopyr-
The title compound was prepared from 3 (291 mg, 0.97 mmol)
and propargyl acetate (291 mg, 2.97 mmol) which reacted, follow-
ing the general procedure A, at rt (because of the volatility of prop-
argyl acetate) and with a slower reaction rate (reaction time: 18 h).
It was isolated as yellow solid foam (297 mg, 0.74 mmol, 77%).
4.5. General procedure D for the synthesis of 5-thio-b-D-
xylopyranosyl-4-substituted-1,2,3-triazoles 10a–j
Rf = 0.75 (EtOAc/PE 1:1). ½a D20
ꢃ
ꢁ58.8 (c 1.0/CH2Cl2). 1H NMR (CDCl3,
Sodium methoxide (0.4 equiv) was added to a solution of
1-(2,3,4-tri-O-acetyl-5-thio-b- -xylopyranosyl)-4-(substituted)-1,2,
400 MHz): d = 7.81 (s, 1H, H-50), 5.77 (d, 1H, J = 8.8 Hz,H-1), 5.40 (t,
1H, J = 8.8 Hz, H-3), 5.35 (t, 1H, J = 8.8 Hz, H-2), 5.18 (s, 2H,
CH2OAc), 5.09–5.16 (m, 1H, H-4), 4.27 (dd, 1H, J = 11.6, 5.6 Hz, H-
5 eq), 3.58 (t, 1 H, J = 11.6 Hz, H-5ax), 2.05, 2.03, 1.86 (3s, 12H, acet-
yl). 13C NMR (CDCl3, 100 MHz): d = 171.0, 170.1, 170.0, 169.2 (4C,
C@O), 143.9 (C-40), 122.4 (C-50), 86.6 (C-1), 72.3 (C-3), 70.8 (C-2),
68.7 (C-4), 65.9 (C-5), 57.7 (CH2OAc), 21.1, 20.9, 20.9, 20.5 (4CH3,
acetyl). ESI-MS (positive mode) m/z: 422.1 [M+Na]+, 920.2
[2M+Na]+. HR-LSIMS-MS (positive mode) m/z: calculated for
C16H21N3O9 [M+Na]+ 422.1170, found 422.1171.
D
3-triazole 9a–j (1 equiv) in a DMF/MeOH (9:1) mixture (10 mL).
The mixture was stirred at room temperature overnight, neutral-
ized with Amberlite IR 120 resin, and filtered. The filtrate was con-
centrated under reduced pressure. The crude product was washed
with a minimum of methanol and filtered to give an analytically
pure product.
4.6. General procedure E for the synthesis of 5-thioxylose-based
sulfoxides 8 and 11a–b
4.11. 1-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-4-phenyl-1,2,3-
To a solution of azido 2,3,4-tri-O-acetyl-5-thio-b-
D-xylopyra-
triazole (4b)47
nose 7 or 1-(2,3,4-tri-O-acetyl-5-thio-b- -xylopyranosyl)-4-substi-
D
tuted-1,2,3-triazoles 9a,b (1 equiv) in dry THF (5 mL/0.3 mmol)
was added dropwise a solution of m-CPBA (1.2 equiv) in dry THF
(5 mL/0.4 mmol). The mixture was stirred at rt for 15 min, diluted
with EtOAc (50 mL) and washed successively with saturated
solutions of Na2S2O3 (50 mL), NaHCO3 (2 ꢂ 50 mL) and NaCl
(2 ꢂ 50 mL). The organic layer was dried (MgSO4), filtered, and
concentrated in vacuo. The crude product (white solid) was puri-
fied by silica gel chromatography (Et2O/CH2Cl2 9:1) to give a por-
tion of the starting material, a pure fraction of the less polar
sulfoxide (e.g., 8-S), a mixture of both diastereoisomeric sulfoxides
and a pure portion of the more polar sulfoxide (e.g., 8-R).
The title compound was prepared from 3 (147 mg, 0.49 mmol)
and phenylacetylene (0.11 mL, 1.0 mmol) according to general pro-
cedure A, and isolated as a white solid (158 mg, 0.39 mmol, 80%).
Rf = 0.53 (EtOAc/PE 1:1). Mp = 241–246 °C. ½a D20
ꢁ127.1 (c 1.0/
ꢃ
1
CH2Cl2). H NMR (CDCl3, 400 MHz): d = 7.98 (s, 1H, H-50), 7.84 (d,
2H, J = 7.2 Hz, H-Ar), 7.43 (t, 2H, J = 7.5 Hz, H-Ar), 7.37 (t, 1H,
J = 7.2 Hz, H-Ar), 5.84 (d, 1H, J = 4.8 Hz, H-1), 5.45 (m, 2H, H-2, H-
3), 5.15–5.23 (m, 1H, H-4), 4.33 (dd, 1H, J = 11.2, 5.8 Hz, H-5eq),
3.62 (t, 1H, J = 11.2 Hz, H-5ax), 2.08, 2.06, 1.89 (3s, 9H, acetyl); 13C
NMR (CDCl3, 100 MHz): d = 170.2, 170.1, 169.4 (3C@O, acetyl),
148.8 (C-40), 130.3 (C-Ar), 129.2 (2CH-Ar), 128.9 (CH-Ar), 126.2
(2CH-Ar), 117.9 (C-50), 86.6 (C-1), 72.5 (C-2) 70.7 (C-3), 68.8 (C-4),
66.0 (C-5), 21.0, 20.9, 20.6 (3CH3, acetyl). ESI-MS (positive mode)
m/z: 404.1 [M+H]+, 426.1 [M+Na]+. HR-LSIMS-MS (positive mode)
m/z: calculated for C19H21N3O7 [M+Na]+ 426.1272, found 426.1265.
4.7. General procedure F for the synthesis of thioxylose-based
sulfones (14a,b)
To a suspension of 1-(2,3,4-tri-O-acetyl-5-thio-b-D-xylopyrano-
syl)-4-substituted-1,2,3-triazole 9a,b (1 equiv) and ‘ammonium
molybdate’ (0.05 equiv) in dry ethanol (10 mL/0.5 mmol) was
added at 0 °C a solution of hydrogen peroxide 35% wt in water
(8 equiv). The mixture was stirred at 0 °C for 1 h, allowed to warm
up to rt and stirred for an additional 16 h. The mixture was diluted
4.12. 1-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-4-(4-
nitrophenyl)-1,2,3-triazole (4c)
The title compound was prepared from 3 (143 mg, 0.47 mmol)
and 4-nitrophenyl-ethynyl (147 mg, 1.0 mmol) according to the

34
D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
general procedure A, and isolated as a pale yellow solid (187 mg,
1H, J = 8.4 Hz, H-3), 5.20 (m, 1H, H-4), 4.35 (dd, 1H, J = 11.4,
6.0 Hz, H-5 eq), 3.65 (t, 1H, J = 11.4 Hz, H-5ax), 2.10, 2.07, 1.91
(3s, 9H, acetyl). 13C NMR (CDCl3, 100 MHz): d = 170.1, 170.1,
169.5 (3C, C@O), 133.8 (C-40), 133.7 (C-Ar), 133.4 (C-Ar), 129.0
(CH-Ar), 128.6 (CH-Ar), 128.1 (2CH-Ar), 127.5 (C-Ar), 126.9 (CH-
Ar), 126.7 (CH-Ar), 125.2 (CH-Ar), 124.1 (C-50), 86.9 (C-1), 72.5
(C-3), 70.8 (C-2), 68.8 (C-4), 66.0 (C-5), 21.0, 21.0, 20.6 (3CH3, acet-
yl). ESI-MS (positive mode) m/z: 476.1 [M+Na]+. HR-LSIMS-MS (po-
sitive mode) m/z: calculated for C23H23N3O7 [M+Na]+ 476.1428,
found 476.1422.
0.42 mmol, 88%). Rf = 0.52 (EtOAc/PE 1:1). Mp = 204–207 °C. ½a D20
ꢃ
ꢁ126.7 (c 1.0/CH2Cl2). 1H NMR (CDCl3, 400 MHz): d = 8.30 (d, 2H,
J = 9.0 Hz, H-Ar), 8.13 (s, 1H, H-50), 8.01 (d, 2H, J = 9.0 Hz, H-Ar),
5.86 (d, 1H, J = 9.3 Hz, H-1), 5.47 (t, 1H, J = 9.3 Hz, H-2), 5.42 (t,
1H, J = 9.3 Hz, H-3), 5.18 (ddd, 1H, J = 11.4, 9.3, 5.7 Hz, H-4), 4.35
(dd, 1H, J = 11.4, 5.7 Hz, H-5eq), 3.64 (t, 1H, J = 11.4 Hz, H-5ax),
2.09, 2.07, 1.91 (3s, 9H, acetyl). 13C NMR (CDCl3, 100 MHz):
d = 170.1, 170.0, 169.4 (3C, C@O), 147.7 (C-Ar), 146.5 (C-Ar),
136.4 (C-40), 126.6 (2CH-Ar), 124.6 (2CH-Ar), 119.5 (C-50), 86.8
(C-1), 72.1 (C-3), 70.8 (C-2), 68.6 (C-4), 66.0 (C-5), 20.9, 20.8, 20.5
(3CH3, acetyl). ESI-MS (positive mode) m/z: 471.1 [M+Na]+, 919.2
[2M+Na]+. HR-LSIMS-MS (positive mode) m/z: calculated for
C19H20N4O8 [M+Na]+ 471.1122, found 471.1115.
4.16. 1-(2,3,4-Tri-O-acetyl-b-
D-xylopyranosyl)-4-(6-methoxy-2-
naphthyl)-1,2,3-triazole (4g)
The title compound was prepared from 3 (144 mg, 0.48 mmol)
and 2-ethynyl-6-methoxynaphthalene (184 mg, 1.01 mmol)
according to the general procedure A, and isolated as a white solid
(186 mg, 0.38 mmol, 80%). Rf = 0.58 (EtOAc/PE 1:1). Mp = 247–
4.13. 1-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-4-(4-
methylphenyl)-1,2,3-triazole (4d)
The title compound was prepared from 3 (138 mg, 0.46 mmol)
and 4-tolyl-ethynyl (0.13 mL, 1.00 mmol) according to the general
procedure A, and isolated as a white solid (174 mg, 0.42 mmol,
249 °C. ½a 2D0
ꢃ
ꢁ99.6 (c 1.0/CH2Cl2). 1H NMR (CDCl3, 400 MHz):
d = 8.29 (s, 1H, H-50), 8.08–8.14 (m, 1H, H-Ar), 7.70–7.90 (m, 3H,
H-Ar), 7.14–7.19 (m, 2H, H-Ar), 5.86 (d, 1H, J = 8.4 Hz, H-1), 5.50
(m, 1H, H-2), 5.45 (m, 1H, H-3), 5.20 (m, 1H, H-4), 4.34 (dd, 1 H,
J = 11.2, 5.6 Hz, H-5eq), 3.94 (s, 3H, OCH3), 3.64 (t, 1H, J = 11.2 Hz,
H-5ax), 2.09, 2.07, 1.91 (3s, 9H, acetyl). 13C NMR (CDCl3,
100 MHz): d = 170.2, 170.1, 169.5 (3C, C@O), 158.4 (C-Ar) 134.9
(C-Ar), 134.9 (C-Ar), 130.1 (CH-Ar), 129.3 (C-40), 127.8 (CH-Ar),
125.0 (C-50), 124.7 (2CH-Ar), 119.7 (CH-Ar), 106.1 (CH-Ar), 86.9
(C-1), 72.5 (C-3), 70.7 (C-2), 68.8 (C-4), 66.0 (C-5), 55.7 (OCH3),
21.0, 21.1, 20.6 (3CH3, acetyl). ESI-MS (positive mode) m/z: 483.9
[M+H]+, 506.0 [M+Na]+, 966.5 [2M+H]+, 988.8 [2M+Na]+, 1470.8
[3M+Na]+. HR-LSIMS-MS (positive mode) m/z: calculated for
91%). Rf = 0.51 (EtOAc/PE 1:1). Mp = 239–242 °C. ½a D20
ꢁ105.0 (c
ꢃ
1
1.0/CH2Cl2). H NMR (CDCl3, 400 MHz): d = 7.93 (s, 1H, H-50), 7.71
(d, 2H, J = 8.0 Hz, H-Ar), 7.23 (d, 2H, J = 8.0 Hz, H-Ar), 5.83 (d, 1H,
J = 8.8 Hz, H-1), 5.46 (t, 1H, J = 8.8 Hz, H-2), 5.43 (t, 1H, J = 8.8 Hz,
H-3), 5.18 (ddd, 1H, J = 11.6, 8.8, 5.6 Hz H-4), 4.31 (dd, 1H,
J = 11.6, 5.6 Hz, H-5eq), 3.62 (t, 1H, J = 11.6 Hz, H-5ax), 2.38 (s, 3H,
PhCH3), 2.08, 2.06, 1.88 (3s, 9H, acetyl). 13C NMR (CDCl3,
100 MHz): d = 170.2, 170.1, 169.4 (3C, C@O), 148.8 (C-40), 138.8
(C-Ar), 129.9 (2CH-Ar), 127.5 (C-Ar), 126.1 (CH-Ar), 117.6 (C-50),
86.7 (C-1), 72.5 (C-3), 70.7 (C-2), 68.8 (C-4), 65.9 (C-5), 21.6
(PhCH3), 21.0, 20.9, 20.6 (3CH3, acetyl). ESI-MS (positive mode)
m/z: 440.1 [M+Na]+. HR-LSIMS-MS (positive mode) m/z: calculated
for C20H23N3O7 [M+Na]+ 440.1428, found 440.1411.
C
24H25N3O8 [M+Na]+ 506.1534, found 506.1526.
4.17. 1-(b-D-Xylopyranosyl)-4-hydroxymethyl-1,2,3-triazole
(5a)47
4.14. 1-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-1,2,3-triazole-4-
(4-methoxy-2-methylphenyl) (4e)
The title compound was prepared from 4a (142 mg,
0.356 mmol) according to the general procedure B, and isolated
as a yellow amorphous solid (67 mg, 0.292 mmol, 82%). Rf = 0.20
The title compound was prepared from 3 (134 mg, 0.45 mmol)
and 1-ethynyl-4-methoxy-2-methyl-benzene (159 mg, 1.09 mmol)
according to the general procedure A, and isolated as a beige solid
(97 mg, 0.22 mmol, 49%). Rf = 0.63 (EtOAc/PE 1:1). Mp = 154–
(EtOAc/MeOH 9:1). ½a D20
ꢃ
ꢁ66.0 (c 1.00/DMSO). 1H NMR (DMSO-
d6 +
e
D2O, 400 MHz): d = 8.13 (s, 1H, H-50), 5.47 (d, 1H,
156 °C. ½a 2D0
ꢃ
ꢁ107.6 (c 1.0/CH2Cl2). 1H NMR (CDCl3, 400 MHz):
J = 9.2 Hz, H-1), 4.54 (s, 2H, CH2OH), 3.86 (dd, 1H, J = 10.8, 5.2 Hz,
H-5 eq), 3.78 (t, 1H, J = 9.2 Hz, H-2), 3.48–3.54 (m, 1H, H-4), 3.38
d = 7.79 (s, 1H, H-50), 7.68 (d, 1H, J = 8.7 Hz H-Ar), 6.80 (m, 2H, H-
Ar), 5.84 (d, 1H, J = 9.0 Hz, H-1), 5.45 (m, 2H, H-2, H-3), 5.18 (m,
1H, H-4), 4.31 (dd, 1H, J = 11.0, 5.7 Hz, H-5eq), 3.82 (s, 3H, PhOCH3),
3.62 (t, 1H, J = 11.0 Hz, H-5ax), 2.41 (s, 3H, PhCH3), 2.08, 2.05, 1.88
(3s, 9H, acetyl). 13C NMR (CDCl3, 100 MHz): d = 170.2, 170.1, 169.4
(3C, C@O), 159.9 (C-Ar), 147.8 (C-40), 137.6 (C-Ar), 130.6 (CH-Ar),
122.4 (C-Ar), 119.5 (C-50), 116.5 (CH-Ar), 111.8 (CH-Ar), 86.7 (C-
1), 72.4 (C-3), 70.7 (C-2), 68.8 (C-4), 65.9 (C-5), 55.6 (PhOCH3),
21.8 (PhCH3), 21.0, 20.5, 20.9 (3CH3, acetyl). ESI-MS (positive
mode) m/z: 448.2 [M+H]+, 470.2 [M+Na]+. HR-LSIMS-MS (positive
mode) m/z: calculated for C21H26N3O8 [M+H]+ 448.1714, found
448.1708.
(m, 2H, H-3, H-5ax). 13C NMR (DMSO-d6 +
e D2O, 100 MHz):
d = 148.9 (C-40), 123.1 (C-50), 89.1 (C-1), 78.0 (C-3), 73.0 (C-2),
70.1 (C-4), 69.4 (C-5), 55.9 (CH2OH). ESI-MS (positive mode) m/z:
254.1 [M+Na]+ HR-LSIMS-MS (positive mode) m/z: calculated for
.
C8H13N3O5 [M+Na]+ 254.0747, found 254.0747.
4.18. 1-(b-D
-Xylopyranosyl)-4-phenyl-1,2,3-triazole (5b)47
The title compound was prepared from 4b (137 mg, 0.34 mmol)
according to the general procedure B, and isolated as a pale yellow
solid (95 mg, 0.34 mmol, 99%). Rf = 0.33 (EtOAc/MeOH 9:1).
Mp = 163–170 °C. ½a D20
ꢃ
ꢁ40.1 (c 1.0/DMSO). 1H NMR (DMSO-
d6 +
e
D2O, 400 MHz): d = 8.84 (s, 1H, H-50), 7.91 (d, 2H,
4.15. 1-(2,3,4-Tri-O-acetyl-b-D-xylopyranosyl)-4-(2-naphthyl)-
J = 7.2 Hz, H-Ar), 7.49 (t, 2H, J = 7.6 Hz, H-Ar), 7.38 (t, 1H,
J = 7.6 Hz, H-Ar), 5.56 (d, 1H, J = 9.4 Hz, H-1), 3.90 (dd, 1H,
J = 10.8, 5.2 Hz, H-5 eq), 3.83 (t, 1H, J = 9.4 Hz, H-2), 3.80–3.86 (m,
1,2,3-triazole (4f)
The title compound was prepared from 3 (146 mg, 0.49 mmol)
and 2-ethynyl-naphthalene (138 mg, 0.46 mmol) according to the
general procedure A, and isolated as a white solid (202 mg,
1H, H-4), 3.39–3.47 (m, 2H, H-3, H-5ax). 13C NMR (DMSO-d6 +
e
D2O, 100 MHz): d = 147.3 (C-40), 131.6 (C-Ar), 129.9 (CH-Ar),
129.0 (CH-Ar), 126.2 (CH-Ar), 121.3 (C-50), 89.3 (C-1), 77.6 (C-3),
73.0 (C-2), 70.0 (C-4), 69.3 (C-5). ESI-MS (positive mode) m/z:
300.1 [M+Na]+, 576.9 [2M+Na]+. HR-LSIMS-MS (positive mode)
m/z: calculated for C13H15N3O4 [M+Na]+ 300.0955, found 300.0957.
0.45 mmol, 98%). Rf = 0.68 (EtOAc/PE 1:1). Mp = 245–249 °C. ½a D20
ꢃ
ꢁ130.6 (c 1.0/DMSO). 1H NMR (CDCl3, 400 MHz): d = 8.36 (s, 1H,
H-Ar), 8.10 (s, 1H, H-50), 7.86 (m, 4H, H-Ar), 7.50 (m, 2H, H-Ar),
5.88 (d, 1H, J = 8.4 Hz, H-1), 5.50 (t, 1H, J = 8.4 Hz, H-2), 5.46 (t,

D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
35
4.19. 1-(b-
D
-Xylopyranosyl)-4-(4-nitrophenyl)-1,2,3-triazole (5c)
Ar), 121.9 (C-50), 89.4 (C-1), 77.8 (C-3), 73.2 (C-2), 70.1 (C-4),
69.4 (C-5), ppm. ESI-MS (positive mode) m/z: 328.1 [M+H]+ HR-
.
The title compound was prepared from 4c (210 mg, 0.47 mmol)
according to the general procedure B, and isolated as a white solid
(150 mg, 0.47 mmol, 99%). Rf = 0.33 (EtOAc/MeOH 9:1). Mp = 197–
LSIMS-MS (positive mode) m/z: calculated for C17H17N3O4 [M+H]+
328.1292, found 328.1283.
198 °C. ½a 2D0
ꢃ
– 36.1 (c 1.0/DMSO). 1H NMR (DMSO-d6 +
e
D2O,
4.23. 1-(b-D-Xylopyranosyl)-4-(6-methoxy-2-naphthyl)-1,2,3-
triazole (5g)
400 MHz): d = 9.05 (s, 1H, H-50), 8.35 (d, 2H, J = 8.8 Hz, H-Ar),
8.16 (d, 2H, J = 8.8 Hz, H-Ar), 5.60 (d, 1H, J = 9.2 Hz, H-1), 3.91
(dd, 1H, J = 10.8, 5.2 Hz, H-5eq), 3.82 (t, 1H, J = 9.2 Hz, H-2), 3.52–
3.56 (m, 1H, H-4), 3.39–3.49 (m, 2H, H-3, H-5). 13C NMR (DMSO-
The title compound was prepared from 4g (165 mg, 0.34 mmol)
according to the general procedure B, and isolated as a pale beige
solid (121 mg, 0.34 mmol, 99%). Rf = 0.33 (EtOAc/MeOH 9:1).
d6 +
e
D2O, 100 MHz): d = 148.1 (C-40), 145.9 (C-Ar), 138.1 (C-Ar),
127.4 (2CH-Ar), 125.8 (2CH-Ar), 123.8 (C-50), 89.7 (C-1), 77.9 (C-
3), 73.4 (C-2), 70.3 (C-4), 69.6 (C-5). ESI-MS (negative mode) m/z:
357.1 [M+Cl]ꢁ. HR-LSIMS-MS (negative mode) m/z: calculated for
Mp = 240–245 °C. ½a D20
ꢃ
ꢁ25.6 (c 1.00/DMSO). 1H NMR (DMSO-
d6 +
e
D2O, 400 MHz): d = 8.91 (s, 1 H, H-50), 8.40 (s, 1H, H-Ar),
8.00 (d, 1H, J = 8.8 Hz, H-Ar), 7.90–7.93 (m, 2 H, H-Ar), 7.38 (d, 1
H, J = 2.4 Hz, H-Ar), 7.23 (dd, 1 H, J = 2.4 Hz, J = 8.8 Hz, H-Ar), 5.57
(d, 1 H, J = 9.0 Hz, H-1), 3.93 (s, 3H, PhOCH3), 3.88–3.95 (m, 1 H,
H-5eq), 3.86 (t, 1 H, J = 9.0 Hz, H-2), 3.25–3.60 (m, 3 H, H-3, H-4,
C
13H14N4O6 [M+Cl]ꢁ 357.0607, found 357.0607.
4.20. 1-(b-D-Xylopyranosyl)-4-(4-methylphenyl)-1,2,3-triazole
(5d)
H-5ax). 13C NMR (DMSO-d6 +
e D2O, 100 MHz): d = 158.4 (C-Ar),
147.5 (C-40), 134.9 (C-Ar), 130.5 (CH-Ar), 129.5 (C-Ar), 128.4 (C-
Ar), 126.8 (CH-Ar), 125.1 (CH-Ar), 124.4 (CH-Ar), 121.2 (C-50),
120.1 (CH-Ar), 107.0 (CH-Ar), 89.3 (C-1), 77.8 (C-3), 73.2 (C-2),
70.1 (C-4), 69.3 (C-5), 56.2 (PhOCH3). ESI-MS (positive mode) m/
z: 380.1 [M+Na]+, 737.0 [2 M+Na]+. HR-LSIMS-MS (positive mode)
m/z: calculated for C18H19N3O5 [M+Na]+ 380.1217, found 380.1217.
The title compound was prepared from 4d (146 mg, 0.35 mmol)
according to the general procedure B, and isolated as a pale beige
solid (101 mg, 0.35 mmol, 99%). Rf = 0.30 (EtOAc/MeOH 9:1).
Mp = 178–181 °C.
½
a 2D0
ꢃ
–
45.3 (c 1.0/DMSO). 1H NMR1H NMR
(DMSO-d6 +
e
D2O, 400 MHz): 8.77 (s, 1H, H-50), 7.79 (d, 2H,
J = 8.0 Hz H-Ar), 7.30 (d, 2H, J = 8.0 Hz, H-Ar), 5.54 (d, 1H,
J = 9.4 Hz, H-1), 3.90 (dd, 1H, J = 10.8, 5.2 Hz, H-5 eq), 3.82 (t, 1H,
J = 9.4 Hz, H-2), 3.51–3.54 (m, 1H, H-4), 3.38–3.50 (m, 2H, H-3,
4.24. 2,3,4-Tri-O-acetyl-5-thio-b-D
-xylopyranosyl azide (7)54
H-5ax), 2.36 (s, 3H, PhCH3). 13C NMR (DMSO-d6 +
e
D2O,
To a solution of sodium azide (1.83 g, 28.15 mmol, 2 equiv) in
DMSO (40 mL) was added 2,3,4-tri-O-acetyl-5-thio- -xylopyr-
100 MHz): d = 147.4 (C-40), 138.4 (C-Ar), 130.5 (C-50), 128.8 (C-
Ar), 126.1 (2CH-Ar), 120.9 (2CH-Ar), 89.3 (C-1), 77.8 (C-3), 73.0
(C-2), 70.0 (C-4), 69.3 (C-5), 21.9 (PhCH3). ESI-MS (positive mode)
m/z: 314.1 [M+Na]+, 604.9 [2M+Na]+. HR-LSIMS-MS (positive
mode) m/z: calculated for C14H17N3O4 [M+Na]+ 314.1111, found
314.1109.
a-D
anosyl bromide 653 (5.00 g, 14.08 mmol, 1 equiv). The reaction
was stirred at rt for 2 h, diluted with Et2O (150 mL), and washed
with water (100 mL). The aqueous layer was extracted with Et2O
(3 ꢂ 50 mL). The organic layers were combined, washed with
water (4 ꢂ 150 mL), dried (MgSO4), filtered, and concentrated in
vacuo. The crude product was solubilized in a minimum of Et2O,
precipitated with Pet. Ether and filtered to afford azido 2,3,4-tri-
4.21. 1-(b-D-Xylopyranosyl)-4-(4-methoxy-2-methylphenyl)-
1,2,3-triazole (5e)
O-acetyl-5-thio-b-D-xylopyranose 7 as a white powder (3.84 g,
12.11 mmol, 86%). 1H NMR (CDCl3, 300 MHz): d = 5.03–5.18 (m,
3H, H-2, H-3, H-4), 4.48 (d, 1H, J = 9.2 Hz, H-1), 2.95 (dd, 1H,
J = 13.7, 3.7, H-5e), 2.71 (dd, 1H, J = 13.7, 10.5, H-5a), 2.09, 2.03,
2.03 (3s, 9H, acetyl).
The title compound was prepared from 4e (100 mg,
0.223 mmol) according to the general procedure B, and isolated
as a beige solid (72 mg, 0.223 mmol, 99%). Rf = 0.37 (EtOAc/MeOH
9:1). Mp = 158–165 °C. ½a D20
ꢃ
– 33.9 (c 1.0/DMSO). 1H NMR (DMSO-
d6 +
e
D2O, 400 MHz): d = 8.48 (s, 1H, H-50), 7.68 (d, 1H, J = 8.4 Hz
4.25. 2,3,4-Tri-O-acetyl-5-thio-b-
oxide (8-S)
D-xylopyranosyl azide (S)-S-
H-Ar), 6.89 (m, 2H, H-Ar), 5.54 (d, 1H, J = 9.6 Hz, H-1), 3.87–3.92
(m, 2H, H-2, H-5 eq), 3.81 (s, 3H, PhOCH3), 3.38–3.53 (m, 3H, H-
3, H-4, H-5ax), 2.44 (s, 3H, PhCH3). 13C NMR (DMSO-d6 +
e
D2O,
The title compound was prepared from 7 according to the gen-
eral procedure E, and isolated as a white powder. Rf = 0.27 (PE/
100 MHz): d = 159.9 (C-Ar), 146.5 (C-40), 137.8 (C-Ar), 130.7 (CH-
Ar), 123.5 (C-Ar), 122.5 (C-50), 117.1 (CH-Ar), 112.6 (CH-Ar), 89.3
(C-1), 77.9 (C-3), 72.8 (C-2), 70.0 (C-4), 69.3 (C-5), 56.1 (PhOCH3),
22.3 (PhCH3). ESI-MS (positive mode) m/z: 344.1 [M+Na]+, 665.0
[2M+Na]+, 985.8 [3M+Na]+. HR-LSIMS-MS (positive mode) m/z: cal-
culated for C15H19N3O5 [M+Na]+ 344.1217, found 344.1213.
EtOAc 1:1). Mp = 135–136 °C (CH2Cl2/PE). ½a D20
ꢁ62 (c 1/CH2Cl2).
ꢃ
1H NMR (CDCl3, 400 MHz): d = 5.34 (pdd, 1H, J = 9.8 Hz, H-3),
5.05 (ddd, 1H, J = 12.5, 10.0, 3.8 Hz, H-4), 5.00 (dd, 1H, J = 10.9,
9.9 Hz, H-2), 4.48 (d, 1H, J = 11.1 Hz, H-1), 3.70 (dd, 1H, J = 12.2,
3.7 Hz, H-5e), 3.06 (pdd, 1H, J = 12.2 Hz, H-5a), 2.09, 2.04, 2.00
(3s, 9H, acetyl). 13C NMR (CDCl3, 100 MHz): d = 169.4, 169.3,
168.9 (3C, acetyl), 83.1 (C-2), 72.3 (C-3), 66.9 (C-4), 64.4 (C-1),
50.9 (C-5), 20.6, 20.5, 20.4 (3CH3, acetyl). HR-LSIMS-MS (positive
mode) m/z: calculated for C11H16N3O7S [M+H]+ 334.0709, found
334.0707.
4.22. 1-(b-D-Xylopyranosyl)-4-(2-naphthyl)-1,2,3-triazole (5f)
The title compound was prepared from 4f (178 mg,
0.393 mmol) according to the general procedure B, and isolated
as a pale beige solid (123 mg, 0.375 mmol, 95%). Rf = 0.66 (EtOAc/
MeOH 9:1). Mp = 207–210 °C. ½a D20
ꢃ
ꢁ44.9 (c 1.0/DMSO). 1H NMR
4.26. 2,3,4-Tri-O-acetyl-5-thio-b-
oxide (8-R)
D-xylopyranosyl azide (R)-S-
(DMSO-d6 +
e
D2O, 400 MHz): d = 8.96 (s, 1 H, H-50), 8.47 (s, 1H,
H-Ar), 7.95–8.05 (m, 4H, H-Ar), 7.57 (m, 2H, H-Ar), 5.59 (d, 1H,
J = 9.0 Hz, H-1), 3.92 (dd, 1H, J = 10.8, 4.8 Hz, H-5 eq), 3.86 (t, 1H,
J = 9.0 Hz, H-2), 3.52–3.60 (m, 1H, H-4), 3.43–3.49 (m, 2H, H-3,
The title compound was prepared from 7 according to the gen-
eral procedure E, and isolated as a white powder. Rf = 0.22 (PE/
H-5ax). 13C NMR (DMSO-d6 +
e
D2O, 100 MHz): d = 147.5 (C-40),
EtOAc 1:1). Mp = 129–130 °C (CH2Cl2/PE). ½a D20
ꢁ47 (c 0.50/CH2Cl2).
ꢃ
134.3 (C-Ar), 133.7 (C-Ar), 129.7 (CH-Ar), 129.1 (CH-Ar), 129.1
(CH-Ar), 128.8 (CH-Ar), 127.4 (CH-Ar), 124.7 (CH-Ar), 124.7 (CH-
1H NMR (CDCl3, 300 MHz): d = 5.78 (dd, 1H, J = 10.3, 9.5 Hz, H-2),
5.70 (ddd, 1H, J = 11.5, 9.6, 4.0 Hz, H-4), 5.35 (pdd, 1H, J = 9.5 Hz,

36
D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
H-3), 4.09 (d, 1H, J = 10.3 Hz, H-1), 3.63 (dd, 1H, J = 14.1, 4.0 Hz, H-
5e), 2.65 (dd, 1H, J = 14.1, 11.5 Hz, H-5a), 2.12, 2.07, 2.05 (3s, 9H,
acetyl). HR-LSIMS-MS (positive mode) m/z: calculated for
Ar), 6.24 (d, 1H, J = 10.2 Hz, H-1), 5.70 (dd, 1H, J = 10.0, 9.5 Hz, H-
2), 5.39 (pdd, 1H, J = 9.6 Hz, H-3), 5.20 (ddd, 1H, J = 10.8, 9.9,
4.5 Hz, H-4), 3.28 (dd, 1H, J = 13.5, 10.8 Hz, H-5a), 3.11 (dd, 1H,
J = 13.5, 4.5, H-5e), 2.35 (s, 3H, methyl), 2.03, 1.99, 1.76 (3s, 9H,
acetyl). 13C NMR (DMSO-d6, 75 MHz): d = 169.3, 169.1, 168.4 (3C,
C@O), 146.8 (C-40), 137.5 (C-Ar), 129.4 (2CH-Ar), 127.2 (C-Ar),
125.1 (2CH-Ar), 120.5 (C-50), 73.7 (C-2), 72.1 (C-3), 71.5 (C-4),
58.8 (C-1), 28.1 (C-5), 20.7 (CH3, methyl), 20.5, 20.1, 19.7 (3CH3,
acetyl). HR-LSIMS-MS (positive mode) m/z: calculated for
C
11H16N3O7S [M+H]+ 334.0709, found 334.0712.
4.27. 1-(2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl)-4-
(acetoxymethyl)-1,2,3-triazole (9a)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (243 mg,
0.58 mmol 93%). Rf = 0.11 (PE/EtOAc 6:4). Mp = 158–159 °C
C
20H23N3NaO6S [M+Na]+ 456.1205, found 456.1205.
(MeOH). ½a 2D0
ꢃ
+21 (c 1.45/DMSO). 1H NMR (CDCl3, 400 MHz)
4.31. 1-[2,3,4-Tri-O-acetyl-5-thio-b- -xylopyranosyl]-4-(2-
D
d = 7.79 (br s, 1H, H-50), 5.77 (d, 1H, J = 10.2 Hz, H-1), 5.52 (pdd,
1H, J = 9.6 Hz, H-2), 5.24 (pdd, 1H, J = 9.4 Hz, H-3), 5.14–5.19 (m,
1H, H-4), 5.17 (s, 2H, CH2OAc), 3.07 (dd, 1H, J = 13.8, 4.2 Hz, H-
5e), 2.91 (dd, 1H, J = 13.8, 10.3 Hz, H-5a), 2.07, 2.06, 2.02, 1.80
(4s, 12H, acetyl). 13C NMR (CDCl3, 100 MHz) d = 170.8, 169.8,
169.5, 169.0 (4C, C@O), 73.9 (C-2), 72.7 (C-3), 72.0 (C-4), 60.9 (C-
1), 57.5 (CH2OAc), 29.6 (C-5), 20.9, 20.8, 20.6, 20.1 (4CH3, acetyl).
HR-LSIMS-MS (positive mode) m/z: calculated for C16H21NaN3O8S
[M+Na]+ 438.0942, found 438.0946.
methyl-4-methoxyphenyl)-1,2,3-triazole (9e)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (280 mg,
0.60 mmol, 96%). Rf = 0.44 (PE/EtOAc 6:4). Mp = 189–190 °C
(MeOH). ½a 2D0
ꢃ
+19 (c 1/DMSO). 1H NMR (DMSO-d6, 300 MHz MHz):
d 8.45 (s, 1H, H-50), 7.58 (d, 1H, J = 8.1 Hz, H-Ar), 6.84–6.87 (m, 2H,
H-Ar), 6.38 (d, 1H, J = 9.9 Hz, H-1), 5.68 (pdd, 1H, J = 9.8 Hz, H-2),
5.39 (pdd, 1H, J = 9.6 Hz, H-3), 5.13 (pddd, 1H, J = 10.8, 4.3 Hz, H-
4), 3.77 (s, 3H, OCH3), 3.27 (pdd, 1H, J = 13.1, 11.1 Hz, H-5a), 3.03
(dd, 1H, J = 13.2, 4.3 Hz, H-5e), 2.35 (s, 3H, methyl), 2.03, 1.99,
1.76 (3s, 9H, acetyl). 13C NMR (DMSO-d6, 75 MHz): d 169.3,
169.1, 168.3 (3C, C=O), 158.9 (C-Ar), 147.1 (C-Ar), 145.9 (C-40),
136.8 (C-Ar), 129.6 (CH-Ar), 121.9 (C-50), 115.9 (CH-Ar), 111.5
(CH-Ar), 73.7 (C-2), 72.2, (C-3), 71.5 (C-4), 58.8 (C-1), 55.0
(OCH3), 28.1 (C-5), 20.9 (CH3, methyl), 20.5, 20.1, 19.7 (3CH3, acet-
yl). HR-LSIMS-MS (positive mode) m/z: calculated for
4.28. 1-[2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl]-4-phenyl-
1,2,3-triazole (9b)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (253 mg,
0.60 mmol, 96%). Rf = 0.61 (PE/EtOAc 1:1). Mp >250 °C (MeOH).
½
a 2D0 +11 (c 0.94/DMSO). 1H NMR (CDCl3, 300 MHz): d = 7.92 (s,
ꢃ
1H, H-50), 7.80–7.83 (m, 2H, H-Ar), 7.33–7.46 (m, 3H, H-Ar), 5.85
(d, 1H, J = 10.2 Hz, H-1), 5.63 (dd, 1H, J = 10.2, 9.1 Hz, H-2), 5.17–
5.31 (m, 2H, H-3, H-4), 3.10 (dd, 1H, J = 13.6, 4.3 Hz, H-5e), 2.94
(dd, 1H, J = 13.8, 10.5 Hz, H-5a), 2.08, 2.04, 1.82 (3s, 9H, acetyl).
13C NMR (CDCl3, 75 MHz): d = 169.7, 169.4, 169.0 (3C, C@O),
148.5 (C-40), 129.8 (C-Ar), 128.9 (2CH-Ar), 128.6 (CH-Ar), 125.9
(2CH-Ar), 118.3 (C-50), 73.6 (C-2), 72.7 (C-3), 71.9 (C-4), 60.7 (C-
1), 29.6 (C-5), 20.8, 20.5, 20.1 (3CH3, acetyl). HR-LSIMS-MS (posi-
tive mode) m/z: calculated for C19H21N3NaO8S [M+Na]+ 442.1049,
found 442.1048.
C
21H25N3NaO7S [M+Na]+ 486.1311, found 486.1311.
4.32. 1-(2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl)-4-(2-
naphthyl)-1,2,3-triazole (9f)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (280 mg,
0.59 mmol, 95%). Rf = 0.69 (PE/EtOAc 1:1). Mp >250 °C (MeOH).
½
a 2D0 +22 (c 1.08/DMSO). 1H NMR (400 MHz, CDCl3) d = 8.34 (s,
ꢃ
1H, H-50), 8.04 (s, 1H, H-Ar), 7.83–7.90 (m, 4H, H-Ar), 7.46–7.53
(m, 2H, H-Ar), 5.89 (d, 1H, J = 10.3 Hz, H-1), 5.67 (dd, 1H, J = 10.2,
9.2 Hz, H-2), 5.29 (pdd, 1H, J = 9.4 Hz, H-3), 5.23 (pddd, 1H,
J = 10.1, 4.3 Hz, H-4), 3.10 (dd, 1H, J = 13.8, 4.3 Hz, H-5e), 2.96
(dd, 1H, J = 13.8, 10.5 Hz, H-5a), 2.08, 2.05, 1.83 (3s, 9H, acetyl).
13C NMR (100 MHz MHz, CDCl3) d = 169.6, 169.6, 169.3 (3C,
C@O), 148.8 (C-40), 133.6 (C-Ar), 133.5 (C-Ar), 128.8 (CH-Ar),
128.4 (CH-Ar), 127.9 (CH-Ar), 127.3 (C-Ar), 126.7 (CH-Ar), 126.5
(CH-Ar), 124.9 (C-50), 123.9 (CH-Ar), 118.7 (CH-Ar), 73.8 (C-2),
72.9 (C-3), 72.1 (C-4), 60.9 (C-1), 29.7 (C-5), 20.9, 20.6, 20.2
(3CH3, acetyl). HR-LSIMS-MS (positive mode) m/z: calculated for
C23H23N3NaO6S [M+Na]+ 492.1200, found 492.1200.
4.29. 1-[2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl]-4-(4-
nitrophenyl)-1,2,3-triazole (9c)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a pale yellow powder (0.59 mmol,
275 mg, 94%). Rf = 0.53 (PE/EtOAc 1:1). Mp = 244–245 °C (MeOH).
½
a 2D0 +15 (c 1/DMSO). 1H NMR (DMSO-d6, 300 MHz): d = 9.13 (s,
ꢃ
1H, H-50), 8.33 (d, 2H, J = 8.9 Hz H-Ar), 8.14 (d, 2H, J = 8.9 Hz, H-
Ar), 6.45 (d, 1H, J = 10.0 Hz, H-1), 5.59 (pdd, 1H, J = 9.7 Hz, H-2),
5.41 (pdd, 1H, J = 9.6 Hz, H-3), 5.21 (pddd, 1H, J = 10.3, 4.4 Hz, H-
4), 3.29 (dd, 1H, J = 13.2, 11.1 Hz, H-5a), 3.07 (dd, 1H, J = 13.3,
4.4 Hz, H-5e), 2.08, 2.04, 1.84 (3s, 9H, acetyl). 13C NMR (DMSO-
d6, 75 MHz): d = 169.3, 169.1, 168.4 (3C, C@O), 146.8 (C-Ar),
144.9 (C-40), 136.2 (C-Ar), 126.1 (2CH-Ar), 124.3 (2CH-Ar), 123.2
(C-50), 73.7 (C-2), 72.0 (C-3), 71.5 (C-4), 58.9 (C-1), 28.1 (C-5),
20.5, 20.1, 19.7 (3CH3, acetyl). HR-LSIMS-MS (positive mode) m/z:
calculated for C19H20N4NaO8S [M+H]+ 487.0900, found 487.0900.
4.33. 1-[2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl]-4-(6-
methoxy-2-naphthyl)-1,2,3-triazole (9g)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (308 mg,
0.62 mmol, 98%). Rf = 0.61 (PE/EtOAc 1:1). Mp >250 °C (MeOH).
½
a 2D0 +26 (c 0.63/DMSO). 1H NMR (DMSO-d6, 300 MHz): d = 8.87
ꢃ
4.30. 1-[2,3,4-Tri-O-acetyl-5-thio-b-
D
-xylopyranosyl]-4-(4-
(s, 1H, H-50), 8.35 (s, 1H, H-Ar), 7.95 (dd, 1H, J = 8.6, 1.3 Hz, H-
Ar), 7.88 (d, 2H, J =9.7 Hz, H-Ar), 7.34 (d, 1H, J = 2.2 Hz, H-Ar),
7.20 (dd, 1H, J = 8.9, 2.4 Hz, H-Ar), 6.42 (d, 1H, J = 10.0 Hz, H-1),
5.62 (pdd, 1H, J = 9.7 Hz, H-2), 5.42 (pdd, 1H, J = 9.6 Hz, H-3), 5.12
(pddd, 1H, J = 10.7, 4.3, H-4), 3.89 (s, 3H, OCH3), 3.30 (dd, 1H,
J = 13.1, 11.2, H-5a), 3.06 (dd, 1H, J = 13.2, 4.3 H-5e), 2.04, 1.99,
1.77 (3s, 9H, acetyl). 13C NMR (DMSO-d6, 75 MHz MHz):
d = 169.3, 169.1, 168.4 (3C, C@O), 157.5 (C-Ar), 147.0 (C-40), 134.0
methylphenyl)-1,2,3-triazole (9d)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (249 mg,
0.57 mmol, 90%). Rf = 0.80 (PE/EtOAc 1:1). Mp >250 °C (MeOH).
½
a 2D0 +14 (c 1/DMSO). 1H NMR ((CD3)2CO, 300 MHz): d = 8.48 (s,
ꢃ
1H, H-50), 7.78 (d, 2H, J = 8.2 Hz, H-Ar) 7.25 (d, 2H, J = 7.9 Hz, H-

D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
37
(C-Ar), 129.5 (CH-Ar), 128.3 (C-Ar), 127.3 (CH-Ar), 125.1 (C-Ar),
123.9 (CH-Ar), 123.6 (CH-Ar), 120.8 (C-50), 119.1 (CH-Ar), 105.9
(CH-Ar), 73.7 (C-2), 72.1 (C-3), 71.6 (C-4), 58.8 (C-1), 55.1 (OCH3),
28.1 (C-5), 20.5, 20.1, 19.7 (3CH3, acetyl). HR-LSIMS-MS (positive
mode) m/z: calculated for C24H25N3NaO7S [M+Na]+ 522.1311,
found 522.1312.
4.37. 5-Thio-b-D-xylopyranosyl-4-hydroxymethyl-1,2,3-triazole
(10a)
The title compound was prepared from 9a according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.21
(CH2Cl2/MeOH 9:1). Mp = 171–172 °C (MeOH/Et2O). ½a D20
ꢃ
+42 (c
1
0.81/DMSO). H NMR (CD3OD, 400 MHz): d = 8.01 (s, 1H, H-50),
5.57 (d, 1H, J = 10.0 Hz, H-1), 4.68 (s, 2H, CH2OH), 4.03 (dd, 1H,
J = 9.9, 9.0 Hz, H-2), 3.77 (ddd, 1H, J = 10.7, 9.1, 4.6, H-4), 3.28–
3.32 (m, 1H, H-3), 2.87 (dd, 1H, J = 13.6, 107 Hz, H-5a), 2.78 (dd,
1H, J = 13.6, 4.6 Hz, H-5e). 13C NMR (CD3OD, 100 MHz): d = 149.0
(C-40), 123.9 (C-50), 79.5 (C-3), 77.5 (C-2), 74.2 (C-4), 64.1 (C-1),
56.5 (CH2OH), 33.2 (C-5). HR-LSIMS-MS (positive mode) m/z: cal-
culated for C8H13N3NaO4S [M+Na]+ 270.0519, found 270.0519.
4.34. 1-[2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl]-4-(4-
methoxyphenyl)-1,2,3-triazole (9h)
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (229 mg,
0.51 mmol, 81%). Rf = 0.60 (PE/EtOAc 1:1). Mp = 249–250 °C
(MeOH). ½a 2D0
ꢃ
+17 (c 1/DMSO). 1H NMR (DMSO-d6, 300 MHz):
d = 8.69 (s, 1H, H-50), 7.78 (d, 2H, J = 8.8 Hz, H-Ar), 7.00 (d, 2H,
J = 8.8 Hz, H-Ar), 6.37 (d, 1H, J = 10.0 Hz, H-1), 5.63 (pdd, 1H,
J = 9.7 Hz, H-2), 5.39 (pdd, 1H, J = 9.6 Hz, H-3), 5.10 (pddd, 1H,
J = 10.3, 4.2 Hz, H-4), 3.79 (s, 3H, OCH3), 3.27 (dd, 1H, J = 13.3,
11.4 Hz, H-5a), 2.93 (dd, 1H, J = 13.2, 4.5 Hz, H-5e), 2.03, 1.98,
1.95 (3s, 9H, acetyl). 13C NMR (DMSO-d6, 75 MHz): d = 169.3,
169.1, 168.3 (3C, C@O), 159.2 (C-Ar), 146.6 (C-40), 126.6 (2CH-
Ar), 122.5 (C-Ar), 119.9 (C-50), 114.2 (2CH-Ar), 73.6 (C-2), 72.1
(C-3), 71.5 (C-4), 58.8 (C-1), 55.1 (OCH3), 28.1 (C5), 20.5, 20.1,
19.7 (3CH3, acetyl). HR-LSIMS-MS (positive mode) m/z: calculated
for C20H23N3NaO7S [M+Na]+ 472.1154, found 472.1156.
4.38. 5-Thio-b-D-xylopyranosyl-4-phenyl-1,2,3-triazole (10b)
The title compound was prepared from 9b according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.30
(CH2Cl2/MeOH 9:1). Mp = 219–220 °C (MeOH). ½a D20
ꢃ
+14 (c 1/
e D2O, 400 MHz): d = 8.68 (s, 1H, H-
DMSO). 1H NMR (DMSO-d6 +
50), 7.87 (m, 2H, H-Ar), 7.42–7.46 (m, 2H, H-Ar), 73.31–7.35 (m,
1H, H-Ar), 5.63 (d, 1H, J = 10.0 Hz, H-1), 3.92 (dd, 1H, J = 9.9,
8.9 Hz, H-2), 3.58 (ddd, 1H, J = 10.8, 9.1, 4.5 Hz, H-4), 3.21 (pdd,
1H, J = 8.9 Hz, H-3), 2.82 (dd, 1H, J = 13.4, 10.8 Hz, H-5a), 2.71
(dd, 1H, J = 13.4, 4.5 Hz, H-5e). 13C NMR (DMSO-d6 +
e D2O,
4.35. 1-[2,3,4-Tri-O-acetyl-5-thio-b-
(cyclohexyl)-1,2,3-triazole (9i)
D
-xylopyranosyl]-4-
100 MHz): d = 146.8 (C-Ar), 129.5 (CH-Ar), 129.5 (CH-Ar), 128.7
(CH-Ar), 125.7 (2CH-Ar), 121.5 (C-50), 77.7 (C-3), 75.8 (C-2), 72.8
(C-4), 62.4 (C-1), 32.0 (C-5). HR-CI-MS (positive mode) m/z: calcu-
lated for C13H16N3O3S [M+H]+ 294.0912, found 294.0913.
The title compound was prepared from 7 according to the gen-
eral procedure C, and isolated as a white powder (241 mg,
0.57 mmol, 90%). Rf = 0.77 (PE/EtOAc 1:1). Mp = 209–210 °C
4.39. 5-Thio-b-D-xylopyranosyl-4-(4-nitrophenyl)-1,2,3-triazole
(10c)
(MeOH).
½
a 2D0
ꢃ
+39 (c 1/DMSO). 1H NMR (CDCl3, 300 MHz):
d = 7.39 (s, 1H, H-50), 5.75 (d, 1H, J = 10.3 Hz, H-1), 5.53 (pdd, 1H,
J = 9.7 Hz, H-2), 5.23 (pdd, 1H, J = 9.7 Hz, H-3), 5.16 (pddd, 1H,
J = 9.7, 4.4 Hz, H-4), 3.05 (dd, 1H, J = 13.6, 4.2, H-5e), 2.89 (dd,
1H, J = 13.7, 10.4, H-5a), 2.69–2.78 (m, 1H, cyclohexyl), 2.06, 2.02,
1.79 (3s, 9H, acetyl), 1.99–2.04 (m, 2H, cyclohexyl), 1.60–1.78 (m,
4H, cyclohexyl), 1.23–1.45 (m, 4H, cyclohexyl). 13C NMR (CDCl3,
75 MHz): d = 169.7, 169.4, 168.9 (3C, C@O), 154.5 (C-40), 118.1
(C-50), 73.7 (C-2), 72.7 (C-3), 72.0 (C-4), 60.5 (C-1), 35.2 (CH, cyclo-
hexyl), 32.7 (2CH2, cyclohexyl), 29.5 (C5), 26.0 (2CH2, cyclohexyl),
25.9 (CH2, cyclohexyl), 20.7, 20.4, 20.0 (CH3, acetyl). HR-LSIMS-MS
The title compound was prepared from 9c according to the gen-
eral procedure D, and isolated as a pale yellow powder (99%).
Rf = 0.29 (CH2Cl2/MeOH 9:1). Mp = 131–132 °C (MeOH). ½a D20
ꢃ
+16
(c 1.25/DMSO). 1H NMR (DMSO-d6 +
e D2O, 400 MHz, 45°C):
d = 8.92 (s, 1H, H-50), 8.30 (d, 2H, J = 8.9 Hz, 2H-Ar), 8.13 (d, 2H,
J = 8.9 Hz, 2H-Ar), 5.66 (d, 1H, J = 10.0 Hz, H-1), 3.94 (pdd, 1H,
J = 9.3 Hz, H-2), 3.61 (ddd, 1H, J = 10.4, 9.0, 4.4 Hz, H-4), 3.24
(pdd, 1H, J = 8.8 Hz, H-3), 2.83 (dd, 1H, J = 13.3, 10.7 Hz, H-5a),
2.74 (dd, 1H, J = 13.4, 4.5 Hz, H-5e). 13C NMR (DMSO-d6 +
e D2O,
(positive mode) m/z: calculated for
448.1518, found 448.1517.
C
19H27N3NaO6S [M+Na]+
400 MHz, 45°C): d = 146.7 (C-Ar), 144.3 (C-40), 136.9 (C-Ar), 126.0
(2CH-Ar), 124.3 (2CH-Ar), 123.1 (C-50), 77.5 (C-3), 75.6 (C-2), 72.5
(C-4), 62.4 (C-1), 31.8 (C-5). HR-CI-MS (positive mode) m/z: calcu-
lated for C13H15N4O5S [M+H]+ 339.0763, found 339.0762.
4.36. 1-[2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl]-4-
(cyclohex-1-enyl)-1,2,3-triazole (9j)
4.40. 5-Thio-b-D-xylopyranosyl-4-(4-methylphenyl)-1,2,3-
The title compound was prepared from 7 according to the gen-
triazole (10d)
eral procedure C, and isolated as a white powder (238 mg,
0.56 mmol 89%). Mp = 194–195 °C (MeOH). ½a D20
ꢃ
+31 (c 1/DMSO).
The title compound was prepared from 9d according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.31
1H NMR (CDCl3, 300 MHz): d 7.52 (s, 1H, H-50), 6.54 (m, 1H, CH-
sp2), 5.78 (d, 1H, J = 10.3 Hz, H-1), 5.56 (pdd, 1H, J = 9.6 Hz, H-2),
5.23 (pdd, 1H, J = 9.1 Hz, H-3), 5.17 (pddd, 1H, J = 9.8, 4.3 Hz, H-
4), 3.03 (dd, 1H, J = 13.9, 4.2 Hz, H-5e), 2.90 (dd, 1H, J = 13.7, 10.3,
H-5a), 2.30–2.34 (m, 2H, cyclohexene), 2.17–2.20 (m, 2H, cyclohex-
ene), 2.06, 2.02, 1.81 (3s, 9H, acetyl), 1.71–1.79 (m, 2H, cyclohex-
ene), 1.63–1.69 (m, 2H, cyclohexene). 13C NMR (CDCl3, 75 MHz):
d = 169.7, 169.4, 169.0 (3C, C@O), 126.7 (C-40), 126.0 (CH, cyclohex-
ene), 116.8 (C-50), 77.2 (C, cyclohexene), 73.5 (C-2), 72.7 (C-3), 71.9
(C-4), 60.5 (C-1), 29.5 (C-5), 26.2, 25.2, 22.3, 22.1 (4CH2, cyclohex-
ene), 20.7, 20.4, 20.1 (3CH3, acetyl). HR-LSIMS-MS (positive mode)
(CH2Cl2/MeOH 9:1). Mp = 235–236 °C (MeOH). ½a D20
ꢃ
+29 (c 1.07/
e D2O, 400 MHz): d = 8.57 (s, 1H, H-
DMSO). 1H NMR (DMSO-d6 +
50), 7.72 (d, 2H, J = 8.1 Hz, H-Ar), 7.25 (d, 2H, J = 8.0 Hz, H-Ar),
5.60 (d, 1H, J = 10.0 Hz, H-1), 3.90 (dd, 1H, J = 9.9, 8.9 Hz, H-2),
3.58 (ddd, 1H, J = 10.6, 9.0, 4.5 Hz, H-4), 3.19 (pdd, 1H, J = 8.9 Hz,
H-3), 2.80 (dd, 1H, J = 13.4, 10.8 Hz, H-5a), 2.71 (dd, 1H, J = 13.4,
4.5 Hz, H-5e), 2.30 (s, 3H, methyl). 13C NMR (DMSO-d6 +
e D2O,
100 MHz): d = 146.7 (C-40), 137.9 (C-Ar), 129.9 (2CH-Ar), 127.8
(C-Ar), 125.5 (2CH-Ar), 120.9 (C-50), 77.8 (C-3), 75.8 (C-2), 72.8
(C-4), 62.5 (C-1), 32.1 (C-5), 21.1 (C-methyl). HR-CI-MS (positive
mode) m/z: calculated for C14H18N3O3S [M+H]+ 308.1070, found
308.1070.
m/z: calculated for
C
19H25N3NaO6S [M+Na]+ 446.1362, found
446.1362.

38
D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
4.41. 5-Thio-b-
1,2,3-triazole (10e)
D
-xylopyranosyl-4-(2-methyl-4-methoxyphenyl)-
H-3), 2.70–2.85 (m, 2H, H-5a, H-5e). 13C NMR (DMSO-d6 +
e D2O,
100 MHz): d = 160.2 (C-Ar), 147.5 (C-40), 127.8 (2CH-Ar), 123.3
(C-Ar), 121.3 (C-50), 115.5 (2CH-Ar), 78.3 (C-3), 76.4 (C-2), 73.3
(C-4), 63.1 (C-1), 56.1 (CH3-methoxy), 32.5 (C-5). HR-CI-MS (posi-
tive mode) m/z: calculated for C14H18N3O4S [M+H]+ 324.1018,
found 324.1017.
The title compound was prepared from 9e according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.30
(CH2Cl2/MeOH 9:1). Mp = 199–200 °C (MeOH). ½a D20
ꢃ
+37 (c 1.10/
e D2O, 400 MHz): d = 8.22 (s, 1H, H-
DMSO). 1H NMR (DMSO-d6 +
50), 7.56 (d, 1H, J = 8.2 Hz, H-Ar), 6.81–6.84 (m, 2H, H-Ar), 5.56 (d,
1H, 10.0 Hz, H-1), 3.94 (pdd, 1H, J = 9.4 Hz, H-2), 3.72 (s, 3H,
OCH3), 3.62 (pddd, 1H, J = 9.5, 4.9 Hz, H-4), 3.20 (pdd, 1H,
J = 8.9 Hz, H-3), 2.68–2.83 (m, 2H, H-5a, H-5e), 2.32 (s, 3H, methyl).
4.45. 5-Thio-b-D-xylopyranosyl-4-cyclohexyl-1,2,3-triazole (10i)
The title compound was prepared from 9i according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.32
13C NMR (DMSO-d6 +
e
D2O, 100 MHz): d = 159.9 (C-Ar), 146.5 (C-
(CH2Cl2/MeOH 9:1). Mp = 205–206 °C (MeOH). ½a D20
ꢃ
+40 (c 1.03/
40), 138.0 (C-Ar), 130.8 (CH-Ar), 123.5 (C-50), 122.8 (C-Ar), 117.0
(CH-Ar), 112.7 (CH-Ar), 78.3 (C-3), 76.4 (C-2), 73.3 (C-4), 63.1 (C-
1), 56.0 (CH3-methoxy), 32.5 (C-5), 21.8 (CH3-methyl). HR-CI-MS
DMSO). 1H NMR (DMSO-d6 +
e D2O, 400 MHz): d = 7.87 (s, 1H, H-
50), 5.51 (d, 1H, J = 10.0 Hz, H-1), 3.85 (dd, 1H, J = 9.8, 9.0 Hz, H-
2), 3.54 (ddd, 1H, J = 10.3, 9.1, 4.5 Hz, H-4), 3.13 (pdd, 1H,
J = 8.9 Hz, H-3), 2.75 (dd, 1H, J = 13.4, 10.8, H-5a), 2.66 (dd, 1H,
J = 13.4, 4.5 Hz, H-5e), 2.60–2.66 (m, 1H, cyclohexyl), 1.93 (m, 2H,
cyclohexyl), 1.73 (m, 2H, cyclohexyl), 1.66 (m, 1H, cyclohexyl),
1.34 (m, 4H, cyclohexyl), 1.19 (m, 1H, cyclohexyl). 13C NMR
(positive mode) m/z: calculated for
338.1175, found 338.1176.
C
15H20N3O4S [M+H]+
4.42. 5-Thio-b-D-xylopyranosyl-4-(2-naphthyl)-1,2,3-triazole
(10f)
(DMSO-d6 + e
D2O, 100 MHz): d = 152.0 (C-40), 120.3 (C-50), 77.8
(C-3), 75.5 (C-2), 72.7 (C-4), 62.1 (C-1), 34.7 (CH, cyclohexyl),
32.6 (CH2, cyclohexyl), 32.5 (CH2, cyclohexyl), 32.0 (C-5), 25.8
(CH2, cyclohexyl), 25.7 (2CH2, cyclohexyl). HR-LSIMS-MS (positive
mode) m/z: calculated for [M+H]+ C13H22N3O3S 300.1376, found
300.1375.
The title compound was prepared from 9f according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.29
(CH2Cl2/MeOH 9:1). Mp = 239–240 °C (MeOH). ½a D20
ꢃ
+34 (c 0.90/
e D2O, 400 MHz): d = 8.82 (s, 1H, H-
DMSO). 1H NMR (DMSO-d6 +
50), 8.42 (s, 1H, H-Ar), 7.91–8.03 (m, 4H, H-Ar), 7.49–7.56 (m, 2H,
H-Ar), 5.67 (d, 1H, J = 10.0 Hz, H-1), 3.95 (dd, 1H, J = 9.9, 8.9 Hz,
H-2), 3.60 (ddd, 1H, J = 10.7, 9.0, 4.4, H-4), 3.23 (pdd, 1H,
J = 8.8 Hz, H-3), 2.84 (dd, 1H, J = 13.4, 10.8, H-5a), 2.73 (dd, 1H,
4.46. 5-Thio-b-D-xylopyranosyl-4-(cyclohex-1-enyl)-1,2,3-
triazole (10j)
J = 13.4, 4.4 Hz, H-5e). 13C NMR (DMSO-d6 +
e
D2O, 100 MHz):
The title compound was prepared from 9j according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.31
d = 146.5 (C-40), 133.3 (C-Ar), 132.8 (C-Ar), 128.8 (CH-Ar), 128.2
(CH-Ar), 128.1 (C-Ar), 127.9 (CH-Ar), 126.8 (CH-Ar), 126.4 (CH-
Ar), 123.8 (CH-Ar), 123.7 (CH-Ar), 121.6 (C-50), 77.7 (C-3), 75.8
(C-2), 72.8 (C-4), 62.4 (C-1), 32.0 (C-5). HR-LSIMS-MS (positive
mode) m/z: calculated for C17H18N3O3S [M+H]+ 344.1063, found
344.1064.
(CH2Cl2/MeOH 9:1). Mp = 178–179 °C (MeOH). ½a D20
ꢃ
+28 (c 1.10/
e D2O, 400 MHz): d = 8.10 (s, 1H, H-
DMSO). 1H NMR (DMSO-d6 +
50), 6.40 (m, 1H, Csp2-H cyclohexenyl), 5.52 (d, 1H, J = 10.0 Hz, H-
1), 3.86 (dd, 1H, J = 9.9, 8.9 Hz, H-2), 3.55 (ddd, 1H, J = 10.6, 9.0,
4.5 Hz, H-4), 3.15 (pdd, 1H, J = 8.9 Hz, H-3), 2.76 (dd, 1H, J = 13.4,
10.7 Hz, H-5a), 2.67 (dd, 1H, J = 13.4, 4.6 Hz, H-5e), 2.28 (m, 2H,
cyclohexenyl), 212 (m, 2H, cyclohexenyl), 1.66 (m, 2H, cyclohexe-
4.43. 5-Thio-b-D-xylopyranosyl-4-(6-methoxy-2-naphthyl)-
1,2,3-triazole (10g)
nyl), 1.58 (m, 2H, cyclohexenyl). 13C NMR (DMSO-d6 +
e D2O,
100 MHz): d = 148.3 (C-40), 127.5 (C, cyclohexenyl), 124.4 (Csp2-
H, cyclohexenyl), 119.8 (C-50), 77.9 (C-3), 75.8 (C-2), 72.9 (C-4),
62.3 (C-1), 32.1 (C-5), 26.1 (CH2, cyclohexenyl), 25.0 (CH2, cyclo-
hexenyl), l22.4 (CH2, cyclohexenyl), 22.2 (CH2, cyclohexenyl). HR-
The title compound was prepared from 9g according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.30
(CH2Cl2/MeOH 9:1). Mp >250 °C (MeOH). ½a D20
ꢃ
+17 (c 1.21/DMSO).
1H NMR (DMSO-d6 +
e
D2O, 400 MHz): d = 8.59 (s, 1H, H-50), 8.22 (s,
LSIMS-MS (positive mode) m/z: calculated for C13H20N3O3S
1H, H-Ar), 7.81–7.85 (m, 3H, H-Ar), 7.26 (d, 1H, J = 2.1 Hz, H-Ar),
7.14 (dd, 1H, J = 9.0, 2.3 Hz, H-Ar), 5.59 (d, 1H, J = 10.0 Hz, H-1),
3.96 (pdd, 1H, J = 9.4 Hz, H-?), 3.81 (s, 3H, H- OCH3), 3.66 (pddd,
1H, J = 9.6, 4.9 Hz, H-4), 3.24 (pdd, 1H, 8.9 Hz), 2.69–2.85 (m, 2H,
[M+H]+ 298.1220, found 298.1213.
4.47. 1-(2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl)-4-
acetoxymethyl-1,2,3-triazole (S)-S-oxide (11a-S)
H-5a, H-5e). 13C NMR (DMSO-d6 +
e D2O, 100 MHz): d = 158.4 (C-
Ar), 147.5 (C-40), 134.8 (C-Ar), 130.4 (CH-Ar), 129.3 (C-Ar), 128.4
(CH-Ar), 125.9 (C-Ar), 124.8 (CH-Ar), 124.6 (CH-Ar), 121.9 (C-50),
119.8 (CH-Ar), 107.1 (CH-Ar), 78.2 (C-3), 76.3 (C-2), 73.1 (C-4),
63.1 (C-1), 56.1 (CH3-methoxy), 32.3 (C-5). HR-CI-MS (positive
mode) m/z: calculated for C18H20N3O4S [M+H]+ 374.1175, found
374.1174.
The title compound was prepared from 9a according to the gen-
eral procedure E, and isolated as a white powder (<5%). Rf = 0.19
(PE/EtOAc 4:6). Mp = 147–148 °C (CH2Cl2/PE).
½
a 2D0
+28 (c 1/
ꢃ
1
DMSO). H NMR (CDCl3, 400 MHz): d = 7.87 (s, 1H, H-50), 5.81
(dd, 1H, J = 11.4, 9.5 Hz, H-2), 5.54 (d, 1H, J = 11.4 Hz, H-1), 5.54
(pdd, 1H, J = 9.6 Hz, H-3), 5.20–5.33 (m, 1H, H-4), 5.22 (s, 2H,
CH2OAc), 3.89 (dd, 1H, J = 12.3, 3.7 Hz, H-5e), 3.25 (pdd, 1H,
J = 12.1 Hz, H-5a), 2.10, 2.07, 2.03, 1.81 (4s, 12H, acetyl). HR-
4.44. 5-Thio-b-D-xylopyranosyl-4-(4-methoxyphenyl)-1,2,3-
triazole (10h)
LSIMS-MS (positive mode) m/z: calculated for C16H22N3O9S
[M+H]+ 432.1077, found 432.1072.
The title compound was prepared from 9h according to the gen-
eral procedure D, and isolated as a white powder (99%). Rf = 0.31
4.48. 1-(2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl)-4-
acetoxymethyl-1,2,3-triazole (R)-S-oxide (11a-R)
(CH2Cl2/MeOH 9:1). Mp = 236–237 °C (MeOH). ½a D20
ꢃ
+37 (c 1.11/
DMSO). 1H NMR (DMSO-d6 +
e D2O, 400 MHz): d = 8.41 (s, 1H, H-
50), 7.71 (d, 2H, J = 8.2 Hz, 2H-Ar), 6.97 (d, 2H, J = 8.3 Hz, 2H-Ar),
5.55 (d, 1H, J = 10.0 Hz, H-1), 3.92 (pdd, 1H, J = 9.3 Hz, H-2), 3.72
(s, 3H, OCH3), 3.60–3.67 (m, 1H, H-4), 3.21 (pdd, 1H, J = 8.8 Hz,
The title compound was prepared from 9a according to the gen-
eral procedure E, and isolated as a white powder (<5%). Rf = 0.13
(PE/EtOAc 4:6). Mp = 142–143 °C (CH2Cl2/PE). ½a D20
ꢃ
+15 (c 0.49/

D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
39
1
DMSO). H NMR (CDCl3, 400 MHz): d = 7.99 (s, 1H, H-50), 6.15 (dd,
(1H, J = 11.3, 9.7 Hz, H-2), 5.81–5.87 (m, 1H, H-4), 5.82 (d, 1H,
J = 11.2 Hz, H-1), 5.54 (pdd, 1H, J = 9.8 Hz, H-3), 5.20 (s, 2H,
CH2OAc), 3.75 (dd, 1H, J = 14.3, 4.1 Hz, H-5e), 2.95 (dd, 1H,
J = 14.2, 12.0 Hz, H-5a), 2.08, 2.08, 2.06, 1.81 (4s, 12H, acetyl). 13C
NMR (CDCl3, 100 MHz): d = 170.7, 169.6, 169.3, 169.0 (4C, acetyl),
144.2 (C-40), 123.1 (C-50), 73.6 (C-1), 72.4 (C-3), 66.9 (C-2), 65.8
(C-4), 57.5 (CH2OAc), 46.7 (C-5), 20.9, 20.8, 20.6, 20.1 (4CH3, acet-
yl). HR-LSIMS-MS (positive mode) m/z: calculated for C16H22N3O9S
[M+H]+ 432.1077, found 432.1074.
4.53. 1-(3,4-Di-O-acetyl-b-
triazole S,S-dioxide (13)
D-xylal)-4-acetoxymethyl-1,2,3-
To a solution of 1-(2,3,4-tri-O-acetyl-5-thio-b-D-xylopyranosyl)-
4-acetoxymethyl-1,2,3-triazole 9a (1 equiv) in dry THF (5 mL/
0.3 mmol) was added dropwise a solution of m-CPBA (20 equiv)
in dry THF (5 mL/0.4 mmol). The mixture was stirred at rt for
60 min, diluted with EtOAc (50 mL), and washed successively with
saturated solutions of Na2S2O3 (50 mL), NaHCO3 (2 ꢂ 50 mL), and
NaCl (2 ꢂ 50 mL). The organic layer was dried (MgSO4), filtered,
and concentrated in vacuo. The crude product (white solid) was
purified by silica gel chromatography (Et2O/CH2Cl2 9:1) to afford
13 as a white powder (>99%). Rf = 0.29 (CH2Cl2/EtOAc 8:2). Mp
>250 °C (CH2Cl2/PE). 1H NMR (CDCl3, 400 MHz): d = 8.23 (s, 1H,
H-50), 6.91 (d, 1H, J = 4.1 Hz, H-2), 5.78 (dd, 1H, J = 6.4, 4.2 Hz, H-
3), 5.54 (ddd, 1H, J = 9.1, 6.4, 2.9 Hz, H-4), 5.25 (s, 2H, CH2OAc),
3.89 (dd, 1H, J = 14.1, 3.0 Hz, H-5e), 3.79 (dd, 1H, J = 14.0, 8.7 Hz,
H-5a), 2.16, 2.14, 2.09 (3s, 9H, acetyl). 13C NMR (CDCl3,
100 MHz): d = 170.8, 169.4, 169.4 (3C, acetyl), 144.0 (C-40), 137.4
(C-1), 124.2 (C-2), 124.1 (C-50), 66.9 (C-4), 66.8 (C-3), 57.2
(CH2OAc), 52.3 (C-5), 20.9, 20.8, 20.7 (3CH3, acetyl). HR-LSIMS-
4.49. 1-(2,3,4-Tri-O-acetyl-5-thio-b-
1,2,3-triazole (S)-S-oxide (11b-S)
D-xylopyranosyl)-4-phenyl-
The title compound was prepared from 9b according to the gen-
eral procedure E, and isolated as a white powder (<5%). Rf = 0.31
(CH2Cl2/EtOAc 8:2). Mp = 248–249 °C (CH2Cl2/PE). ½a D20
ꢃ
+14 (c 1/
1
DMSO). H NMR ((CD3)2CO, 400 MHz): d = 8.62 (s, 1H, H-50),
7.90–7.92 (m, 2H, H-Ar), 7.44–7.48 (m, 2H, H-Ar), 7.34–7.38 (m,
1H, H-Ar), 6.11 (d, 1H, J = 11.3 Hz, H-1), 5.95 (dd, 1H, J = 11.3,
9.6 Hz, H-2), 5.72 (pdd, 1H, J = 9.8 Hz, H-3), 5.47 (ddd, 1H,
J = 12.3, 10.0, 3.6 Hz, H-4), 3.97 (dd, 1H, J = 11.9, 3.6 Hz, H-5e),
3.63 (pdd, 1H, J = 12.1 Hz, H-5a), 2.06, 1.99, 1.78 (3s, 9H, acetyl).
HR-LSIMS-MS (positive mode) m/z: calculated for C19H21N3NaO7S
[M+Na]+ 458.0998, found 458.0101.
MS (positive mode) m/z: calculated for
388.0815, found 388.0818.
C
14H18N3O8S [M+H]+
4.54. 1-(2,3,4-Tri-O-acetyl-5-thio-b-D-xylopyranosyl)-4-
acetoxymethyl-1,2,3-triazole S,S-dioxide (14a)
4.50. 1-(2,3,4-Tri-O-acetyl-5-thio-b-
1,2,3-triazole (R)-S-oxide (11b-R)
D-xylopyranosyl)-4-phenyl-
The title compound was prepared from 9a according to the gen-
eral procedure F, and isolated as a white powder (>99%). Rf = 0.21
(CH2Cl2/EtOAc 9:1). Mp = 206–207 °C (CH2Cl2/PE);
½
a 2D0
+24
ꢃ
The title compound was prepared from 9b according to the gen-
eral procedure E, and isolated as a white powder (<5%). Rf = 0.28
1
(c 1/DMSO); H NMR (CDCl3, 400 MHz): d = 7.99 (s, 1H, H-50),
6.06 (d, 1H, J = 11.3 Hz, H-1), 5.82 (dd, 1H, J = 11.2, 9.6 Hz, H-2),
5.58 (pdd, 1H, J = 9.7 Hz, H-3), 5.39–5.46 (m, 1H, H-4), 5.22 (s,
2H, CH2OAc), 3.89 (dd, 1H, J = 14.4, 4.6 Hz, H-5e), 3.48 (dd, 1H,
J = 14.3, 11.6 Hz, H-5a), 2.10, 2.09, 2.07, 1.83 (4s, 12H, acetyl); 13C
NMR (CDCl3, 100 MHz): d = 170.8, 169.3, 161.2, 168.7 (4C, C=O),
144.2 (C-40), 123.8 (C-50), 75.1 (C-1), 71.9 (C-3), 68.3 (C-2), 66.2
(C-4), 57.4 (CH2OAc), 51.4 (C-5), 20.9, 20.7, 20.5, 20.0 (4CH3, acet-
yl); HR-LSIMS-MS (positive mode) m/z: calculated for
(CH2Cl2/EtOAc 8:2). Mp >250 °C (CH2Cl2/PE). ½a D20
ꢃ
+8 (c 0.50/
1
DMSO). H NMR ((CD3)2CO, 400 MHz): d = 8.40 (s, 1H, H-50),
7.93–7.96 (m, 2H, H-Ar), 7.45–7.48 (m, 2H, H-Ar), 7.35–7.39 (m,
1H, H-Ar), 6.41 (d, 1H, J = 11.4 Hz, H-1), 6.20 (dd, 1H, J = 11.3,
9.6 Hz, H-2), 5.85 (ddd, 1H, J = 11.9, 10.1, 4.0 Hz, H-4), 5.72 (pdd,
1H, J = 9.8 Hz, H-3), 3.86 (dd, 1H, J = 14.2, 4.0 Hz, H-5e), 3.49 (dd,
1H, J = 14.1, 12.1 Hz, H-5a), 2.06, 2.03, 1.78 (3s, 9H, acetyl). HR-
LSIMS-MS (positive mode) m/z: calculated for C19H21N3NaO7S
[M+Na]+ 458.0998, found 458.0100.
C
12H22N3O10S [M+H]+ 448.1026, found 448.1021.
4.55. 1-(2,3,4-Tri-O-acetyl-5-thio-b-
1,2,3-triazole S,S-dioxide (14b)
D-xylopyranosyl)-4-phenyl-
4.51. 1-(5-Thio-b-D-xylopyranosyl)-4-hydroxymethyl-1,2,3-
triazole (S)- and (R)-S-oxides (12a)
The title compound was prepared from 9b according to the gen-
eral procedure F, and isolated as a white powder (99%). Rf = 0.13
The title compound was prepared from a 80:20 mixture of 11a-
S and 11a-R according to the general procedure G, and isolated as a
white powder. Compounds 12a could not be obtained as pure dia-
stereoisomers and isomerization took place at the sulfur atom un-
der the acidic conditions used for their deacetylation leading to a
65:35 mixture of diastereosiomers. White powder (99%). Rf = 0.12
(CH2Cl2/MeOH 8:2); HR-LSIMS-MS (positive mode) m/z calculated
for C8H14N3O6S [M+H]+ 280.0603, found 280.0609.
(PE/EtOAc 7:3). Mp >250 °C (CH2Cl2/PE). ½a D20
ꢃ
+13 (c 1, DMSO). 1H
NMR (400 MHz, CDCl3) d = 8.86 (s, 1H, H-50), 7.93 (d, 2H,
J = 7.4 Hz, H-Ar), 7.48 (t, 2H, J = 7.6 Hz, H-Ar), 7.38 (t, 1H,
J = 7.4 Hz, H-Ar), 7.02 (d, 1H, J = 10.7 Hz, H-1), 5.87 (pdd, 1H,
J = 9.7 Hz, H-2), 5.78 (pdd, 1H, J = 9.7 Hz, H-3), 5.30 (m, 1H, H-4),
4.28 (dd, 1H, J = 13.9, 4.3 Hz, H-5e), 4.07 (dd, 1H, J = 13.7, 12.0 Hz,
H-5a), 2.06, 2.02, 1.80 (3S, 9H, acetyl). 13C NMR (100 MHz, CDCl3)
d = 169.2, 169.0, 168.4 (3C, acetyl), 147.0 (C-40), 129.6 (C-Ar),
129.0 (2CH-Ar), 128.6 (CH-Ar), 125.5 (2CH-Ar), 121.8 (C-50), 73.5
(C-1), 71.4 (C-3), 67.9 (C-2), 65.3 (C-4), 49.8 (C-5), 20.4, 20.1,
19.7 (3CH3, acetyl). HR-LSIMS-MS (positive mode) m/z: calculated
for C19H21N3NaO8S [M+Na]+ 474.0947, found 474.0944.
4.52. 1-(5-Thio-b-D-xylopyranosyl)-4-phenyl-1,2,3-triazole (S)-
and (R)-S-oxides (12b)
The title compound was prepared from pure 11b-S according to
the general procedure G, and isolated as a white powder. Com-
pounds 12b could not be obtained as pure diastereoisomers and
isomerization took place at the sulfur atom under the acidic condi-
tions used for their deacetylation leading to a 85:15 mixture of dia-
stereosiomers. White powder (99%). Rf = 0.14 (CH2Cl2/MeOH 9:1);
HR-LSIMS-MS (positive mode) m/z calculated for C13H16N3O5S
[M+H]+ 326.0811, found 326.0806.
4.56. 1-(-5-thio-b-D-xylopyranosyl)-4-hydroxymethyl-1,2,3-
triazole S,S-dioxide (15a)
The title compound was prepared from 14a according to the
general procedure G, and isolated as a white powder (99%).
Rf = 0.09 (CH2Cl2/MeOH 9:1). Mp = 242–243 °C (MeOH/CH2Cl2).

40
D. Goyard et al. / Carbohydrate Research 364 (2012) 28–40
a 2D0 +44 (c 1/DMSO). 1H NMR (DMSO-d6 +
e D2O, 400 MHz):
ꢃ
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Hayes, J. M.; Tiraidis, C.; Lazoura, E.; Leonidas, D. D.; Zographos, S. E.;
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Brunyánszki, A.; Docsa, T.; Gergely, P. Eur. J. Org. Chem. 2006, 2006, 4242–4256.
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½
d = 8.01 (s, 1H, H-50), 6.21 (d, 1H, J = 10.9 Hz, H-1), 4.54 (s, 2H,
CH2OH), 3.98 (dd, 1H, J = 10.8, 9.0 Hz, H-2), 3.69 (m, 1H, H-4),
3.60 (m, 2H, H-5a, H-5e), 3.54 (pdd, 1H, J = 9.0 Hz, H-3). 13C NMR
(100 MHz, DMSO-d6
+ e
D2O) d = 148.4 (C-40), 123.4 (C-50), 76.8
(C-3), 76.4 (C-1), 70.4 (C-2), 67.0 (C-4), 55.1 (CH2OH), 53.3 (C-5).
HR-CI-MS (positive mode) m/z: calculated for C8H14N3O6S [M+H]+
280.0598; found 280.0601.
4.57. 1-(5-Thio-b-D-xylopyranosyl)-4-phenyl-1,2,3-triazole S,S-
dioxide (15b)
22. Cecioni, S.; Argintaru, O.-A.; Docsa, T.; Gergely, P.; Praly, J.-P.; Vidal, S. New J.
Chem. 2009, 33, 148–156.
23. Chrysina, E. D.; Kosmopoulou, M. N.; Tiraidis, C.; Kardakaris, R.; Bischler, N.;
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The title compound was prepared from 14b according to the
24. Hadady, Z.; Somsák, L. Arkivoc 2004, vii, 140–149.
general procedure G, and isolated as a white powder (99%).
25. Tóth, M.; Kun, S.; Bokor, É.; Benltifa, M.; Tallec, G.; Vidal, S.; Docsa, T.; Gergely,
P.; Somsák, L.; Praly, J.-P. Bioorg. Med. Chem. 2009, 17, 4773–4785.
26. Bokor, É.; Docsa, T.; Gergely, P.; Somsák, L. Bioorg. Med. Chem. 2010, 18, 1171–
1180.
27. Chrysina, E. D.; Bokor, É.; Alexacou, K.-M.; Charavgi, M.-D.; Oikonomakos, G.
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Tetrahedron: Asymm. 2009, 20, 733–740.
Rf = 0.18 (CH2Cl2/MeOH 9:1). Mp >250 °C (MeOH/CH2Cl2). ½a D20
ꢃ
+17 (c 1/DMSO). 1H NMR (DMSO-d6 +
e D2O, 400 MHz): d = 8.74
(s, 1H, H-50), 7.92 (d, 2H, J = 7.4 Hz, H-Ar), 7.47 (pdd, 2H,
J = 7.6 Hz, H-Ar), 7.36 (pdd, 1H, J = 7.3 Hz, H-Ar), 6.33 (d, 1H,
J = 10.8 Hz, H-1), 4.08 (dd, 1H, J = 10.3, 9.3 Hz, H-2), 3.58–3.76
(m, 4H, H-3, H-4, H-5a, H-5e). 13C NMR (DMSO-d6 +
e D2O,
28. Docsa, T.; Czifrák, K.; Hüse, C.; Somsák, L.; Gergely, P. Mol. Med. Rep. 2011, 4,
477–481.
100 MHz): d = 146.6 (C-40), 130.3 (C-Ar), 129.2 (2CH-Ar), 128.4
(CH-Ar), 125.5 (2CH-Ar), 121.7 (C-50), 76.4 (C-3), 76.3 (C-1), 70.2
(C-2), 66.8 (C-4), 53.0 (C-5). HR-LSIMS-MS (positive mode) m/z:
calculated for C13H16N3O5S [M+H]+ 326.0805, found 326.0809.
}
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Financial supports from CNRS (PICS 2008–2010 n°4576), Uni-
versity Claude Bernard Lyon 1 and the French Agence Nationale
de la Recherche (support of the ANR project GPdia n°ANR-08-
BLAN-0305 for both salary and expenses of D.G.) are gratefully
acknowledged. Dr. F. Albrieux, C. Duchamp and N. Henriques are
gratefully acknowledged for mass spectrometry analyses. This
study was supported by a grant from the Hungarian Science
Research Fund (OTKA CNK80709) to P.G. and T.D. and FP7 Capaci-
ties coordination and support actions REGPOT-2008-1-No 230146
‘EUROSTRUCT’ and REGPOT-2009-1-No 245866 ‘ARCADE’ involv-
ing P.V.S., A.S.C. and E.D.C.T.D. thanks the Hungarian Academy of
Sciences for a János Bolyai Scholarship.
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