Synthesis of 1-(d-glucopyranosyl)-1,2,3-triazoles and their evaluation as glycogen phosphorylase inhibitors

Article abstract of DOI:10.1016/j.bmc.2009.12.043

1-(d-Glucopyranosyl)-1,2,3-triazoles were prepared from per-O-acetylated α- and β-d-glucopyranosyl azides as well as per-O-benzoylated (β-d-gluco-hept-2-ulopyranosylazide)onamide and onic acid methylester by using azide-alkyne cycloaddition catalysed by i

Full text of DOI:10.1016/j.bmc.2009.12.043

Bioorganic & Medicinal Chemistry 18 (2010) 1171–1180
Contents lists available at ScienceDirect
Bioorganic & Medicinal Chemistry
journal homepage: www.elsevier.com/locate/bmc
Synthesis of 1-(D-glucopyranosyl)-1,2,3-triazoles and their evaluation
as glycogen phosphorylase inhibitors
Éva Bokor a, Tibor Docsa b, Pál Gergely c, László Somsák a,
*
a Department of Organic Chemistry, Faculty of Science and Technology, University of Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary
b Cell Biology and Signaling Research Group of the Hungarian Academy of Sciences, Department of Medical Chemistry, Medical and Health Science Centre, University of
Debrecen, Egyetem tér 1, H-4032 Debrecen, Hungary
c Department of Medical Chemistry, Medical and Health Science Centre, University of Debrecen, Egyetem tér 1, 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:
1-(
D
-Glucopyranosyl)-1,2,3-triazoles were prepared from per-O-acetylated
a- and b-D-glucopyranosyl
Received 14 September 2009
Revised 9 December 2009
Accepted 15 December 2009
Available online 22 December 2009
azides as well as per-O-benzoylated (b-
ester by using azide-alkyne cycloaddition catalysed by in situ generated Cu(I) under aqueous conditions.
The O-acyl protecting groups were removed by the Zemplén protocol. The test compounds were assayed
against rabbit muscle glycogen phosphorylase b to show that the b-D-glucopyranosyl derivatives were
D-gluco-hept-2-ulopyranosylazide)onamide and onic acid methyl-
superior inhibitors as compared to the two other series of triazoles.
Keywords:
Ó 2009 Elsevier Ltd. All rights reserved.
1-(D-Glucopyranosyl)-1,2,3-triazole
Glycogen phosphorylase
Inhibitor
Azide–alkyne cycloaddition
1. Introduction
mixed character), and these contacts made the binding tighter.
Other representatives of glucopyranosylamines (Chart 1, B) had
an additional carboxamide group at the anomeric position (actu-
Glycogen phosphorylase (GP) is a validated target in the search
for new therapies of type 2 diabetes mellitus,1–5 therefore, the
quest for new inhibitors of GP attracts continuous interest in both
academia and industry. In the past two decades a very large array
of compounds were tested against various forms of GP, and these
were amply reviewed.1,2,6–9 The most populated class of inhibitors
of GP is that of the glucose analogues which are structurally char-
ally these are (N-acyl-b-D-gluco-hept-2-ulopyranosylamine)ona-
mides), and these compounds proved also micromolar
inhibitors.17–20
With the advent of the copper(I)-catalysed azide–alkyne cyclo-
addition reaction21–25 for the selective creation of 1,4-disubsti-
tuted 1,2,3-triazole derivatives, several examples show
similarity21 in respect of size, dipolar character, and H-bond accep-
tor capacity of the amide moiety and the 1,2,3-triazole ring.26–28
This resemblance underlines the more and more extensive use of
the 1,2,3-triazole moiety as a bioisosteric replacement29–31 for
the amide. The high chemical stability of the 1,2,3-triazole ring un-
der various chemical conditions32 is an additional supportive factor
to find new examples of this isosterism. Very recently, we have
acterised by a D-glucopyranose ring having either diverse substitu-
ents or spirocyclic moieties attached to the anomeric carbon.8–11
These compounds primarily bind to the active site of the enzyme
although some of them have also been detected by X-ray crystal-
lography at the so-called new allosteric site.12,13
N-Acyl-b-D
-glucopyranosylamines14–16 (Chart 1, A) were among
the first efficient glucose analogue inhibitors of GP. An increase in
the size of a properly oriented acyl group (R = 2-naphthyl) made
the inhibition stronger, and placing this group farther from the su-
gar with a rigid spacer (R = 2-(2-naphthyl)vinyl) resulted in the
best inhibitor of this series (for a detailed discussion of struc-
ture–activity relationship of these compounds see Refs. 9,16). As
it was shown by crystallographic studies9 the larger/longer R sub-
stituents had more extensive interactions in the b-channel of the
enzyme (an empty space in the direction of the b-anomeric substi-
demonstrated in a short communication33 that some N-acyl-b-
glucopyranosylamines and 1-(b- -glucopyranosyl)-4-substi-
D-
A
D
tuted-1,2,3-triazoles C having the same R appendages in the agly-
con exhibit reasonable coincidence of inhibition constants against
rabbit muscle glycogen phosphorylase b (RMGPb). Moreover, bind-
ing peculiarities as revealed by X-ray crystallographic studies on
the corresponding enzyme–inhibitor complexes indicated high
similarities in the binding mode for several of the studied pairs.
tuent of bound
D
-glucose surrounded by amino acid side chains of
An N-(b-D-glucopyranosyl)-4-phenyl-1,2,3-triazol-1-yl-acetam-
ide was also studied as inhibitor of GP.34 1-Glycosyl-1,2,3-triazol
type compounds were recently investigated as anticancer agents,35
inhibitors of galectins,36,37 carbonic anhydrase,38 and glycosidase
* Corresponding author. Tel.: +36 52 512 900; fax: +36 52 453 835.
E-mail addresses: somsak@tigris.unideb.hu, somsak@tigris.klte.hu (L. Somsák).
0968-0896/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.bmc.2009.12.043

1172
Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
enzymes,39 as well as to their binding affinities to lectins,40 and
cytostatic activity.41
HO
HO
HO
HO
HO
HO
O
H
N
O
H
N
R
R
OH
HO
H2N
In this paper we disclose our investigations on the synthesis of
O
O
O
1-(D-glucopyranosyl)-4-substituted-1,2,3-triazoles of a- (D) and b-
D-gluco (C, E, F) configurations. These compounds were tested as
inhibitors of RMGPb, and the inhibitions compared to those of
the corresponding amide derivatives and other related compounds.
A
B
Ki*
[µM]
3214
8114
14415
1016
1333
Ki*
[µM]
R
R
2. Results and discussion
2.1. Syntheses
Me
Me
31017,18
OMe
1619,20
O-Peracetylated b-
with terminal alkynes a–f (Table 1) in water44 in the presence of
CuSO4 and -ascorbic acid at 70 °C. The cycloadditions proceeded
cleanly to complete conversion of the starting material in ꢀ8 h to
give the corresponding 1-(b- -glucopyranosyl)-1,2,3-triazoles 2 in
D
-glucopyranosyl azide42,43 (1) was reacted
L
3.516
D
very good yields. Removal of the protecting groups was effected
by the Zemplén protocol and compounds 3 were obtained in high
yields. Ester 2b was also treated by NaOH as well as NH3 in MeOH
to get carboxylate 3biii and carboxamide 3biv, respectively. Other
preparations of 2a,32 2b,44 2c,44,45,39 3a,32 and 3c39 were published.
*Inhibitor constants determined with rabbit muscle GPb
HO
O
HO
N
HO
R
HO
HO
HC
N
O
HO
N
N
N
HO
The protected
similar manner from O-peracetylated
a
-
D
-glucopyranosyl triazoles 5 were obtained in a
N
OH
a
-D
-glucopyranosyl azide46,43
R
(4). Azide 4 showed no transformation with a in the presence of
1.5 mol % Cu catalyst during 8 h. Therefore, higher catalyst load
(7.5 mol %) was applied. However, the yields of these reactions in
approximately the same reaction times were lower than those for
C
D
R
R
HO
HO
HO
HO
O
O
HO
N
O
N
N
N
HO
the b-
the azido group may account for this. This is in accord with the lit-
erature experience that the preparation of an O-perbenzylated
D-derivatives, and probably the higher steric hindrance of
N
N
HO
H2N
HO
MeO
O
a-D-
E
F
glucopyranosyl-triazole required an excess of alkyne, 40 mol % cat-
alyst, 48 h reaction time, and elevated temperature.32 Deprotection
by the Zemplén method gave compounds 6, and carboxylate 6biii
as well as carboxamide 6biv were obtained as described above.
Chart 1.
Table 1
Synthesis of 1-(b-D-glucopyranosyl)-4-substituted-1,2,3-triazoles
R
R
R
C
CH
AcO
AcO
AcO
AcO
AcO
AcO
HO
HO
HO
ii or iii or iv
a-f
O
O
O
N3
N
N
N
N
i
N
N
OAc
OAc
OH
3
1
2
i) 1.5 mol% CuSO4, 20 mol% L-ascorbic acid, H2O, 70 °C, 8h;
ii) NaOMe/dry MeOH, r. t.; iii) NaOH/MeOH, r. t.; iv) NH3/dry MeOH, r. t.
Alkyne
R
Conditions and yields (%)
2
3
a
b
ꢁCH2OH
ꢁCO2Et
i
i
65a
89c
ii
ii
iii
iv
82b
70
55
86
3bii
3biii
3biv
R = CO2Me
R = CO2Na
R = CONH2
c
i
i
58d
71
ii
ii
89e
d
72
e
f
i
i
67
96
ii
ii
95
95
a
Reported yield by a different method: 92%.32
Literature preparation of 3a by deprotection of per-O-acetylated or benzoylated or benzylated 1-b-D-glucopyranosyl-4-acetoxy- or benzoyloxy- or benzyloxymethyl-
b
1,2,3-triazoles.32
Reported yield: 92%.44
c
d
Reported yields by different methods: 85%,44 91%,45 75%.39
Reported yield: 72%.39
e

Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
1173
Table 2
Synthesis of 1-(a-D-glucopyranosyl)-4-substituted-1,2,3-triazoles
R
C CH
AcO
AcO
AcO
AcO
AcO
AcO
HO
HO
HO
a-c
O
O
ii or iii or iv
O
HO
N
i
AcO
AcO
N3
N
N
N
N
N
4
5
6
R
R
i) 7.5 mol% CuSO4, 20 mol% L-ascorbic acid, H2O, 70 ºC, 8h; ii) NaOMe/dry MeOH, r. t.;
iii) NaOH/MeOH, r. t; iv) NH3/dry MeOH, r. t.
Alkyne
R
Conditions and yields (%)
5
6
a
ꢁCH2OH
ꢁCO2Et
i
i
36
ii
72
iii
iv
ii
6bii
6biii
6biv
93
47
81
R = CO2Me
R = CO2Na
R = CONH2
b
72
39
c
i
ii
75
In both series ethyl propiolate (b) gave markedly higher yields
than the other alkynes that is in accord with previous experiences
showing higher reactivity for electron depleted alkynes.22,25
Reactions of O-perbenzoylated (b-D-gluco-hept-2-ulopyranosy-
lazide)onic acid derivatives 7 and 8 were different in several as-
may be accounted for by the sterically more crowded environment
of the azido group in 7 and 8 than in 1. Additionally, the existence
of a H-bond between the CONH2 and the azide in amide 7 demon-
strated by CD spectroscopy47 may also disfavour the reaction. An-
other factor can be the higher solubility of acetylated sugar
derivatives in water as compared to that of benzoylated com-
pounds.48 The possible role of the solubility can be rationalised
by the reactions in aqueous CH3NO2 (conditions ii) and in DMSO
(conditions iii) with a slightly higher catalyst ratio where both
the conversions and the yields raised. Compounds 9 and 10 were
deprotected under usual circumstances to give 11 and 12,
respectively.
pects (Table 3). The aqueous conditions which worked well in
the
a- and b-D-glucosyl azide (1 and 4, respectively) series, facili-
tated transformations only with the most reactive ethyl propiolate
(b) while the other alkynes did not react in one day (conditions i).
However, the conversion of the starting materials 7 and 8 to give
9b and 10b, respectively, was not complete in 8 h, a reaction time
sufficient for total consumption of 1 and 4 (Tables 1 and 2). This
Table 3
Synthesis of [1-(b-D-gluco-hept-2-ulopyranosyl)-4-substituted-1,2,3-triazole]onic acid derivatives
R
R
R
C CH
BzO
BzO
BzO
BzO
BzO
BzO
HO
HO
HO
iv or v
O
O
a-d
O
N
N
N
N
N3
i or ii or iii
N
N
BzO
BzO
HO
R'
R'
R'
7 R' = CONH2
8 R' = CO2Me
9 R' = CONH2
10 R' = CO2Me
11 R' = CONH2
12 R' = CO2Na
i) 7.5 mol% CuSO4, 20 mol% L-ascorbic acid, H2O, 70 ºC; ii) 11 mol% CuSO4, 30 mol% L-ascorbic
acid, H2O:CH3NO2 2:1, 70 ºC; iii) 11 mol% CuSO4, 30 mol% L-ascorbic acid, DMSO, 70 ºC; iv)
NaOMe/dry MeOH, r. t.; v) NaOH/MeOH, r. t.
Alkyne
R
Conditions and yields (%)
R. time
Conversion
Yield
a
ꢁCH2OH
i
ii
iii
9a
1 d
2 d
1 d
No reaction
43
51
67
75
iv
11a
68
b
c
ꢁCO2Et
i
i
9b
10b
8 h
8 h
63
74
56
70
v
v
11b
12b
R = CO2Na
R = CO2Na
67
35
i
9c
1 d
No reaction
iv
iv
11c
11d
92
81
ii
iii
2 d
1 d
44
73
98
83
d
i
9d
1 d
No reaction
ii
iii
2 d
1 d
37
63
86
87

1174
Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
Table 4
Inhibition (Ki or *IC50
[
lM]) of rabbit muscle glycogen phosphorylase b by the new compounds and the corresponding N-acyl-b-D-glucopyranosylamines (13)
R
HO
HO
HO
R
H
N
O
O
R
HO
HO
HO
HO
HO
HO
O
O
HO
N
N
HO
N
N
N
O
N
N
N
HO
HO
R
CONH2
N
R
3
6
11
13
ꢁCH2OH
a
26
670*
No inh. at 625
l
M
20
1433
500*
1833
21055
—
ꢁCO2Me
ꢁCO2Na
ꢁCONH2
3bii
3biii
3biv
6bii
6biii
6biv
30% at 625
400*
No inh. at 625
l
M
—
20% at 625
350*
lM
11b
No inh. at 625
—
l
M
M
l
M
M
—
162
8114
c
No inh. at 625
l
No inh. at 625
780*
l
15133
14415
36
1016
d
—
—
—
1633
1333
625*
e
f
—
—
44416
13633
600*
1100*16
3214
ꢁCH3
14
CO2Na
HO
HO
HO
HO
HO
O
O
O
HO
HO
NHCOOCH3
CONH2
NHCOCH3
CONH2
H
HO
HO
HO
O
HO
HO
HO
HO
N
N
HO
CONH2
N
HO
CO2Na
12b No inh. at 625
l
M
15 1619,20
16 31017,18
17 37051
2.2. Inhibition studies
The new 1-( -glucopyranosyl)-1,2,3-triazole derivatives were
Compounds of the series 3 and 13 with the same R group show
very similar inhibition in most cases. In both series the hydroxy-
methyl (a) and 2-naphthyl (d) derivatives are the most efficient
ones, and the similarity is remarkable also for the other pairs. X-
ray crystallography revealed a very high degree of similitude in
the binding modes of 3a and 13a as well as of 3d and 13d at the
catalytic site of RMGPb.33 Although for other investigated pairs
(3c and 13c; 3e and 13e) the structural similarity of the en-
zyme–inhibitor complexes was not so profound, it was suggested
that these observations form the basis of a bioisosteric relationship
of amide and 1,2,3-triazoles for the glycogen phosphorylase case.
Other possibilities for non-classical heterocyclic bioisosteres of
amide have been reported.52
D
evaluated as inhibitors of rabbit muscle glycogen phosphorylase
b (RMGPb) as described earlier,15,49 and the results are collected
in Table 4. For comparison, inhibitory efficiencies of N-acyl-b-
glucopyranosylamines (13) with the same R group are also shown.
Among the three series of triazoles 3, 6 and 11 the b- -glucopyran-
osyl derivatives 3 exhibit the strongest inhibition with some com-
pounds (3a, 3d) in the low micromolar range. The
D-
D
a-D-
glucopyranosyl derivatives 6 are generally significantly less effi-
cient, except carboxylate 6biii showing slightly stronger inhibition
than the corresponding b-D-configured 3biii. Compounds 11 are
non-inhibitory with the exception of the 2-naphthyl derivative
11d which is a very weak inhibitor.
It is also noticeable that the 2-naphthyl derivatives 3d, 11d and
13d are the strongest inhibitors in each corresponding class of
compounds. This observation corroborates several other find-
ings52–54 and indicate the importance of extensive interactions of
the inhibitors in the b-channel of the enzyme.
The higher activities of the b-anomers compared to those of the
a-derivatives are in accord with literature results showing stronger
inhibition for several b-anomeric derivatives over their -counter-
a
parts (e.g., CH2N3, CH2OSO2CH3, CONHCH3, CONHNH2, CONHCH2-
15
CH2OH,50,51 NHCOCF3 as substituents of the anomeric carbon).
3. Conclusion
The observable but weak inhibition by 6a and 6biii may reveal
favourable polar/ionic contacts with the enzyme, however, does not
Copper(I)-catalysed azide–alkyne cycloaddition reaction was
break the general tendency that
a-anomeric substituents of the D-
used to prepare O-acetyl or O-benzoyl protected 1-
D-glycopyrano-
glucopyranosyl ring are not really efficient to make a good inhibitor.
syl-1,2,3-triazoles of the - and b- -glucopyranosyl as well as (b-D-
a
D
A comparison of series 3 to 11 clearly shows that the introduc-
gluco-hept-2-ulopyranosyl)onic acid derivatives series. Removal of
the protecting groups according to the Zemplén protocol gave test
compounds which were assayed as inhibitors of rabbit muscle gly-
cogen phosphorylase b. The 1-(b-D-glucopyranosyl)-1,2,3-triazoles
proved the best inhibitors among the three series of compounds
exhibiting inhibition constants in the low micromolar range. The
tion of a CONH2 group in the
the inhibition. Among compounds with an
a
-position is highly detrimental for
-CONH2 substituent
a
only methyl carbamate 15 (b-NHCOOCH3) was reported to show
considerable inhibition,19,20 while in case of other b-substituents
(b-NHCOCH3 (16), or b-N3 Ki = 1800
icantly weaker.17,18 Introduction of an
inhibitor also from N-acetyl-b- -glucopyranosylamine (compare
l
M) the activity proved signif-
a-CONH2 makes a weaker
a-
D
-configured derivatives were almost inefficient, and the intro-
duction of an -CONH2 group at the anomeric position of the
b- -configured series also resulted in a practical loss of activity.
1-(b- -Glucopyranosyl)-1,2,3-triazoles and N-acyl-b- -glucopyr-
anosylamines are remarkably similar in their inhibition properties.
D
a
14 and 16). Compounds 11 can also be considered as derivatives
of anhydro-heptonamide 17 to show that the inhibition becomes
weaker even in this comparison.
D
D
D

Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
1175
As X-ray crystallography demonstrated similarity of the binding
mode at the catalytic site, these observations confirm the bioisos-
teric relationship of amides and 1,2,3-triazoles for the glycogen
phosphorylase case, as well.
monitored by TLC (1:1 EtOAc–hexane). When the TLC showed no
more change (conversions were incomplete), the mixture was
cooled to rt, water (15 mL) was added, and extracted with diethyl
ether (5 ꢃ 30 mL). The combined organic phase was dried, concen-
trated under diminished pressure, and the crude product was puri-
fied by column chromatography.
4. Experimental
4.5. General procedure IV for the Zemplén-deacylation
(3a,bii,c,d–f, 6a,bii,c, 11a,c,d)
4.1. General methods
Melting points were measured in open capillary tubes or on a
Kofler hot-stage and are uncorrected. Optical rotations were deter-
mined with a Perkin–Elmer 241 polarimeter at rt. NMR spectra were
recorded with Bruker 200 (200/50 MHz for 1H/13C), Bruker 360
(360/90 MHz for 1H/13C) or Avance DRX 500 (500/125 MHz for
1H/13C) spectrometers. Chemical shifts are referenced to Me4Si
(1H), or to the residual solvent signals (13C). TLC was performed on
DC-Alurolle Kieselgel 60 F254 (Merck), and the plates were visualised
under UV light and by gentle heating. For column chromatography
Kieselgel 60 (Merck, particle size 0.063–0.200 mm) was used.
Dichloromethane was distilled from P4O10 and acetone from CaSO4)
and stored over 4 Å molecular sieves. Organic solutions were dried
over anhydrous MgSO4 and concentrated under diminished pres-
sure at 40–50 °C (water bath). Propargyl alcohol (a), ethyl propiolate
(b), phenylacetylene (c), and 3-phenyl-1-propyne (f) and pentam-
ethylcyclopentadienyl-bis(triphenylphosphine)ruthenium(II) chlo-
ride were purchased from Aldrich. 1-56 and 2-Naphthylacetylene57
were synthesised according to published procedures.
An acetylated or benzoylated compound was dissolved in dry
MeOH (5 mL/100 mg, a few drops of CHCl3 were added in case of
incomplete dissolution) and a catalytic amount of a NaOMe solu-
tion (ꢀ1 M in MeOH) was added. The mixture was kept at rt and
monitored by TLC (7:3 CHCl3–MeOH). When the starting material
was consumed the mixture was neutralised with a cation exchange
resin Amberlyst 15 (H+ form), then the resin was filtered off and
the solvent removed. If the residue was chromatographically not
uniform, it was purified by column chromatography.
4.6. General procedure V for the deacylation of the glucose
derivatives containing ester groups (3biii, 6biii, 11b, 12b)
An acetylated or benzoylated compound was dissolved in dry
MeOH (5 mL/100 mg) and 1 M methanolic NaOH (2–4 equiv) was
added. The reaction mixture was kept at rt and monitored by TLC
(7:3 CHCl3–MeOH). After completion of the reaction, the deposited
crystalline product was filtered off and purified by column
chromatography.
4.2. General procedure I for the preparation of 1-(20,30,40,60-
tetra-O-acetyl-b-
triazoles (2a–f) (adapted from Ref. 44)
D-glucopyranosyl)-4-substituted-1,2,3-
4.7. 1-(20,30,40,60-Tetra-O-acetyl-b-
hydroxymethyl-1,2,3-triazole (2a)
D-glucopyranosyl)-4-
2,3,4,6-Tetra-O-acetyl-b-
the corresponding alkyne (2.7 mmol), CuSO4ꢂ5H2O (10 mg,
0.04 mmol) and -ascorbic acid (100 mg, 0.57 mmol) were heated
in water (15 mL) at 70 °C with vigorous stirring and monitored
by TLC (1:1 EtOAc–hexane). After completion of the reaction, the
heterogeneous mixture was cooled to rt and then in an ice bath,
the solid was filtered off and washed with water. The crude prod-
uct was purified by crystallisation or column chromatography.
D-glucopyranosyl azide (1, 1 g, 2.7 mmol),
From
1 (1 g, 2.68 mmol) and propargyl alcohol (0.16 mL,
2.70 mmol) according to General procedure I. Purified by recrystal-
L
lisation from ethanol to yield 0.75 g (65%) white solid. Mp: 152–
154 °C (lit.32 mp: 150–151 °C); [
a]
D = ꢁ29 (c 0.22, CHCl3); 1H and
13C NMR data correspond to the reported spectra.32
4.8. Ethyl 1-(20,30,40,60-tetra-O-acetyl-b-
D-glucopyranosyl)-1,2,3-
triazole-4-carboxylate (2b)
4.3. General procedure II for the preparation of 1-(20,30,40,60-
From
1 (1 g, 2.68 mmol) and ethyl propiolate (0.28 mL,
tetra-O-acetyl-
triazoles (5a–c), [1-(30,40,50,70-tetra-O-benzoyl-b-
ulopyranosyl)-4-ethoxycarbonyl-1,2,3-triazole]onamide (9b)
and methyl [1-(30,40,50,70-tetra-O-benzoyl-b-
-gluco-hept-2-
a-
D
-glucopyranosyl)-4-substituted-1,2,3-
2.70 mmol) according to General procedure I. Purified by recrystal-
lisation from ethanol to yield 1.12 g (89%) white solid. Mp: 172–
D
-gluco-hept-2-
174 °C; [a]
D = ꢁ62 (c 0.21, CHCl3); 1H NMR (CDCl3): d (ppm) 8.40
(1H, s, triazole H), 5.98 (1H, d, J1 ,2 9.2 Hz, H-10), 5.49–5.41 (2H,
D
0
0
m, H-20, H-30), 5.27 (1H, pseudot, J3 ,4 9.2 Hz, J4 ,5 9.2 Hz, H-40),
ulopyranosyl)-4-ethoxycarbonyl-1,2,3-triazole]onate (10b)
0
0
0
0
4.44 (2H, q, J 7.3 Hz, CH2), 4.32 (1H, dd, J6 a,6 b 13.2 Hz, H-60a),
0
0
4.17 (1H, dd, J5 ,6 b 2.6 Hz, H-60b), 4.08 (1H, ddd, J5 ,6 a 5.3 Hz, H-
50), 2.10, 2.08, 2.04, 1.90 (12H, 4s, 4 ꢃ CH3), 1.42 (3H, t, J 7.3 Hz,
CH3); 13C NMR (CDCl3): d (ppm) 170.3, 169.7 169.2, 168.8 (CO),
160.1 (COOEt), 140.8 (triazole C-4), 126.0 (triazole C-5), 85.7 (C-
10), 75.2, 72.2, 70.3, 67.4 (C-20–C-50), 61.5, 61.3 (C-60, CH2), 20.5,
20.4 (2), 19.9 (CH3), 14.1 (CH3). Anal. Calcd for C19H25N3O11
(471.42): C, 48.41; H, 5.35; N, 8.91; Found: C, 48.34; H, 5.40; N,
8.99.
An azide (4 or 7 or 8, 2.7 mmol), the corresponding alkyne
0
0
0
0
(2.7 mmol), CuSO4ꢂ5H2O (50 mg, 0.2 mmol) and
L-ascorbic acid
(100 mg, 0.57 mmol) were heated in water (1.5 mL/100 mg azide)
at 70 °C with vigorous stirring and monitored by TLC (1:1 EtOAc–
hexane). After completion of the reaction, the heterogeneous mix-
ture was cooled to rt and then in an ice bath, the solid was filtered
off and washed with water. The crude product was purified by col-
umn chromatography.
4.4. General procedure III for the preparation of [1-(30,40,50,70-
4.9. 1-(20,30,40,60-Tetra-O-acetyl-b-
D-glucopyranosyl)-4-phenyl-
tetra-O-benzoyl-b-D-gluco-hept-2-ulopyranosyl)-4-substituted-
1,2,3-triazole (2c)
1,2,3-triazole]onamides (9a,c,d)
From
1 (1 g, 2.68 mmol) and phenylacetylene (0.30 mL,
[(3,4,5,7-Tetra-O-benzoyl-b-
onamide (7, 100 mg, 0.15 mmol), the corresponding alkyne
(0.3 mmol), CuSO4ꢂ5H2O (4 mg, 0.017 mmol) and -ascorbic acid
(8 mg, 0.045 mmol) were heated in DMSO (3 mL) at 70 °C and
D-gluco-hept-2-ulopyranosyl)azide]
2.70 mmol) according to General procedure I. Purified by recrystal-
lisation from ethanol to yield 0.74 g (58%) white solid. Mp: 214–
216 °C (lit.44 mp 198–202 °C, lit.39 mp 213–215 °C, lit.58 mp
L
218 °C); [
a]
D = ꢁ123 (c 0.2, CHCl3) (lit.44
[a
]D = ꢁ86 (c 1.0, CH2Cl2),

1176
Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
lit.58
[a
]
D = ꢁ65 (c 0.95 CHCl3)); 1H and 13C NMR data correspond
163 °C); [
a
]
D = ꢁ5 (c 0.16, H2O); 1H NMR (D2O): d (ppm) 8.18
to the reported spectra.44,39
(1H, s, triazole H), 5.73 (1H, d, J1 ,2 9.2 Hz, H-10), 4.74 (2H, s,
0
0
CH2), 4.00 (1H, pseudot, J2 ,3 9.2 Hz, H-20), 3.90 (1H, dd, J6 a,6 b
0
0
0
0
4.10. 1-(20,30,40,60-Tetra-O-acetyl-b-
naphthyl)-1,2,3-triazole (2d)
D
-glucopyranosyl)-4-(2-
11.9 Hz, J5 ,6 a <1 Hz, H-60a), 3.80–3.59 (4H, m, H-30, H-40, H-50, H-
60b); 13C NMR (D2O): d (ppm) 147.7 (triazole C-4), 123.9 (triazole
C-5), 88.0 (C-10), 79.5, 76.6, 72.9, 69.6 (C-20–C-50), 61.0 (C-60),
55.2 (CH2). Anal. Calcd for C9H15N3O6 (261.24): C, 41.38; H, 5.79;
N, 16.09. Found: C, 41.25; H, 5.86; N, 16.17.
0
0
From 1 (0.35 g, 0.94 mmol) and 2-naphthylacetylene (0.14 g,
0.94 mmol) according to General procedure I. Purified by column
chromatography (1:2 EtOAc–hexane) to yield 0.35 g (71%) white
solid. Mp: 262–263 °C; [
(DMSO-d6): d (ppm) 9.12 (1H, s, triazole H), 8.44 (1H, s, aromatic),
a]
D = ꢁ194 (c 0.25, DMSO); 1H NMR
4.14. Methyl 1-(b-
carboxylate (3bii)
D-glucopyranosyl)-1,2,3-triazole-4-
8.05–7.95 (4H, m, aromatics), 7.59–7.55 (2H, m, aromatics), 6.47
(1H, d, J1 ,2 9.2 Hz, H-10), 5.73, 5.65, 5.22 (3 ꢃ 1H, 3pseudot, J
From 2b (0.26 g, 0.55 mmol) according to General procedure IV.
Purified by column chromatography (8:2 CHCl3–MeOH) to yield
0.11 g (70%) colourless syrup. Rf: 0.44 (7:3 CHCl3–MeOH);
0
0
9.2 Hz in each, H-20, H-30, H-40), 4.46 (1H, ddd, J4 ,5 9.2 Hz, J5 ,6 a
0
0
0
0
5.3 Hz, H-50), 4.20 (1H, dd, J6 a,6 b 13.2 Hz, H-60a), 4.13 (1H, dd,
0
0
J5 ,6 b 2.6 Hz, H-60b), 2.07, 2.03, 2.00, 1.84 (12H, 4s, 4 ꢃ CH3); 13C
NMR (DMSO-d6): d (ppm) 170.0, 169.5 169.4, 168.6 (CO), 146.9
(triazole C-4), 133.0, 132.7, 128.6, 128.0, 127.7, 127.4, 126.7,
126.3, 123.7, 123.5, 120.7 (aromatics, triazole C-5), 83.9 (C-10),
73.2, 72.0, 70.3, 67.5 (C-20–C-50), 61.8 (C-60), 20.5, 20.4, 20.2, 19.9
(CH3). Anal. Calcd for C26H27N3O9 (525.52): C, 59.42; H, 5.18; N,
8.00. Found: C, 59.51; H, 5.10; N, 8.12.
[a]
D = +4 (c 0.22, H2O); 1H NMR (D2O): d (ppm) 8.77 (1H, s, triazole
0
0
H), 5.81 (1H, d, J1 ,2 9.2 Hz, H-10), 4.00 (1H, pseudot, J2 ,3 9.2 Hz, H-
0
0
0
0
20), 3.90 (3H, s, OMe), 3.80 (1H, dd, J6 a,6 b 11.9 Hz, J5 ,6 a <1 Hz, H-
0
0
0
0
60a), 3.76–3.69 (3H, m, H-30, H-50, H-60b), 3.62 (1H, pseudot, J3 ,4
0
0
9.2, Hz, J4 ,5 9.2 Hz, H-40). 13C NMR (D2O): d (ppm) 162.2 (CO),
139.5 (triazole C-4), 128.9 (triazole C-5), 87.9 (C-10), 79.2, 76.0,
72.5, 69.0 (C-20–C-50), 60.6 (C-60), 52.9 (OMe). Anal. Calcd for
C10H15N3O7 (289.25): C, 41.53; H, 5.23; N, 14.53. Found: C, 41.43;
H, 5.33; N, 14.45.
0
0
4.11. 1-(20,30,40,60-Tetra-O-acetyl-b-
D-glucopyranosyl)-4-(1-
naphthyl)-1,2,3-triazole (2e)
4.15. Sodium 1-(b-D-glucopyranosyl)-1,2,3-triazole-4-
From 1 (0.35 g, 0.94 mmol) and 1-naphthylacetylene (0.14 g,
0.94 mmol) according to General procedure I. Purified by column
chromatography (1:2 EtOAc–hexane) to yield 0.33 g (67%) white
carboxylate (3biii)
From 2b (0.25 g, 0.53 mmol) according to General procedure V.
Yield 0.09 g (55%) white solid. Mp: 198–201 °C; [ D = ꢁ12 (c 0.18,
H2O); 1H NMR (D2O): d (ppm) 8.37 (1H, s, triazole H), 5.67 (1H, d,
solid. Mp: 217–219 °C; [
a
]
D = ꢁ103 (c 0.22, DMSO); 1H NMR
a]
(DMSO-d6): d (ppm) 8.99 (1H, s, triazole H), 8.34 (1H, s, aromatic),
J1 ,2 9.2 Hz, H-10), 3.93 (1H, pseudot, J2 ,3 9.2 Hz, H-20), 3.84 (1H, dd,
0
0
0
0
8.00 (2H, m, aromatics), 7.76 (1H, m, aromatic), 7.60–7.58 (3H, m,
aromatics), 6.48 (1H, d, J1 ,2 9.2 Hz, H-10), 5.85, 5.65, 5.24 (3 ꢃ 1H,
J6 a,6 b 11.9 Hz, J5 ,6 a <1 Hz, H-60a), 3.76–3.52 (4H, m, H-30, H-40, H-
50, H-60b); 13C NMR (D2O): d (ppm) 167.8 (CO), 145.8 (triazole C-
4), 127.0 (triazole C-5), 88.3 (C-10), 79.6, 76.6, 72.9, 69.6 (C-20–C-
50), 61.1 (C-60).
0
0
0
0
0
0
3pseudot, J 9.2 Hz in each, H-20, H-30, H-40), 4.45 (1H, ddd, J4 ,5
0
0
9.2 Hz, J5 ,6 a 5.3 Hz, J5 ,6 b 2.6 Hz, H-50), 4.20–4.15 (2H, m, H-60a,
H-60b), 2.05, 2.01, 1.99, 1.86 (12H, 4s, 4 ꢃ CH3); 13C NMR (DMSO-
d6): d (ppm) 170.0, 169.5 169.4, 168.7 (CO), 145.9 (triazole C-4),
133.5, 130.1, 128.9, 128.5, 127.3, 127.0, 126.8, 126.1, 125.5,
125.0, 123.1 (aromatics, triazole C-5), 84.0 (C-10), 73.2, 71.9, 70.4,
67.5 (C-20–C-50), 61.7 (C-60), 20.5, 20.4, 20.2, 19.9 (CH3). Anal. Calcd
for C26H27N3O9 (525.52): C, 59.42; H, 5.18; N, 8.00. Found: C, 59.30;
H, 5.09; N, 8.15.
0
0
0
0
4.16. 1-(b-D-Glucopyranosyl)-1,2,3-triazole-4-carboxamide (3biv)
Compound 2b (0.8 g, 1.7 mmol) was stirred in dry methanolic
NH3 (6 mL) at rt for 1 day. After completion of the reaction (mon-
itored by TLC 7:3 CHCl3–MeOH), the solvent was removed to give
white crystalline product. Yield: 0.40 g (86%). Mp: 227–229 °C
4.12. 1-(20,30,40,60-Tetra-O-acetyl-b-
D
-glucopyranosyl)-4-benzyl-
(lit.59 mp 232 °C); [
a]
D = ꢁ3 (c 0.19, DMSO) (lit.59
[a]D = +2 (c 0.5,
1,2,3-triazole (2f)
H2O)); 1H NMR (D2O): d (ppm) 8.64 (1H, s, triazole H), 5.79 (1H,
d, J1 ,2 9.2 Hz, H-10), 3.99 (1H, pseudot, J2 ,3 9.2 Hz, H-20), 3.87
0
0
0
0
(1H, dd, J6 a,6 b 11.9 Hz, J5 ,6 a 5.3 Hz, H-60a), 3.78–3.67 (3H, m, H-
0
0
0
0
From 1 (1 g, 2.68 mmol) and 3-phenyl-1-propyne (0.34 mL,
2.70 mmol) according to General procedure I. Purified by recrystal-
lisation from ethanol to yield 1.26 g (96%) white solid. Mp: 175–
30, H-50, H-60b), 3.60 (1H, pseudot, J3 ,4 9.2 Hz, J4 ,5 9.2 Hz, H-40).
(DMSO-d6): d (ppm) 7.05 (1H, s, CONH2), 6.66 (1H, s, CONH2). 13C
NMR (D2O): d (ppm) 164.1 (CO), 142.1 (triazole C-4), 126.9 (tria-
zole C-5), 87.8 (C-10), 79.2, 76.0, 72.5, 69.1 (C-20–C-50), 60.6 (C-
60). Anal. Calcd for C9H14N4O6 (274.24): C, 39.42; H, 5.15; N,
20.43. Found: C, 39.34; H, 5.05; N, 20.55.
0
0
0
0
177 °C; [
a
]
D = ꢁ36 (c 0.23, CHCl3); 1H NMR (CDCl3): d (ppm) 7.45–
7.23 (6H, m, aromatics, triazole H), 5.88 (1H, d, J1 ,2 9.2 Hz, H-10),
0
0
5.39–5.42 (2H, m, H-20, H-30), 5.24 (1H, pseudot, J3 ,4 9.2, Hz, J4 ,5
0
0
0
0
9.2 Hz, H-40), 4.28 (1H, dd, J6 a,6 b 11.9 Hz, H-60a), 4.14–4.09 (3H,
0
0
m, H-60b, CH2), 3.99 (1H, ddd, J5 ,6 a 5.3 Hz, J5 ,6 b 2.6 Hz, H-50), 2.05
(6H, s, 2 ꢃ CH3), 2.01, 1.85 (6H, 2s, 2 ꢃ CH3); 13C NMR (CDCl3): d
(ppm) 170.4, 169.8, 169.2, 168.8 (CO), 148.2 (triazole C-4), 138.4,
128.5, 128.5,128.5, 128.5, 126.5 (aromatics), 119.7 (triazole C-5),
85.5 (C-10), 74.9, 72.5, 70.1, 67.6 (C-20–C-50), 61.4 (C-60), 31.9
(CH2), 20.4 (2), 19.9 (2) (CH3). Anal. Calcd for C23H27N3O9
(489.49): C, 56.44; H, 5.56; N, 8.58. Found: C, 56.28; H, 5.64; N, 8.39.
0
0
0
0
4.17. 1-(b-D-Glucopyranosyl)-4-phenyl-1,2,3-triazole (3c)
From 2c (0.25 g, 0.53 mmol) according to General procedure IV.
Yield: 0.14 g (89%) white solid. Mp: 229–231 °C (lit.39 Mp: 228–
230 °C, lit.58 mp 234 °C); [
a
]
D = ꢁ69 (c 0.24, DMSO) (lit.58
[a]D = 0
(c 1, water)); 1H and 13C NMR data correspond to the reported
spectra.39
4.13. 1-(b-D-Glucopyranosyl)-4-hydroxymethyl-1,2,3-triazole
(3a)
4.18. 1-(b-D-Glucopyranosyl)-4-(2-naphthyl)-1,2,3-triazole (3d)
From 2a (0.25 g, 0.58 mmol) according to General procedure IV.
Yield: 0.13 g (82%) white solid. Mp: 156–158 °C (lit.32 mp: 162–
From 2d (0.16 g, 0.30 mmol) according to General procedure IV.
Yield: 0.08 g (72%) white solid. Mp: 212–214 °C; [ D = ꢁ26 (c 0.21,
a
]

Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
1177
DMSO); 1H NMR (DMSO-d6): d (ppm) 8.98 (1H, s, triazole H), 8.47
(1H, s, aromatic), 8.01–7.92 (4H, m, aromatics), 7.53 (2H, m, aro-
solid. Mp: 145–147 °C; [
a
]
D = +227 (c 0.21, CHCl3); 1H NMR
0
0
(CDCl3): d (ppm) 8.20 (1H, s, triazole H), 6.42 (1H, d, J1 ,2 6.6 Hz,
matics), 5.62 (1H, d, J1 ,2 7.9 Hz, H-10), 5.50 (1H, d, J 4.0 Hz, OH),
5.38 (1H, d, J 2.6 Hz, OH), 5.22 (1H, d, J 4.0 Hz, OH), 4.68 (1H, t,
OH), 3.84–3.29 (6H, m, H-20, H-30, H-40, H-50, H-60a, H-60b). 13C
NMR (DMSO-d6): d (ppm) 146.3 (triazole C-4), 133.1, 132.5,
128.5, 128.0, 127.9, 127.7, 126.6, 126.1, 123.6, 123.4 (aromatics),
120.8 (triazole C-5), 87.7 (C-10), 79.9, 76.8, 72.2, 69.6 (C-20–C-50),
60.7 (C-60). Anal. Calcd for C18H19N3O5 (357.37): C, 60.50; H,
5.36; N, 11.76. Found: C, 60.61; H, 5.31; N, 11.82.
H-10), 6.21 (1H, pseudot, J3 ,4 9.2 Hz, H-30), 5.34 (1H, dd, J2 ,3
0
0
0
0
0
0
9.2 Hz, H-20), 5.27 (1H, pseudot, J4 ,5 9.2 Hz, H-40), 4.43 (2H, q, J
0
0
7.3 Hz, CH2), 4.31 (1H, ddd, J5 ,6 a 4.0 Hz, H-50), 4.25 (1H, dd, J6 a,6 b
0
0
0
0
11.9 Hz, H-60a), 4.00 (1H, dd, J5 ,6 b 2.6 Hz, H-60b), 2.08 (6H, s,
2 ꢃ CH3), 2.04, 1.88 (6H, 2s, 2 ꢃ CH3), 1.43 (3H, t, J 7.3 Hz, CH3);
13C NMR (CDCl3): d (ppm) 170.4, 170.0, 169.6, 169.5 (CO), 160.2
(COOEt), 139.8 (triazole C-4), 129.6 (triazole C-5), 81.9 (C-10),
71.4, 70.0, 69.5, 67.6 (C-20–C-50), 61.6, 61.1 (C-60, CH2), 20.6 (3),
20.2 (CH3), 14.2 (CH3). Anal. Calcd for C19H25N3O11 (471.42): C,
48.41; H, 5.35; N, 8.91. Found: C, 48.60; H, 5.22; N, 8.83.
0
0
4.19. 1-(b-D-Glucopyranosyl)-4-(1-naphthyl)-1,2,3-triazole (3e)
From 2e (0.16 g, 0.30 mmol) according to General procedure IV.
Yield: 0.10 g (95%) colourless syrup. Rf: 0.35 (8:2 CHCl3–MeOH);
4.23. 1-(20,30,40,60-Tetra-O-acetyl-
a-D-glucopyranosyl)-4-phenyl-
1,2,3-triazole (5c)
[
a]
D = ꢁ22 (c 0.21, MeOH); 1H NMR (CD3OD): d (ppm) 8.48 (1H,
s, triazole H), 8.20–8.17 (1H, m, aromatic), 7.87–7.85 (2H, m, aro-
From 4 (0.2 g, 0.54 mmol) and phenylacetylene (0.06 mL,
matics), 7.63–7.61 (1H, m, aromatic), 7.49–7.44 (3H, m, aromatics),
0.54 mmol) according to General procedure II. Purified by column
5.75 (1H, d, J1 ,2 9.2 Hz, H-10), 4.05 (1H, pseudot, J2 ,3 9.2 Hz, H-20),
chromatography (1:2 EtOAc–hexane) to yield 0.10 g (39%) white
0
0
0
0
3.91 (1H, dd, J6 a,6 b 11.9 Hz, J5 ,6 a <1 Hz, H-60a), 3.73 (1H, dd, J5 ,6 b
5.3 Hz, H-60b), 3.68–3.55 (3H, m, H-30, H-40, H-50). 13C NMR
(CD3OD): d (ppm) 147.5 (triazole C-4), 135.3, 132.3, 130.3, 129.5,
128.5, 127.8, 127.2, 126.4, 126.2 (aromatics), 124.5 (triazole C-5),
89.8 (C-10), 81.1, 78.4, 74.0, 70.8 (C-20–C-50), 62.3 (C-60). Anal. Calcd
for C18H19N3O5 (357.37): C, 60.50; H, 5.36; N, 11.76. Found: C,
60.42; H, 5.25; N, 11.69.
solid. Mp: 193–195 °C; [
d (ppm) 8.04 (1H, s, triazole H), 7.87–7.85 (2H, m, aromatics), 7.49–
a]
D = +282 (c 0.21, CHCl3); 1H NMR (CDCl3):
0
0
0
0
0
0
7.38 (3H, m, aromatics), 6.48 (1H, d, J1 ,2 6.6 Hz, H-10), 6.34 (1H,
0
0
pseudot, J3 ,4 9.2 Hz, H-30), 5.39 (1H, dd, J2 ,3 9.2 Hz, H-20), 5.30
0
0
0
0
(1H, pseudot, J4 ,5 9.2 Hz, H-40), 4.39 (1H, ddd, J5 ,6 a 4.0 Hz, H-50),
0
0
0
0
4.28 (1H, dd, J6 a,6 b 11.9 Hz, H-60a), 4.06 (1H, dd, J5 ,6 b 2.6 Hz, H-
60b), 2.08 (6H, s, 2 ꢃ CH3), 2.06, 1.89 (6H, 2s, 2 ꢃ CH3); 13C NMR
(CDCl3): d (ppm) 170.6, 170.2, 169.7 (2) (CO), 147.1 (triazole C-4),
129.2, 128.8 (2), 128.5, 125.5 (2) (aromatics), 121.9 (triazole C-5),
81.2 (C-10), 70.8, 70.3, 69.5, 67.8 (C-20–C-50), 61.1 (C-60), 20.3 (3),
20.0 (CH3). Anal. Calcd for C22H25N3O9 (475.46): C, 55.58; H, 5.30;
N, 8.84. Found: C, 55.45; H, 5.18; N, 9.01.
0
0
0
0
4.20. 1-(b-D-Glucopyranosyl)-4-benzyl-1,2,3-triazole (3f)
From 2f (0.25 g, 0.51 mmol) according to General procedure IV.
Yield: 0.16 g (95%) colourless syrup. Rf: 0.39 (8:2 CHCl3–MeOH);
[
a
]
D = ꢁ18 (c 0.23, DMSO); 1H NMR (CD3OD): d (ppm) 7.89 (1H,
0
0
s, triazole H), 7.26–7.19 (5H, m, aromatics), 5.56 (1H, d, J1 ,2
4.24. 1-(
(6a)
a-D-Glucopyranosyl)-4-hydroxymethyl-1,2,3-triazole
9.2 Hz, H-10), 4.05 (2H, s, CH2), 3.87–3.84 (2H, m, H-20, H-60a,),
3.69 (1H, dd, J6 a,6 b 11.9 Hz, J5 ,6 b <1 Hz, H-60b), 3.54–3.48 (3H, m,
H-30, H-40, H-50). 13C NMR (DMSO-d6): d (ppm) 145.9 (triazole C-
4), 139.5, 128.6 (2), 128.4 (2), 126.2 (aromatics), 121.4 (triazole
C-5), 87.6 (C-10), 79.9, 76.7, 72.2, 69.7 (C-20–C-50), 60.8 (C-60),
31.3 (CH2). Anal. Calcd for C15H19N3O5 (321.34): C, 56.07; H,
5.96; N, 13.08. Found: C, 55.92; H, 6.09; N, 12.95.
0
0
0
0
From 5a (0.1 g, 0.23 mmol) according to General procedure IV.
Yield 0.04 g (72%) pale yellow syrup. Rf: 0.44 (1:1 CHCl3–MeOH);
[a]
D = +82 (c 0.20, H2O); 1H NMR (D2O): d (ppm) 8.10 (1H, s, tria-
zole H), 6.26 (1H, d, J1 ,2 5.3 Hz, H-10), 4.70 (2H, s, CH2), 4.38 (1H,
0
0
pseudot, J3 ,4 9.2 Hz, H-30), 4.09 (1H, dd, J2 ,3 9.2 Hz, H-20), 3.73–
0
0
0
0
3.64 (3H, m, H-50, H-60a, H-60b), 3.54 (1H, pseudot, J4 ,5 9.2 Hz, H-
40); 13C NMR (D2O): d (ppm) 146.3 (triazole C-4), 126.3 (triazole
C-5), 85.3 (C-10), 75.4, 73.3, 70.4, 69.5 (C-20–C-50), 60.5 (C-60),
54.6 (CH2). Anal. Calcd for C9H15N3O6 (261.24): C, 41.38; H, 5.79;
N, 16.09. Found: C, 41.25; H, 5.88; N, 16.17.
0
0
4.21. 1-(20,30,40,60-Tetra-O-acetyl-
hydroxymethyl-1,2,3-triazole (5a)
a-D-glucopyranosyl)-4-
From
4 (1 g, 2.68 mmol) and propargyl alcohol (0.16 mL,
2.70 mmol) according to General procedure II. Purified by column
chromatography (3:1 EtOAc–hexane) to yield 0.41 g (36%) colour-
4.25. Methyl 1-(a-D-glucopyranosyl)-1,2,3-triazole-4-
less syrup. Rf: 0.18 (3:1 EtOAc–hexane); [
a]D = +236 (c 0.22, CHCl3);
carboxylate (6bii)
1H NMR (CDCl3): d (ppm) 7.77 (1H, s, triazole H), 6.41 (1H, d, J1 ,2
0
0
5.3 Hz, H-10), 6.28 (1H, pseudot, J3 ,4 10.6 Hz, H-30), 5.35 (1H, dd,
From 5b (0.25 g, 0.53 mmol) according to General procedure IV.
Yield 0.14 g (93%) white solid. Mp: 174–176 °C; [ D = +68 (c 0.21,
H2O); 1H NMR (D2O): d (ppm) 8.69 (1H, s, triazole H), 6.32 (1H, d,
0
0
J2 ,3 9.2 Hz, H-20), 5.28 (1H, pseudot, J4 ,5 9.2 Hz, H-40), 4.84 (2H,
a]
0
0
0
0
s, CH2) 4.36 (1H, ddd, J5 ,6 a 4.0 Hz, H-50), 4.27 (1H, dd, J6 a,6 b
0
0
0
0
11.9 Hz, H-60a), 4.01 (1H, dd, J5 ,6 b 2.6 Hz, H-60b), 3.72 (1H, s,
CH2OH), 2.08 (6H, s, 2 ꢃ CH3), 2.04, 1.89 (6H, 2s, 2 ꢃ CH3); 13C
NMR(CDCl3): d (ppm) 170.4, 170.1 169.7, 169.6 (CO), 147.3 (tria-
zole C-4), 124.2 (triazole C-5), 81.3 (C-10), 70.9, 70.3, 69.5, 67.8
(C-20–C-50), 61.1 (C-60), 55.9 (CH2), 20.6 (2), 20.3, 20.2 (CH3). Anal.
Calcd for C17H23N3O10 (429.39): C, 47.55; H, 5.40; N, 9.79. Found: C,
47.40; H, 5.47; N, 9.64.
J1 ,2 5.3 Hz, H-10), 4.36 (1H, pseudot, J3 ,4 9.2 Hz, H-30), 4.10 (1H, dd,
0
0
0
0
0
0
J2 ,3 9.2 Hz, H-20), 3.91 (1H, s, OMe), 3.79–3.67 (3H, m, H-50, H-60a,
0
0
H-60b), 3.57 (1H, pseudot, J4 ,5 9.2 Hz, H-40); 13C NMR (D2O): d
(ppm) 162.9 (CO), 139.2 (triazole C-4), 132.0 (triazole C-5), 86.4
(C-10), 76.3, 73.6, 70.8, 69.9 (C-20–C-50), 61.0 (C-60), 51.4 (OMe).
Anal. Calcd for C10H15N3O7 (289.25): C, 41.53; H, 5.23; N, 14.53.
Found: C, 41.41; H, 5.32; N, 14.60.
0
0
4.22. Ethyl 1-(20,30,40,60-tetra-O-acetyl-
a-
D-glucopyranosyl)-
4.26. Sodium 1-(a-D-glucopyranosyl)-1,2,3-triazole-4-
1,2,3-triazole-4-carboxylate (5b)
carboxylate (6biii)
From
4
(1 g, 2.70 mmol) and ethyl propiolate (0.28 mL,
From 5b (0.4 g, 0.85 mmol) according to General procedure V.
2.70 mmol) according to General procedure II. Purified by column
Purified by column chromatography (3:7 CHCl3–MeOH) to yield
chromatography (4:6 EtOAc–hexane) to yield 0.91 g (72%) white
0.12 g (47%) white solid. Mp: 190–192 °C; [a]D = +143 (c 0.19,

1178
Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
H2O); 1H NMR (D2O): d (ppm) 8.33 (1H, s, triazole H), 6.25 (1H, d,
azole H), 8.09–7.23 (20H, m, aromatics), 7.08 (1H, s, CONH2), 6.58
J1 ,2 6.6 Hz, H-10), 4.38 (1H, pseudot, J3 ,4 9.2 Hz, H-30), 4.07 (1H, dd,
(1H, s, CONH2), 6.33 (1H, pseudot, J4 ,5 7.9 Hz, H-40), 6.19 (1H, d,
0
0
0
0
0
0
J2 ,3 9.2 Hz, H-20), 3.74–3.63 (3H, m, H-50, H-60a, H-60b), 3.54 (1H,
J3 ,4 7.9 Hz, H-30), 5.89 (1H, pseudot, J5 ,6 10.6 Hz, H-50), 5.20 (1H,
0
0
0
0
0
0
pseudot, J4 ,5 9.2 Hz, H-40); 13C NMR (D2O): d (ppm) 168.1 (CO),
144.7 (triazole C-4), 129.9 (triazole C-5), 85.7 (C-10), 75.8, 73.6,
70.8, 69.9 (C-20–C-50), 60.9 (C-60).
ddd, J6 ,7a 2.6 Hz, H-60), 4.89 (1H, dd, J7 a,7 b 11.9 Hz, H-70a), 4.57
0
0
0
0
0
0
(1H, dd, J6 ,7b 4.0 Hz, H-70b), 4.32 (2H, q, J 7.3 Hz, CH2), 1.32 (3H,
t, J 7.3 Hz, CH3). 13C NMR (CDCl3): d (ppm) 166.1, 165.6, 165.0,
164.9, 164.2, 159.9 (CO), 139.9 (triazole C-4), 133.8–128.0 (aromat-
ics), 126.6 (triazole C-5), 89.6 (C-20), 74.1, 72.2, 70.9, 68.0 (C-30–C-
60), 62.3, 61.4 (C-70, CH2), 14.1 (CH3). Anal. Calcd for C40H34N4O12
(762.74): C, 62.99; H, 4.49; N, 7.35. Found: C, 63.08; H, 4.57; N,
7.21.
0
0
4.27. 1-(a-D-Glucopyranosyl)-1,2,3-triazole-4-carboxamide
(6biv)
5b (0.4 g, 0.85 mmol) was stirred in dry methanolic NH3 (4 mL)
at rt for 1 day. After completion of the reaction (monitored by TLC
7:3 CHCl3–MeOH), the solvent was removed to give white crystal-
4.31. [1-(30,40,50,70-Tetra-O-benzoyl-b-
ulopyranosyl)-4-phenyl-1,2,3-triazole]onamide (9c)
D-gluco-hept-2-
line product. Yield: 0.19 g (81%). Mp: 219–221 °C [
a]D = +208 (c
0.21, H2O)); 1H NMR (D2O): d (ppm) 8.59 (1H, s, triazole H), 6.34
(1H, d, J1 ,2 5.3 Hz, H-10), 4.40 (1H, pseudot, J3 ,4 9.2 Hz, H-30),
From 7 (0.1 g, 0.15 mmol) and phenylacetylene (33 lL,
0.30 mmol) according to General procedure III. Purified by column
0
0
0
0
4.14 (1H, dd, J2 ,3 9.2 Hz, H-20), 3.81–3.67 (3H, m, H-50, H-60a, H-
0
0
60b), 3.60 (1H, pseudot, J4 ,5 9.2 Hz, H-40); (DMSO-d6): d (ppm)
7.90 (1H, s, CONH2), 7.50 (1H, s, CONH2). 13C NMR (D2O): d (ppm)
164.7 (CO), 141.7 (triazole C-4), 130.1 (triazole C-5), 86.2 (C-10),
76.1, 73.6, 70.8, 69.9 (C-20–C-50), 60.9 (C-60). Anal. Calcd for
C9H14N4O6 (274.24): C, 39.42; H, 5.15; N, 20.43. Found: C, 39.51;
H, 5.23; N, 20.31.
chromatography (1:2 EtOAc–hexane) to yield 0.07 g (conversion:
0
0
73%, yield: 83%) white solid. Mp: 193–195 °C; [
a
]
D = ꢁ198 (c
0.22, CHCl3); 1H NMR (CDCl3): d (ppm) 8.22 (1H, s, triazole H),
8.13–7.12 (26H, m, aromatics + CONH2), 6.33–6.29 (2H, m, H-
40 + CONH2), 6.24 (1H, d, J3 ,4 7.9 Hz, H-30), 5.92 (1H, pseudot, J4 ,5
0
0
0
0
7.9 Hz, J5 ,6 9.2 Hz, H-50), 5.29 (1H, ddd, J6 ,7a 2.6 Hz, H-60), 5.00
0
0
0
0
(1H, dd, J7 a,7 b 13.2 Hz, H-70a), 4.54 (1H, dd, J6 ,7 b 4.0 Hz, H-70b);
13C NMR (CDCl3): d (ppm) 166.4, 166.2, 165.0, 164.9, 164.2 (CO),
147.6 (triazole C-4), 133.7–125.7 (aromatics), 118.6 (triazole C-
5), 89.4 (C-20), 74.0, 72.2, 71.0, 68.9 (C-30–C-60), 62.2 (C-70). Anal.
Calcd for C43H34N4O10 (766.77): C, 67.36; H, 4.47; N, 7.31. Found:
C, 67.25; H, 4.39; N, 7.42.
0
0
0
0
4.28. 1-(a-D-Glucopyranosyl)-4-phenyl-1,2,3-triazole (6c)
From 5c (0.075 g, 0.16 mmol) according to General procedure
IV. Yield 0.04 g (75%) white solid. Mp: 195–197 °C; [a]D = +143 (c
0.23, H2O); 1H NMR (D2O–CD3OD): d (ppm) 8.38(1H, s, triazole
H), 7.74–7.72 (2H, m, aromatics), 7.44–7.33 (3H, m, aromatics),
6.25 (1H, d, J1 ,2 6.6 Hz, H-10), 4.39 (1H, pseudot, J3 ,4 9.2 Hz, H-
4.32. [1-(30,40,50,70-Tetra-O-benzoyl-b-
D-gluco-hept-2-
ulopyranosyl)-4-(2-naphthyl)-1,2,3-triazole]onamide (9d)
0
0
0
0
30), 4.06 (1H, dd, J2 ,3 9.2 Hz, H-20), 3.73–3.65 (3H, m, H-50, H-60a,
0
0
H-60b), 3.52 (1H, pseudot, J4 ,5 9.2 Hz, H-40); 13C NMR (D2O–
CD3OD): d (ppm) 147.6 (triazole C-4), 130.3, 130.2 (2), 129.9,
126.8 (2) (aromatics), 125.0 (triazole C-5), 86.3 (C-10), 76.4, 74.2,
71.4, 70.4 (C-20–C-50), 61.4 (C-60). Anal. Calcd for C14H17N3O5
(307.31): C, 54.72; H, 5.58; N, 13.67. Found: C, 54.80; H, 5.74; N,
13.55.
0
0
From 7 (0.1 g, 0.15 mmol) and 2-naphthylacetylene (0.047 g,
0.30 mmol) according to General procedure III. Purified by column
chromatography (4:6 EtOAc–hexane) to yield 0.068 g (Conversion:
63%, Yield: 87%) white solid. Mp: 242–243 °C; [
a
]
D = ꢁ289 (c 0.23,
CHCl3); 1H NMR (CDCl3): d (ppm) 8.34 (1H, s, triazole H), 8.15–7.14
(28H, m, aromatics + CONH2), 6.36–6.28 (3H, m, H-30, H-
4.29. [1-(30,40,50,70-Tetra-O-benzoyl-b-
ulopyranosyl)-4-hydroxymethyl-1,2,3-triazole]onamide (9a)
D
-gluco-hept-2-
40 + CONH2), 5.94 (1H, pseudot, J4 ,5 7.9 Hz, J5 ,6 9.2 Hz, H-50), 5.31
0
0
0
0
(1H, ddd, J6 ,7a 2.6 Hz, H-60), 5.03 (1H, dd, J7 a,7 b 11.9 Hz, H-70a),
0
0
0
0
4.57 (1H, dd, J6 ,7 b 4.0 Hz, H-70b). 13C NMR (CDCl3): d (ppm)
166.5, 166.2, 165.0, 164.9, 164.2 (CO), 147.6 (triazole C-4),
133.7–123.6 (aromatics), 118.9 (triazole C-5), 89.5 (C-20), 74.0,
72.3, 71.1, 68.2 (C-30–C-60), 62.3 (C-70). Anal. Calcd for
C47H36N4O10 (816.83): C, 69.11; H, 4.44; N, 6.86. Found: C, 69.25;
H, 4.51; N, 6.97.
0
0
From
7 (0.1 g, 0.15 mmol) and propargyl alcohol (18 lL,
0.30 mmol) according to General procedure III. Purified by column
chromatography (6:4 EtOAc–hexane) to yield 0.041 g (conversion:
51%, yield: 75%) white solid. Mp: 112–114 °C; [a]D = +0.2 (c 0.20,
CHCl3); 1H NMR (CDCl3): d (ppm) 8.04–7.22 (21H, m, aromat-
ics + triazole H), 7.09 (1H, s, CONH2), 6.53 (1H, s, CONH2), 6.34
(1H, pseudot, J4 ,5 7.9 Hz, H-40), 6.17 (1H, d, J3 ,4 7.9 Hz, H-30),
4.33. Methyl [1-(30,40,50,70-tetra-O-benzoyl-b-
ulopyranosyl)-4-ethoxycarbonyl-1,2,3-triazole]onate (10b)
D-gluco-hept-2-
0
0
0
0
5.87 (1H, pseudot, J5 ,6 7.9 Hz, H-50), 5.08 (1H, ddd, J6 ,7a 2.6 Hz,
0
0
0
0
J6 ,7b 4.0 Hz, H-60), 4.82 (1H, dd, J7 a,7 b 11.9 Hz, H-70a), 4.53–4.49
(3H, m, H-70b + CH2), 3.61 (1H, s, CH2OH). 13C NMR (CDCl3): d
(ppm) 166.2 (2), 165.1, 164.9, 164.4 (CO), 147.6 (triazole C-4),
133.7–128.2 (aromatics), 120.9 (triazole C-5), 89.4 (C-20), 73.7,
72.1, 71.1, 68.3 (C-30–C-60), 62.5 (C-70), 55.7 (CH2). Anal. Calcd for
C38H32N4O11 (720.70): C, 63.33; H, 4.48; N, 7.77. Found: C, 63.21;
H, 4.55; N, 7.70.
0
0
0
0
From
8 (0.6 g, 0.88 mmol) and ethyl propiolate (0.09 mL,
0.88 mmol) according to General procedure II. Purified by column
chromatography (1:3 EtOAc–hexane) to yield 0.36 g (Conversion:
74%, Yield: 70%) pale yellow syrup. Rf: 0.29 (1:2 EtOAc–hexane);
[a]
D = +46 (c 0.24, CHCl3); 1H NMR (CDCl3): d (ppm) 8.54 (1H, s, tri-
0
0
azole H), 8.08–7.23 (20H, m, aromatics), 6.47 (1H, pseudot, J4 ,5
9.2 Hz, H-40), 6.39 (1H, d, J3 ,4 7.9 Hz, H-30), 5.91 (1H, pseudot, J5 ,6
0
0
0
0
4.30. [1-(30,40,50,70-Tetra-O-benzoyl-b-
ulopyranosyl)-4-ethoxycarbonyl-1,2,3-triazole]onamide (9b)
D
-gluco-hept-2-
9.2 Hz, H-50), 4.93 (1H, ddd, J6 ,7a 2.6 Hz, H-60), 4.87 (1H, dd, J7 a,7 b
0
0
0
0
11.9 Hz, H-70a), 4.59 (1H, dd, J6 ,7b 4.0 Hz, H-70b), 4.37 (2H, q, J
7.3 Hz, CH2), 3.88 (3H, s, OMe), 1.35 (3H, t, J 7.3 Hz, CH3). 13C NMR
(CDCl3): d (ppm) 165.8, 164.9, 164.8, 164.3, 164.1, 160.0 (CO),
139.5 (triazole C-4), 133.4–128.1 (aromatics), 126.2 (triazole C-5),
89.7 (C-20), 73.9, 71.3, 70.7, 68.0 (C-30–C-60), 62.1, 61.2 (C-70, CH2),
54.0 (OMe), 14.0 (CH3). Anal. Calcd for C41H35N3O13 (777.75): C,
63.32; H, 4.54; N, 5.40. Found: C, 63.45; H, 4.59; N, 5.32.
0
0
From
7 (0.7 g, 1.07 mmol) and ethyl propiolate (0.11 mL,
1.07 mmol) according to General procedure II. Purified by column
chromatography (1:2 EtOAc–hexane) to yield 0.28 g (conversion:
63%, yield: 56%) pale yellow syrup. Rf: 0.31 (1:1 EtOAc–hexane);
[a
]
D = ꢁ70 (c 0.17, CHCl3); 1H NMR (CDCl3): d (ppm) 8.56 (1H, s, tri-

Éva Bokor et al. / Bioorg. Med. Chem. 18 (2010) 1171–1180
1179
4.34. [1-(b-
1,2,3-triazole]onamide (11a)
D
-Gluco-hept-2-ulopyranosyl)-4-hydroxymethyl-
H2O); 1H NMR (D2O): d (ppm) 8.39 (1H, s, triazole H), 3.89–3.82
(4H, m, H-30, H-60, H-70a, H-70b), 3.68–3.63 (2H, m, H-40, H-50).
13C NMR (D2O): d (ppm) 170.2, 168.0 (CO), 145.0 (triazole C-4),
126.2 (triazole C-5), 90.8 (C-20), 77.6, 76.5, 75.3, 69.3 (C-30–C-60),
60.9 (C-70).
From 9a (0.14 g, 0.19 mmol) according to General procedure IV.
Purified by column chromatography (7:3 CHCl3–MeOH) to yield
0.04 g (68%) colourless syrup. Rf: 0.40 (1:1 CHCl3–MeOH);
[
a]
D = +124 (c 0.17, H2O); 1H NMR (D2O): d (ppm) 8.27 (1H, s, tria-
4.39. Enzymology
zole H), 4.72 (1H, s, CH2), 4.01 (1H, d, J3 ,4 10.6 Hz, H-30), 3.92–3.81
(3H, m, H-60, H-70a, H-70b), 3.80–3.65 (2H, m, H-40, H-50). 13C NMR
(D2O): d (ppm) 168.7 (CO), 147.4 (triazole C-4), 123.0 (triazole C-5),
90.3 (C-20), 78.1, 76.1, 74.3, 69.2 (C-30–C-60), 60.9 (C-70), 55.3 (CH2).
Anal. Calcd for C10H16N4O7 (304.26): C, 39.48; H, 5.30; N, 18.41.
Found: C, 39.41; H, 5.41; N, 18.50.
0
0
Glycogen phosphorylase b was prepared from rabbit skeletal
muscle according to the method of Fischer and Krebs,60 using dithi-
othreitol instead of L-cysteine, and recrystallised at least three
times before use. Kinetic experiments were performed in the direc-
tion of glycogen synthesis as described previously.61 Kinetic data
for the inhibition of rabbit skeletal muscle glycogen phosphorylase
4.35. Sodium [1-(b-
D
-gluco-hept-2-ulopyranosyl)onamide]-
were collected using different concentrations of a-D-glucose-1-
1,2,3-triazole-4-carboxylate (11b)
phosphate (2–20 mM), constant concentrations of glycogen (1%
w/v) and AMP (1 mM), and various concentrations of inhibitors.
Inhibitors were dissolved in dimethyl sulfoxide (DMSO) and di-
luted in the assay buffer (50 mM triethanolamine, 1 mM EDTA
and 1 mM dithiothreitol) so that the DMSO concentration in the as-
say should be lower than 1%. The enzymatic activities were pre-
sented in the form of double-reciprocal plots (Lineweaver–Burk)
applying a nonlinear data analysis program. The inhibitor con-
stants (Ki) were determined by Dixon plots, by replotting the
slopes from the Lineweaver–Burk plots against the inhibitor con-
centrations.15,49 The means of standard errors for all calculated ki-
netic parameters averaged to less than 10%.
From 9b (0.25 g, 0.33 mmol) according to General procedure V.
Purified by column chromatography (3:7 CHCl3–MeOH) to yield
0.075 g (67%) white solid. Mp: 275–278 °C; [
a]D = +76 (c 0.24,
H2O); 1H NMR (D2O): d (ppm) 8.48 (1H, s, triazole H), 3.99 (1H,
d, J3 ,4 9.2 Hz, H-30), 3.91–3.87 (2H, m, H-60, H-70a), 3.82 (1H, dd,
0
0
J7 a,7 b 13.2 Hz, J6 ,7 b 2.6 Hz, H-70b), 3.73–3.63 (2H, m H-40, H-50).
13C NMR (D2O): d (ppm) 168.5, 167.7 (CO), 145.5 (triazole C-4),
126.0 (triazole C-5), 90.3 (C-20), 78.0, 76.1, 74.2, 69.1 (C-30–C-60),
60.8 (C-70).
0
0
0
0
4.36. [1-(b-D-Gluco-hept-2-ulopyranosyl)-4-phenyl-1,2,3-
triazole]onamide (11c)
Acknowledgement
From 9c (0.23 g, 0.30 mmol) according to General procedure IV.
Purified by column chromatography (8:2 CHCl3–MeOH) to yield
0.097 g (92%) colourless syrup. Rf: 0.22 (8:2 CHCl3–MeOH);
This work was supported by the Hungarian Scientific Research
Fund (Grants: OTKA 61336, 68578, and 77712).
[a]
D = +85 (c 0.20, H2O); 1H NMR (D2O): d (ppm) 8.44 (1H, s, tria-
References and notes
zole H), 7.63–7.59 (2H, m, aromatics), 7.35–7.31 (3H, m, aromat-
ics), 4.02 (1H, d, J3 ,4 9.2 Hz, H-30), 3.92–3.79 (3H, m, H-60, H-70a,
H-70b), 3.72 (1H, pseudot, J 9.2, 9.2 Hz, H-40 or H-50), 3.65 (1H,
pseudot, J 9.2, 9.2 Hz, H-40 or H-50); 13C NMR (D2O): d (ppm)
168.6 (CO), 148.1 (triazole C-4), 129.8 (2), 129.7, 129.4, 126.4 (2)
(aromatics), 120.9 (triazole C-5), 90.3 (C-20), 78.2, 76.1, 74.4, 69.3
(C-30–C-60), 61.0 (C-70). Anal. Calcd for C15H18N4O6 (350.33): C,
51.43; H, 5.18; N, 15.99. Found: C, 51.34; H, 5.11; N, 16.07.
0
0
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Hayes, J. M.; Tiraidis, C.; Lazoura, E.; Leonidas, D. D.; Zographos, S. E.;
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4.37. [1-(b-D-Gluco-hept-2-ulopyranosyl)-4-(2-naphthyl)-1,2,3-
triazole]onamide (11d)
10. Somsák, L.; Nagy, V.; Hadady, Z.; Docsa, T.; Gergely, P. Curr. Pharm. Des. 2003, 9,
1177.
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From 9d (0.24 g, 0.29 mmol) according to General procedure IV.
Purified by column chromatography (8:2 CHCl3–MeOH) to yield
0.096 g (81%) white solid. Mp: 220–222 °C; [a]D = +66 (c 0.23,
MeOH); 1H NMR (CD3OD): d (ppm) 8.79 (1H, s, triazole H), 8.34
(1H, s, aromatic), 7.93–7.85 (4H, m, aromatics), 7.49–7.47 (2H, m,
aromatics), 4.10 (1H, d, J3 ,4 9.2 Hz, H-30), 3.97 (1H, dd, J7a ,7b
0
0
0
0
13.2 Hz, J6 ,7 a <1 Hz, H-70a), 3.86–3.76 (3H, m, H-40 or H-50, H-60,
H-70b), 3.66 (1H, pseudot, J 9.2, 9.2 Hz, H-40 or H-50); 13C NMR
(CD3OD): d (ppm) 169.3 (CO), 148.7 (triazole C-4), 135.1, 134.8,
129.8, 129.2, 128.9, 127.6, 127.4, 125.6, 125.5, 124.7 (aromatics),
121.3 (triazole C-5), 90.8 (C-20), 79.5, 77.5, 76.0, 70.4 (C-30–C-60),
62.2 (C-70). Anal. Calcd for C19H20N4O6 (400.39): C, 57.00; H,
5.03; N, 13.99. Found: C, 56.88; H, 5.11; N, 13.90.
0
0
14. Watson, K. A.; Mitchell, E. P.; Johnson, L. N.; Cruciani, G.; Son, J. C.; Bichard, C. J.
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}
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4861.
17. Chrysina, E. D.; Oikonomakos, N. G.; Zographos, S. E.; Kosmopoulou, M. N.;
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4.38. [1-(b-D-Gluco-hept-2-ulopyranosyl)-4-carboxylato-1,2,3-
triazole]onic acid disodium salt (12b)
From 10b (0.26 g, 0.33 mmol) according to General procedure V.
Purified by column chromatography (3:7 CHCl3–MeOH) to yield
0.04 g (35%) white solid. Mp: 230–232 °C; [a]D = +49 (c 0.21,

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