A facile synthesis, structure, and antimicrobial evaluation of novel 4-arylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-3-ones, their N- and N,O-bis-β-d-glucosides

Article abstract of DOI:10.1016/j.carres.2009.06.003

Synthesis of some novel 4-arylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-3-ones, their N- and N,O-bis- β-d-glucosides is described. Antimicrobial evaluation of eight selected compounds against Aspergillus fumigatus RCMB 002008 (1), Penicillium italicu

Full text of DOI:10.1016/j.carres.2009.06.003

Carbohydrate Research 344 (2009) 1654–1659
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Carbohydrate Research
journal homepage: www.elsevier.com/locate/carres
A facile synthesis, structure, and antimicrobial evaluation of novel
4-arylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-3-ones,
their N- and N,O-bis-b-D-glucosides
Nasser S. A. M. Khalil
Regional Center for Food and Feed, Agricultural Research Center, Giza, Egypt
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 4 April 2009
Received in revised form 1 June 2009
Accepted 2 June 2009
Available online 6 June 2009
Synthesis of some novel 4-arylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-3-ones, their N- and
N,O-bis- b-D-glucosides is described. Antimicrobial evaluation of eight selected compounds against
Aspergillus fumigatus RCMB 002008 (1), Penicillium italicum RCMB 001018 (1), Syncephalastrum racemo-
sum RCMB 016001, Candida albicans RCMB 005003, Staphylococcus aureus RCMB 106-001 (1), Pseudomo-
nas aeruginosa RCMB 102-002, Bacillus subtilis RCMB 101-001, and Escherichia coli RCMB 103-001 has
been achieved. The screening results indicated that all the tested compounds exhibited different inhibi-
tory effects against five to seven different organisms of the eight test organisms.
Keywords:
Synthesis
Glucosidation
Pyrazoles
Ó 2009 Elsevier Ltd. All rights reserved.
N-b-
D-Glucosides
N,O-Bis(b-
D-glucosides)
Antimicrobial activity
1. Introduction
interesting structural and spectroscopic properties which have
been the subject of many reports.24,25 Among these ligands, acyl
Fluorinated analogues of natural substances are mainly of inter-
est in bioorganic chemistry1 since single fluorine atoms or trifluo-
romethyl groups introduced in place of hydrogen atoms often
increase the biological activity of the parent compounds. The tri-
fluoromethyl-substituted compounds were found to possess bio-
logical activities as herbicides,2 fungicides,3 analgesic agents,4
antipyretic agents,5 and inhibitors for platelet aggregation.6
The chemistry of pyrazolone derivatives has attracted much
attention because of their interesting structural properties and
applications in diverse areas.7 Pyrazolone derivatives find potential
application in medicinal chemistry as analgesic,8 anti-inflamma-
tory,9 and therapeutic agents.10 As an example, edaravone
(3-methyl-1-phenyl-2-pyrazolin-5-one) has been recently shown
to produce marked attenuation of brain damage caused by ische-
mia-reperfusion,11 and its pharmacological actions were attributed
to its antioxidant activity, as a potent hydroxyl radical scavenger.12
Many pyrazolone derivatives are useful reagents for the extraction
and separation of various metal ions.13–17 They can also be used in
laser materials, as 1H NMR shift reagents, in chromatographic
study and in the petrochemical industry.18–22 Recently, photochro-
mism of pyrazolone derivatives has also been reported.23 Many of
these ligands exhibit tautomerism, and because of this they show
pyrazolones have been studied extensively owing to their effective
properties with respect to extracting metal ions.26,27 On the other
hand, arylhydrazonopyrazolone chemistry is less extensive. It has
been found that some pyrazole glycosides show anticancer and/
or antiviral activity, alone, or in combination with other drugs.28
Following the reported modified Hilbert-Johnson reaction,29
only few N-glucosyl derivatives of 4-arylhydrazono-5-trifluoro-
methyl-2,4-dihydropyrazol-3-ones30 have been synthesized via
coupling of the silylated pyrazole derivatives with the acylated glu-
cosyl halide in the presence of Friedel–Crafts catalyst. Recently, we
reported simple convenient base-induced glycosylation of different
heterocyclic systems, as a part of an ongoing program, directed for
preparation of bio-active molecules.31–44 Thus, the current work
describes simple synthetic approach as well as antimicrobial eval-
uation of some novel 4-arylhydrazono-5-trifluoromethyl-2,4-dihy-
dropyrazol-3-ones and their glucosides.
2. Results and discussion
2.1. Synthesis
Scheme 1 illustrates the synthetic route towards some novel
biologically active fluorinated pyrazoles. With this aim,
5-trifluoromethyl-2,4-dihydropyrazol-3-one (1) was coupled with
E-mail address: nasserkhalil_23@hotmail.com
0008-6215/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.carres.2009.06.003

N. S. A. M. Khalil / Carbohydrate Research 344 (2009) 1654–1659
1655
F3C
N
O
N
H
1
R
N2Cl
2a-d
R
R
R
N
F3C
HN
N
N
N
F3C
N
N
F3C
H
H
H
O
N
N
O
H
N
O
N
N
H
3a-d(III)
3a-d(I)
3a-d(II)
OAc
O
AcO
AcO
DMF/TEA
R
AcO
4
Br
R
OAc
N
N
F3C
O
N
N
F3C
AcO
AcO
N
H
N
O
N
O
AcO
OAc
N
O
OAc
O
OAc
AcO
AcO
5a-d
6a-d
AcO
OAc
OAc
NaOMe/MeOH
NaOMe/MeOH
R
R
OH
N
F3C
O
N
HO
HO
N
N
N
H
O
F3C
N
OH
OH
N
O
O
HO
N
O
2, 3, 5, 6
R
OH
7 (R= H)
HO
HO
HO
8 (R=H)
a
b
c
H
OH
OH
CH3
OCH3
Cl
d
Scheme 1.
aryldiazonium chlorides (2a–d), to give the new 4-arylhydrazono-
5-trifluoromethyl-2,4-dihydropyrazol-3-ones (3a–d). The molecu-
lar structures of these compounds are such that they can exist in
three possible tautomeric forms, namely, the hydrazo-keto form
3a–d (I), the hydrazo-enol form 3a–d (II), and the azo-enol form
3a–d (III). Detailed spectral and chemical studies were carried out
to prove their existence. Thus, the IR spectra of compounds 3a–d
showed two characteristic bands in the ranges 3171–3279 and
1662–1670 cmꢀ1, which are assigned to NH and C@O functions,
respectively, for the tautomeric hydrazo-keto form 3a–d (I). In solu-
tion, the 1H NMR spectra of compounds 3a–d were acquired in
CDCl3 and compared to those acquired for compounds 3a,b in
DMSO-d6 under the same conditions. In CDCl3, compounds 3a–d re-
vealed two signals at d 9.10–9.96 (s, 1H, D2O exchangeable) and
13.70–13.94 (br, 1H, D2O exchangeable), which can be assigned to
either the pyrazole NH and hydrazo NH functions, respectively, for
the tautomeric hydrazo-keto form 3a–d (I) or the pyrazole NH
and OH functions, respectively for the tautomeric hydrazo-enol
form 3a–d (II). In either case the hydrazo NH function of the tauto-
meric hydrazo-keto form 3a–d (I) and the OH function of hydrazo-
enol form 3a–d (II) are strongly deshielded because of the possible
hydrogen bonding. Thus, in CDCl3 and comparing with the solid
state study (IR) together with glucosidation study (discussed later),
it is preferred to assign the signal at d 13.70–13.94 (br) to hydrazo
NH of the hydrazo-keto form 3a–d (I). In DMSO-d6, the 1H NMR
spectra of compounds 3a–d showed two signals at 5.17 (br, D2O
exchangeable) and 12.55–12.58 (s, D2O exchangeable) which are as-
signed to the NH and OH functions, respectively, for the tautomeric
azo-enol form 3a–d (III). In this case, the OH function is strongly
deshielded because of the possible hydrogen bonding. The forma-
tion of the bis(glucosides) (6a–d) during glucosidation of com-
pounds 3a–d (discussed later) gave further evidence and
supported the possible existence of the tautomeric azo-enol form
3a–d (III) in solution.
Compounds 3a–d were used as starting materials to prepare
new functionalized pyrazole N- and N,O-bis-b-D-glucosides. Thus,

1656
N. S. A. M. Khalil / Carbohydrate Research 344 (2009) 1654–1659
glucosidation of compounds 3a–d with equimolar amount of
2,3,4,6-tetra-O-acetyl- -glucopyranosyl bromide (4) afforded a
chromatographically separable mixture (65–79% overall yield) of
two products, namely, 2-(2,3,4,6-tetra-O-acetyl-b- -glucopyrano-
syl)-4-arylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-3-one
s (5a–d) (59–72%) and 1-(2,3,4,6-tetra-O-acetyl-b- -glucopyrano-
syl)-3-(2,3,4,6-tetra-O-acetyl-b- -glucopyranosyloxy)-4-arylhydra
zono-5-trifluoromethyl-1H-pyrazoles (6a–d) (6–7%). Increasing
the molar ratio (2:1) of compound 4, when it was reacted with
compounds 3a,b, gave the same mixture but with enhanced yield
of the bis(glucosides) 6a,b (68–71%) and lower yield of the mono
glucosides 5a,b (5–8%).
3. Experimental
3.1. Synthesis
a-D
D
3.1.1. General
D
All melting points are uncorrected. IR spectra were recorded on
a Perkin-Elmer 1430 spectrometer. NMR spectra were measured
with a Varian Mercury 300 spectrometer (300 MHz 1H NMR,
75 MHz 13C NMR). Mass spectra were recorded on a GCMS-QP
1000 EX (70 EV) spectrometer. Elemental analyses were carried
out at the Micro Analytical Center, Cairo University, Giza, Egypt.
The starting 5-trifluoromethyl-2,4-dihydropyrazol-3-one (1)48
D
and 2,3,4,6-tetra-O-acetyl-a-D
-glucopyranosyl bromide (4)49 were
The structures assigned for compounds 5a–d and 6a–d were
based on spectroscopic and chemical data. Thus, the N-b-D-config-
prepared as reported. TLC was performed on Fluka silica gel 60
F254 aluminum sheets, and products were detected using 254 nm
light. Fluka silica gel 60 (70–230 mesh) was used for column
chromatography.
uration of compounds 5a–d is supported by their 1H NMR data
which revealed the anomeric proton signal at d 5.73–5.80 with a
coupling constant value 6.1–6.6 Hz consistent with reported data
for N-b-D
-glycosides.31,35,36,40,42,44 The b-configuration was con-
0
0
firmed from the large coupling constant (JH-1 -H-2 > 5 Hz) for a diax-
ial interaction.45,46 The appearance of an amide carbonyl function
at 1651–1678 cmꢀ1 in the IR spectra of compounds 5a,b is further
support of the proposed structures for compounds 5a–d. For com-
pounds 6a–d, the 1H NMR spectra revealed signals due to acetyl
protons (24 H) which appear as overlapped singlets in the region
1.80–2.12, indicating the presence of two glucosyl moieties. Also,
1H NMR spectra of these compounds revealed two characteristic
3.1.1.1. General procedure for the synthesis of 4-arylhydrazon-
o-5-trifluoromethyl-2,4-dihydropyrazol-3-ones (3a–d). To
a
cold solution of 5-trifluoromethyl-2,4-dihydropyrazol-3-one (1)
(1.52 g, 10 mmol) in EtOH (50 mL) containing NaOAc (1.64 g,
20 mmol), an aqueous solution of the appropriate aryldiazonium
salt 2a–d (10 mmol/4 mL H2O) was added dropwise with stirring
at 0–5 °C. The reaction mixture was stirred at room temperature
for 3 h and the formed precipitate was collected by filtration,
washed several times with cold water, dried, and recrystallized
from EtOH.
0
0
signals at d 5.07–5.18 (d, 1H, JH-1 -H-2 = 9.2–9.3 Hz) and 5.51–5.59
0
0
(d, 1H, JH-1 -H-2 = 9.0–9.3 Hz), which can be assigned to two ano-
meric protons of O- and N-types, respectively. The large coupling
3.1.1.1.1. 4-Phenylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-
3-one (3a). Yield 2.29 g (89%); orange yellow crystals, mp 182–
184 °C. IR: 3271, 3063, 1670, 1597, 1554, 1527, 1493, 1462,
1431, 1373, 1265, 1192, 1142, 1061, 976, 876, 764, 721, 667,
640, 594, 478; 1H NMR (CDCl3) d 7.30 (tt, 1H, J = 1.5, 7.5 Hz, ArH),
7.46 (tt, 2H, J = 1.5, 7.5 Hz, ArH), 7.51 (m, 2H, ArH), 9.84 (s, 1H,
D2O exchangeable NH), 13.70 (br, 1H, D2O exchangeable NH); 1H
NMR (DMSO-d6) d 5.17 (br, 1H, D2O exchangeable NH), 7.28 (tt,
1H, J = 1.6, 7.9 Hz, ArH), 7.47 (tt, 2H, J = 1.6, 7.9 Hz, ArH), 7.60
(dd, 2H, J = 1.6, 7.9 Hz, ArH), 12.58 (s, 1H, D2O exchangeable OH).
Anal. Calcd for C10H7F3N4O (256.1): C, 46.88; H, 2.75; N, 21.87.
Found: C, 46.75; H, 2.66; N, 22.00.
3.1.1.1.2. 4-(4-Methylphenylhydrazono)-5-trifluoromethyl-2,4-di-
hydropyrazol-3-one (3b). Yield 2.51 g (93%); orange yellow crys-
tals, mp 187 °C. IR: 3279, 3043, 2933, 2862, 2739, 1670, 1597,
1551, 1524, 1493, 1443, 1416, 1373, 1300, 1269, 1211, 1188,
1138, 1061, 976, 879, 818, 779, 760, 714, 663, 509, 482, 420; 1H
NMR (CDCl3) d 2.39 (s, 3H, CH3), 7.25 (d, 2H, J = 8.7 Hz, ArH), 7.40
(d, 2H, J = 8.5 Hz, ArH), 9.96 (s, 1H, D2O exchangeable NH), 13.76
(br, 1H, D2O exchangeable NH); 1H NMR (DMSO-d6) d 2.32 (s, 3H,
CH3), 5.17 (br, 1H, D2O exchangeable NH), 7.27 (d, 2H, J = 8.5 Hz,
ArH), 7.48 (d, 2H, J = 8.5 Hz, ArH), 12.55 (s, 1H, D2O exchangeable
OH). Anal. Calcd for C11H9F3N4O (270.1): C, 48.89; H, 3.36; N,
20.73. Found: C, 48.67; H, 3.44; N, 20.85.
0
0
constant (JH-1 -H-2 > 5 Hz) of these anomeric protons confirms a
diaxial interaction45,46 and thus supports their b-configuration.
The positions and coupling constants of these anomeric protons
0
0
0
0
at d 5.07–5.18 (JH-1 -H-2 = 9.2–9.3 Hz) and 5.51–5.59 (JH-1 -H-2
9.0–9.3 Hz) are consistent with those reported for O-b- -gluco-
sides47 and N-b- -glucosides,31,35,36,40,42,44 respectively. Moreover,
the IR spectrum of compound 6b, as a typical example, revealed
the absence of amide carbonyl function at 1651–1678 and thus
gave a further confirmation of the proposed structures for com-
pounds 6a–d. Furthermore, the appearance of the azo group
(N@N) at 1435 cmꢀ1 in compound 6b, as a typical example, to-
gether with the steric hinderance considerations, exclude any
other possible isomeric bis(glucosides).
=
D
D
Deacetylation of compounds 5a and 6a using sodium methox-
ide in methanol gave the corresponding 2-b-
phenylhydrazono-5-trifluoromethyl-2,4-dihydropyrazol-3-one (7)
D-glucopyranosyl-4-
and 1-b-D-glucopyranosyl-3-b-D-glucopyranosyloxy-4-phenylhyd-
razono-5-trifluoromethyl-1H-pyrazole (8). The 1H NMR data of
these compounds revealed the absence of the acetyl protons at d
1.80–2.12 and the appearance of the D2O exchangeable OH protons
at d 4.55–5.52.
2.2. Antimicrobial activity
3.1.1.1.3. 4-(4-Methoxyphenylhydrazono)-5-trifluoromethyl-2,4-
dihydropyrazol-3-one (3c). Yield 2.28 g (80%); reddish brown
crystals, mp 192–194 °C. IR: 3259, 3019, 2938, 2816, 2756, 1662,
1601, 1551, 1527, 1493, 1446, 1419, 1373, 1308, 1250, 1180,
1142, 1065, 1026, 976, 876, 833, 779, 752, 710, 667, 521, 478,
428; 1H NMR (CDCl3) d 3.88 (s, 3H, OCH3), 6.98 (dd, 2H, J = 2.2,
6.9 Hz, ArH), 7.46 (dd, 2H, J = 2.2, 6.9 Hz, ArH), 9.31 (s, 1H, D2O
exchangeable NH), 13.94 (br, 1H, D2O exchangeable NH). Anal.
Calcd for C11H9F3N4O2 (286.1): C, 46.16; H, 3.17; N, 19.58. Found:
C, 46.01; H, 3.21; N, 19.35.
Compounds 1, 3a–d, 5a,b, and 6a were evaluated for their anti-
bacterial and antifungal activities against two Gram-positive bac-
teria (Bacillus subtilis RCMB 101-001 and Staphylococcus aureus
RCMB 106-001 (1)), two Gram-negative bacteria (Pseudomonas
aeruginosa RCMB 102-002 and Escherichia coli RCMB 103-001),
one yeast (Candida albicans RCMB 005003), and three fungal strains
(Aspergillus fumigatus RCMB 002008 (1), Penicillium italicum RCMB
001018 (1) and Syncephalastrum racemosum RCMB 016001). The
screening results (Table 1) indicated that all the tested compounds
exhibited different inhibitory effects against five to seven different
organisms of eight test organisms. As representative examples, the
minimum inhibitory concentrations (MICs) of compounds 3a and
3.1.1.1.4. 4-(4-Chlorophenylhydrazono)-5-trifluoromethyl-2,4-
dihydropyrazol-3-one (3d). Yield 2.72 g (94%); yellow crystals, mp
220–2 °C. IR: 3171, 3101, 3028, 1666, 1593, 1554, 1531, 1485,
5a were determined and found to be 400 lg/mL.

N. S. A. M. Khalil / Carbohydrate Research 344 (2009) 1654–1659
1657
Table 1
Antimicrobial activity of compounds 1, 3a–d, 5a,b, and 6a compared to standard antimicrobial agents
Test organisms
Compound
Concentration (mg/mL)
1
2.5
5
1
2.5
5
1
2.5
3ba
5
1a
3aa
3da
6aa
Aspergillus fumigatus
Penicillium italicum
Syncephalastrum racemosum
Candida albicans
Staphylococcus aureus
Pseudomonas aeruginosa
Bacillus subtilis
0
+
0
0
0
0
0
+
0
+
0
0
0
0
0
+
+
+
+
0
0
0
+
+
++
0
0
+
0
++
+
+
++
+
0
+
0
++
+
+ (400)c
++ (400)c
+ (400)c
0
+
+
+
0
+
0
+
+
+
+
+
0
+
0
+
+
+
+
+
0
+
0
+
+
++ (400)c
0
++ (400)c
+ (400)c
Escherichia coli
++
3ca
5aa
Aspergillus fumigatus
Penicillium italicum
Syncephalastrum racemosum
Candida albicans
Staphylococcus aureus
Pseudomonas aeruginosa
Bacillus subtilis
0
+
0
0
0
0
++
+
0
+
0
0
+
0
++
+
+
+
0
+
+
0
+
0
+
+
0
+
+
0
++
0
+
+
++
+
0
++
0
0
+
0
0
++
0
0
0
+
0
0
++
0
+
+ (400)c
+ (400)c
+ (400)c
+ (400)c
++ (400)c
0
0
0
+
0
++
+
++
+
+ (400)c
+ (400)c
Escherichia coli
+
0
+
5ba
St.a,b
Aspergillus fumigatus
Penicillium italicum
Syncephalastrum racemosum
Candida albicans
Staphylococcus aureus
Pseudomonas aeruginosa
Bacillus subtilis
0
+
0
0
+
0
0
+
+
+
0
0
+
0
0
+
+
+
+
0
+
0
+
+
0
+
0
0
0
0
0
+
+
+
0
0
0
0
0
+
+
+
+
+
+
0
0
+
++
++
+++
++
++
++
++
++
+++
+++
+++
+++
++
+++
+++
++
++
++
+++
+++
++
+++
+++
++
Escherichia coli
Note: The test was done using the diffusion agar technique. Inhibition values = 0.1–0.5 cm beyond control = +; inhibition values = 0.6–1.0 cm beyond control = ++; inhibition
values = 1.0–1.5 cm beyond control = +++; 0 = not detected.
a
100
l
L of each concentration was tested (5, 2.5, 1.0 mg/mL); well diameter = 0.6 cm.
St. = reference standard; chloramphenicol was used as a standard antibacterial agent and terbinafin was used as a standard antifungal agent.
MIC values are given in brackets; MIC ( g/mL) = minimum inhibitory concentration, that is, lowest concentration to completely inhibit microbial growth.
b
c
l
1443, 1377, 1296, 1254, 1211, 1173, 1142, 1088, 1053, 1011, 976,
876, 833, 771, 725, 667, 644, 509, 471, 420; 1H NMR (CDCl3) d 7.43
(s, 4H, ArH), 9.10 (s, 1H, D2O exchangeable NH), 13.70 (br, 1H, D2O
exchangeable NH). Anal. Calcd for C10H6ClF3N4O (290.0): C, 41.33;
H, 2.08; N, 19.28. Found: C, 41.27; H, 1.97; N, 19.33.
763 mg (62%, A), 98 mg (8%, B); yellow crystals, mp 130–2 °C
(Rf = 0.21). IR: 3271, 3105, 3067, 2959, 2773, 1755, 1678, 1558,
1500, 1462, 1439, 1377, 1288, 1223, 1146, 1072, 1038, 976, 906,
806, 768, 729, 690, 598, 571, 536, 501, 459, 417; 1H NMR (CDCl3)
d
1.88, 1.90, 1.95, 1.96 (4s, 12H, CH3CO), 3.80 (ddd, 1H,
JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.9 Hz, H-50), 4.04
0
0
0
00
0
0
(dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60), 4.19 (dd, 1H,
0
0
0
00
3.1.1.2. General procedure for the synthesis of compounds 5a–d
JH-6 -H-5 = 4.8 Hz, JH-6 -H-6 = 12.6 Hz, H-600), 5.12 (dt, 1H,
00
0
00
0
and 6a–d.
(2.1 mmol) in DMF (2.5 mL) and TEA (0.36 mL, 2.6 mmol) was
added 2,3,4,6-tetra-O-acetyl- -glucopyranosyl bromide (4)
(A) To a solution of each of compounds 3a–d
JH-4 -H-2 = 2.1 Hz, JH-4 -H-3 = 6.6 Hz, JH-4 -H-5 = 9.9 Hz, H-40), 5.25
0
0
0
0
0
0
(dt, 1H, JH-3 -H-1 = 2.1 Hz, JH-3 -H-4 = 6.6 Hz, H-30), 5.28 (dt, 1H,
0
0
0
0
a-
D
JH-2 -H-4 = 2.1 Hz, JH-2 -H-1 = 6.6 Hz, H-20), 5.73 (dd, 1H, JH-1 -H-3
=
0
0
0
0
0
0
(1.03 g, 2.5 mmol) and the reaction mixture was stirred overnight.
The next day, the reaction mixture was diluted with ice-water mix-
ture and the formed precipitate was collected by filtration, washed
several times with water, and dried at room temperature. The pre-
cipitate was extracted with DCM, the solution was concentrated,
and the residue was subjected to silica gel (70–230 mesh) column
chromatography. Compounds 5a–d were eluted first with 30–40%
EtOAc/petroleum ether (bp 40–60 °C), followed by compounds 6a–
d with 40–70% EtOAc/petroleum ether (bp 40–60 °C). The chro-
matographically separated crude products were recrystallized
from DCM/petroleum ether (bp 40–60 °C). Rf values of the latter
compounds were determined on TLC aluminum sheets using
EtOAc/petroleum ether (bp 40–60 °C) [60:40, v/v] as a developing
system.
2.1 Hz, JH-1 -H-2 = 6.6 Hz, H-10), 7.38 (m, 3H, ArH), 7.74 (dd, 2H,
J = 1.6, 6.7 Hz, ArH), 13.70 (br, 1H, D2O exchangeable NH). Anal.
Calcd for C24H25F3N4O10 (586.1): C, 49.15; H, 4.30; N, 9.55. Found:
C, 48.97; H, 4.27; N, 9.39.
0
0
3.1.1.2.2. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-4-(4-methyl-
phenylhydrazono)-5-trifluoromethyl-2,4-dihydropyrazol-3-one
(5b). Yield 744 mg (59%, A), 63 mg (5%, B); yellow crystals, mp
147–149 °C. (Rf = 0.16). IR: 3236, 3031, 3006, 2959, 2757, 1755,
1651, 1621, 1616, 1558, 1500, 1439, 1373, 1230, 1142, 1038,
980, 906, 825, 756, 710, 602, 555, 478; 1H NMR (CDCl3) d 1.989,
1.997, 2.048, 2.050 (4s, 12H, CH3CO), 2.42 (s, 3H, CH3), 3.89 (ddd,
1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50),
0
0
0
00
0
0
4.14 (dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60), 4.28 (dd,
0
0
0
00
1H, JH-6 -H-5 = 4.8 Hz, JH-6 -H-6 = 12.6 Hz, H-600), 5.21 (dt, 1H,
00
0
00
0
(B) The same previous method using compound 3a,b
(2.1 mmol), DMF (5 mL), TEA (0.72 mL, 5.2 mmol), and 2,3,4,6-tetra-
JH-4 -H-2 = 2.1 Hz, JH-4 -H-3 = 9.3 Hz, JH-4 -H-5 = 9.6 Hz, H-40), 5.35
0
0
0
0
0
0
(dt, 1H, JH-3 -H-1 = 2.1 Hz, JH-3 -H-4 = 9.3 Hz, H-30), 5.36 (dt, 1H,
0
0
0
0
O-acetyl-
3.1.1.2.1. 2-(2,3,4,6-Tetra-O-acetyl-b-
hydra zono-5-trifluoromethyl-2,4-dihydropyrazol-3-one (5a). Yield
a-
D-glucopyranosyl bromide (4) (1.73 g, 4.2 mmol).
JH-2 -H-4 = 2.1 Hz, JH-2 -H-1 = JH-2 -H3 = 6.1 Hz, H-20), 5.80 (dd, 1H,
0
0
0
0
0
0
D
-glucopyranosyl)-4-phenyl-
JH-1 -H-3 = 2.1 Hz, JH-1 -H-2 = 6.1 Hz, H-10), 7.29 (d, 2H, J = 8.2 Hz,
0
0
0
0

1658
N. S. A. M. Khalil / Carbohydrate Research 344 (2009) 1654–1659
ArH), 7.74 (d, 2H, J = 8.2 Hz, ArH), 13.77 (br, 1H, D2O exchangeable
NH). Anal. Calcd for C25H27F3N4O10 (600.2): C, 50.00; H, 4.53; N,
9.33. Found: C, 49.94; H, 4.61; N, 9.24.
(2dt, 2H, J = 2.1, 9.2 Hz), 5.39 (t, 1H, J = 7.5 Hz), 5.44 (t, 1H,
J = 7.3 Hz), 5.59 (d, 1H, JH-1 -H-2 = 9.3 Hz, H-10 of N-gluc.), 6.00 (t,
1H, J = 9.3 Hz), 7.28 (d, 2H, J = 7.9 Hz, ArH), 7.79 (d, 2H, J = 7.9 Hz,
ArH). Anal. Calcd for C39H45F3N4O19 (930.3): C, 50.32; H, 4.87; N,
6.02. Found: C, 50.27; H, 4.94; N, 5.97.
0
0
3.1.1.2.3. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-4-(4-
methoxyphenylhydrazono)-5-trifluoromethyl-2,4-dihydropyrazol-3-one
(5c). Yield 815 mg (63%, A); yellow crystals, mp 146–148 °C.
(Rf = 0.18). 1H NMR (CDCl3) d 1.99 (s, 3H, CH3CO), 2.01 (s, 3H,
CH3CO), 2.05 (s, 6H, CH3CO), 3.88 (s, 3H, OCH3), 3.87 (ddd, 1H,
3.1.1.2.7. 1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-3-(2,3,4,6-tetra-
O-acetyl-b- -glucopyranosyloxy)-4-(4-methoxyphenylhydrazono)-5-tri-
D
fluoromethyl-1H-pyrazole (6c). Yield 119 mg (6%, A); yellow
crystals, mp 137 °C. (Rf = 0.07). 1H NMR (CDCl3) d 1.80–2.03 (over-
JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50), 4.15
0
0
0
00
0
0
(dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60), 4.28 (dd, 1H,
lapped singlets, 24H, CH3CO), 3.89 (ddd, 1H, JH-5 -H-6 = 2.1 Hz,
0
0
0
00
0
0
JH-6 -H-5 = 4.8 Hz, JH-6 -H-6 = 12.6 Hz, H-600), 5.20 (dt, 1H, JH-4 -H-2
=
JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50 of either N- or O-gluc.),
00
0
00
0
0
0
0
00
0
0
2.1 Hz, JH-4 -H-3 = 9.3 Hz, JH-4 -H-5 = 9.6 Hz, H-40), 5.33 (dt, 1H,
3.91 (s, 3H, OCH3), 3.94 (ddd, 1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 =
0
0
0
0
0
0
0
00
JH-3 -H-1 = 2.1 Hz, JH-3 -H-4 = 9.3 Hz, H-30), 5.36 (dt, 1H, JH-2 -H-4
=
=
4.8 Hz, JH-5 -H-4 = 9.5 Hz, H-50 of either N- or O-gluc.), 4.07 (dd,
0
0
0
0
0
0
0
0
2.1 Hz, JH-2 -H-1 = JH-2 -H3 = 6.1 Hz, H-20), 5.74 (dd, 1H, JH-1 -H-3
1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of either N- or O-
0
0
0
0
0
0
0
0
0
00
2.1 Hz, JH-1 -H-2 = 6.1 Hz, H-10), 6.99 (d, 2H, J = 9.0 Hz, ArH), 7.84
(d, 2H, J = 9.0 Hz, ArH), 13.92 (br, 1H, D2O exchangeable NH). Anal.
Calcd for C25H27F3N4O11 (616.2): C, 48.71; H, 4.41; N, 9.09. Found:
C, 48.59; H, 4.37; N, 9.03.
gluc.), 4.157 (dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of
0
0
0
0
0
00
00
0
either N- or O-gluc.), 4.163 (dd, 1H, JH-6 -H-5 = 4.2 Hz,
JH-6 -H-6 = 12.6 Hz, H-600 either N- or O-gluc.), 4.29 (dd, 1H,
00
0
JH-6 -H-5 = 4.8 Hz, JH-6 -H-6 = 12.6 Hz, H-600 of either N- or O-gluc.),
00
0
00
0
5.17 (d, 1H, JH-1 -H-2 = 9.2 Hz, H-10 of O-gluc.), 5.26 (t, 1H,
J = 9.0 Hz), 5.36 (2dt, 2H, J = 2.1, 9.2 Hz), 5.40 (t, 1H, J = 7.4 Hz),
0
0
3.1.1.2.4. 2-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-4-(4-chlo-
rophenylhydrazono)-5-trifluoromethyl-2,4-dihydropyrazol-3-one
(5d). Yield 938 mg (72%, A); yellow crystals, mp 160–2 °C.
(Rf = 0.19). 1H NMR (CDCl3) d 1.987, 2.018, 2.045, 2.048 (4s, 12H,
5.43 (t, 1H, J = 7.3 Hz), 5.58 (d, 1H, JH-1 -H-2 = 9.3 Hz, H-10 of N-
gluc.), 6.01 (t, 1H, J = 9.3 Hz), 7.00 (d, 2H, J = 9.0 Hz, ArH), 7.83 (d,
2H, J = 9.0 Hz, ArH). Anal. Calcd for C39H45F3N4O20 (946.3): C,
49.47; H, 4.79; N, 5.92. Found: C, 49.44; H, 4.65; N, 5.81.
0
0
0
0
0
00
0
0
CH3CO), 3.88 (ddd, 1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4
=
9.6 Hz, H-50), 4.17 (dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-
0
0
0
00
60), 4.27 (dd, 1H, JH-6 -H-5 = 4.8 Hz, JH-6 -H-6 = 12.6 Hz, H-600), 5.20
3.1.1.2.8. 1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-3-(2,3,4,6-tetra-
00
0
00
0
(dt, 1H, JH-4 -H-2 = 2.1 Hz, JH-4 -H-3 = 9.3 Hz, JH-4 -H-5 = 9.6 Hz, H-40),
O-acetyl-b- -glucopyranosyloxy)-4-(4-chlorophenylhydrazono)-5-tri-
D
0
0
0
0
0
0
5.33 (dt, 1H, JH-3 -H-1 = 2.1 Hz, JH-3 -H-4 = 9.3 Hz, H-30), 5.35 (dt,
fluoromethyl-1H-pyrazole (6d). Yield 140 mg (7%, A); yellow
crystals, mp 129–131 °C. (Rf = 0.07). 1H NMR (CDCl3) d 1.82–2.02
0
0
0
0
1H, JH-2 -H-4 = 2.1 Hz, JH-2 -H-1 = JH-2 -H3 = 6.1 Hz, H-20), 5.70 (dd,
0
0
0
0
0
0
1H, JH-1 -H-3 = 2.1 Hz, JH-1 -H-2 = 6.1 Hz, H-10),
d
7.47 (d, 2H,
(overlapped singlets, 24H, CH3CO), 3.89 (ddd, 1H, JH-5 -H-6 =
0
0
0
0
0
0
2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50 of either N- or O-
0
00
0
0
J = 9.0 Hz, ArH), 7.79 (d, 2H, J = 9.0 Hz, ArH), 13.71 (br, 1H, D2O
exchangeable NH). Anal. Calcd for C24H24ClF3N4O10 (620.1): C,
46.42; H, 3.90; N, 9.02. Found: C, 46.55; H, 3.96; N, 8.87.
0
0
0
00
0
0
gluc.), 3.96 (ddd, 1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4
=
=
9.6 Hz, H-50 of either N- or O-gluc.), 4.07 (dd, 1H, JH-6 -H-5
0
0
2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of either N- or O-gluc.), 4.153 (dd,
0
00
3.1.1.2.5. 1-(2,3,4,6-Tetra-O-acetyl-b-D-glucopyranosyl)-3-(2,3,4,6-tetra-
1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of either N- or O-
0
0
0
00
O-acetyl-b- -glucopyranosyloxy)-4-phenylhydrazono-5-trifluoro-
D
gluc.), 4.159 (dd, 1H, JH-6 -H-5 = 4.2 Hz, JH-6 -H-6 = 12.6 Hz, H-600
00
0
00
0
methyl-1H-pyrazole (6a). Yield: 115 mg (6%, A), 1.31 (68%, B) mp
121–123 °C (Rf = 0.07). 1H NMR (CDCl3) d 1.9–2.12 (overlapped
00
0
00
0
either N- or O-gluc.), 4.32 (dd, 1H, JH-6 -H-5 = 4.8 Hz, JH-6 -H-6
=
=
singlets, 24H, CH3CO), 3.89 (ddd, 1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6
=
12.6 Hz, H-600 of either N- or O-gluc.), 5.18 (d, 1H, JH-1 -H-2
0
0
0
00
0
0
4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50 of either N- or O-gluc.), 3.95 (ddd,
9.3 Hz, H-10 of O-gluc.), 5.27 (t, 1H, J = 8.8 Hz), 5.35 (2dt, 2H,
J = 2.1, 9.3 Hz), 5.42 (t, 1H, J = 7.5 Hz), 5.44 (t, 1H, J = 7.4 Hz), 5.58
0
0
1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50 of
0
0
0
00
0
0
0
0
0
00
0
0
either N- or O-gluc.), 4.16 (dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6
=
=
(d, 1H, JH-1 -H-2 = 9.3 Hz, H-10 of N-gluc.), 6.05 (t, 1H, J = 9.3 Hz),
7.47 (d, 2H, J = 9.0 Hz, ArH), 7.80 (d, 2H, J = 9.0 Hz, ArH) Anal. Calcd
for C38H42ClF3N4O19 (950.2): C, 47.98; H, 4.45; N, 5.89. Found: C,
48.04; H, 4.33; N, 5.77.
12.6 Hz, H-60 of either N- or O-gluc.), 4.256 (dd, 1H, JH-6 -H-5
0
0
2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of either N- or O-gluc.), 4.265 (dd,
0
00
1H, JH-6 -H-5 = 4.2 Hz, JH-6 -H-6 = 12.6 Hz, H-600 either N- or O-gluc.),
00
0
00
0
4.38 (dd, 1H, JH-6 -H-5 = 4.8 Hz, JH-6 -H-6 = 12.6 Hz, H-600 of either N-
00
0
00
0
or O-gluc.), 5.07 (d, 1H, JH-1 -H-2 = 9.3 Hz, H-10 of O-gluc.), 5.17 (t,
1H, J = 7.8 Hz), 5.28 (2dt, 2H, J = 2.1, 9.6 Hz), 5.30 (t, 1H,
3.1.1.3. General procedure for deacetylation of compounds 5a
0
0
and 6a.
To a stirred solution of compounds 5a and 6a
0
0
J = 7.5 Hz), 5.36 (t, 1H, J = 7.3 Hz), 5.51 (d, 1H, JH-1 -H-2 = 9.0 Hz, H-
10 of N-gluc.), 5.92 (t, 1H, J = 9.0 Hz), 7.38 (m, 3H, ArH), 7.78 (dd,
2H, J = 1.8, 8.1 Hz, ArH). Anal. Calcd for C38H43F3N4O19 (916.2): C,
49.78; H, 4.73; N, 6.11. Found: C, 49.76; H, 4.58; N, 5.99.
(1 mmol) in anhydrous MeOH (10 mL) was added portion wise
NaOMe [0.054 g (1 mmol) and 0.108 g (2 mmol), for compounds
5a and 6a, respectively] in anhydrous MeOH (10 mL) at room tem-
perature and the solution was stirred overnight. After evaporation
of solvent in vacuo, H2O (15 mL) was added and the mixture was
extracted several times with DCM to remove the ester formed dur-
ing the deprotection. To the resulting aqueous solution was added
an ion exchange resin (Dowex 50W ꢁ 2, H+ form), previously
washed with MeOH. After stirring for five minutes, the solution
was filtered, evaporated in vacuo and the residue chromato-
graphed on silica gel with the gradient 0–10% MeOH in HCCl3 to
give compounds 7 and 8. Rf values of the latter compounds were
determined using TLC aluminum sheets and HCCl3/MeOH (60:40,
v/v) as a developing system.
3.1.1.2.6. 1-(2,3,4,6-Tetra-O-acetyl-b-
D-glucopyranosyl)-3-(2,3,4,6-
tetra-O-acetyl-b- -glucopyranosyloxy)-4-(4-methylphenylhydrazono)-
D
5-trifluoromethyl-1H-pyrazole (6b). Yield 117 mg (6%, A), 1.39 g
(71%, A); yellow crystals, mp 131–3 °C. (Rf = 0.06). IR: 2959, 2739,
1755, 1639, 1620, 1504, 1435, 1373, 1227, 1142, 1073, 1038,
984, 906, 829, 748, 602, 474. 1H NMR (CDCl3) d 1.81–2.02 (over-
lapped singlets, 24H, CH3CO), 2.42 (s, 3H, CH3), 3.89 (ddd, 1H,
JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz, JH-5 -H-4 = 9.6 Hz, H-50 of either
0
0
0
00
0
0
0
0
0
00
N- or O-gluc.), 3.95 (ddd, 1H, JH-5 -H-6 = 2.1 Hz, JH-5 -H-6 = 4.8 Hz,
JH-5 -H-4 = 9.6 Hz, H-50 of either N- or O-gluc.), 4.08 (dd, 1H,
0
0
JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of either N- or O-gluc.),
3.1.1.3.1. 2-b-D-Glucopyranosyl-4-phenylhydrazono-5-trifluoro-
0
0
0
00
4.156 (dd, 1H, JH-6 -H-5 = 2.1 Hz, JH-6 -H-6 = 12.6 Hz, H-60 of either
methyl-2,4-dihydropyrazol-3-one (7). Yield 376 mg (90%); yellow
crystals, mp 210–212 °C (Rf = 0.29). MS: m/z = 418 (M+). 1H NMR
(DMSO-d6) d 3.11–3.39 (m, 4H, H-20, H-30, H-40, H-50), 3.45 (dd,
0
0
0
00
00
0
00
0
N- or O-gluc.), 4.162 (dd, 1H, JH-6 -H-5 = 4.2 Hz, JH-6 -H-6 = 12.6 Hz,
H-600 either N- or O-gluc.), 4.30 (dd, 1H, JH-6 -H-5 = 4.8 Hz,
00
0
JH-6 -H-6 = 12.6 Hz, H-600 of either N- or O-gluc.), 5.16 (d, 1H,
1H, JH-6 -OH = 5.7 Hz, JH-6 -H-6 = 11.7 Hz,), 3.64 (dd, 1H,
00
0
0
0
00
JH-1 -H-2 = 9.3 Hz, H-10 of O-gluc.), 5.26 (t, 1H, J = 8.8 Hz), 5.35
JH-6 -H-5 = 2.3 Hz, JH-6 -H-6 = 11.7 Hz, H-600), 4.55 (br, 1H, D2O-
0
0
00
0
00
0

N. S. A. M. Khalil / Carbohydrate Research 344 (2009) 1654–1659
1659
4. Gregory, T. P.; Darlene, C. D.; David, M. S. Pestic. Biochem. Phys. 1998, 60, 177.
5. Kucukguzel, S. G.; Rollas, S.; Erdeniz, H.; Kiraz, A. C.; Ekinci, M.; Vidin, A. Eur. J.
Med. Chem. 2000, 35, 761.
6. Mutalib, A. E.; Chen, S. Y.; Espina, R. J.; Shockcor, J.; Prakash, S. R.; Gan, L.-S.
Chem. Res. Toxicol. 2002, 15, 63.
7. Jadeja, R. N.; Shah, J. R.; Suresh, E.; Paul, P. Polyhedron 2004, 23, 2465–2474. and
references cited therein.
8. Gürsoy, A.; Demirayak, M. S.; Çapan, G.; Erol, K.; Vural, K. Eur. J. Med. Chem.
2000, 35, 359.
exchangeable OH), 5.00 (d, 1H, J = 5.4 Hz, D2O-exchangeable OH),
5.14 (d, 1H, J = 4.8 Hz, D2O-exchangeable OH), 5.52 (br, 1H, D2O-
exchangeable OH), 5.56 (d, 1H, JH-1 -H-2 = 9.3 Hz, H-10), 7.47 (m,
3H, ArH), 7.82 (dd, 2H, J = 1.5, 7.0 Hz, ArH), 13.53 (br, 1H, D2O-
exchangeable NH). Anal. Calcd for C16H17F3N4O6 (418.1): C,
45.94; H, 4.10; N, 13.39. Found: C, 45.88; H, 4.09; N, 13.22.
0
0
3.1.1.3.2. 1-b-D-Glucopyranosyl-3-b-D-glucopyranosyloxy-4-phenyl-
9. Badawey, E. A. M.; El-Ashmawey, I. M. Eur. J. Med. Chem. 1998, 33, 349.
10. (a) Jiang, J. B.; Hesson, D. P.; Dusak, B. A.; Dexter, D. L.; Kang, G. J.; Hamel, E. J.
Med. Chem. 1990, 33, 1721; (b) Anzai, K.; Furuse, M.; Yoshida, A.; Matsuyama,
A.; Moritake, T.; Tsuboi, K.; Ikota, N. J. Radiat. Res. 2004, 45, 319.
11. Qi, X.; Okuma, Y.; Hosoi, T.; Nombra, Y. J. Pharmacol. Exp. Ther. 2004, 311, 388.
12. Abe, S.; Kirima, K.; Tsuchiya, K.; Okamoto, M.; Hasegawa, T.; Houchi, H.;
Yoshizumi, M.; Tamaki, T. Chem. Pharm. Bull. 2004, 52, 186.
13. Tong, A.; Akama, Y.; Tanaka, S. J. Chromatography 1989, 478, 408.
14. Akama, Y.; Tang, A.; Ishima, S.; Kaijitani, M. Anal. Sci. 1992, 8, 41.
15. Umetani, S.; Freiser, H. Inorg. Chem. 1987, 26, 3179.
16. Zolotov, Y. A.; Kuzmin, N. M. In Metal Extraction with Acylpyrazolones; Izdat
Nauka: Moscow, 1977.
17. Okafor, E. C.; Uzoukwu, B. A. Radiochim. Acta 1990, 51, 167.
18. Samelson, H.; Lempicki, A. J. Chem. Phys. 1963, 39, 110.
19. Charles, R. G.; Riedel, E. P. J. Inorg. Nucl. Chem. 1966, 28, 3005.
20. Hinkley, C. C. J. Am. Chem. Soc. 1969, 91, 5160.
21. Horrrocks, W. D., Jr.; Sipe, J. P., III J. Am. Chem. Soc. 1971, 93, 6800.
22. Berg, E. W.; Acosta, J. J. C. Anal. Chim. Acta 1968, 40, 101.
23. Liu, L.; Jia, D. Z.; Ji, Y. L.; Yu, K. B. J. Photochem. Photobiol. 2003, 154, 117.
24. Akama, Y.; Tong, A.; Matsumoto, N.; Ikeda, T.; Tanaka, S. Vib. Spectrosc. 1996,
13, 113.
hydrazono-5-trifluoromethyl-1H-pyrazole (8). Yield 435 mg (75%);
yellow crystals, mp 202–204 °C (Rf = 0.1). MS: m/z = 580 (M+). 1H
NMR (DMSO-d6) d 3.08–3.42 (m, 8H, H-20, H-30, H-40, H-50 of both
0
0
00
N- and O-glucs.), 3.45 (dd, 1H, JH-6 -OH = 5.7 Hz, JH-6 -H-6 = 11.7 Hz,
H-60 of either N- or O-gluc.), 3.48 (dd, 1H, JH-6 -OH = 5.1 Hz,
0
JH-6 -H-6 = 12.0 Hz, H-60 of either N- or O-gluc.), 3.64 (dd,
0
00
1H, JH-6 -H-5 = 2.3 Hz, JH-6 -H-6 = 11.7 Hz, H-600 of either N- or O-
00
0
00
0
gluc.), 3.66 (dd, 1H, JH-6 -H-5 = 2.5 Hz, JH-6 -H-6 = 12.0 Hz, H-600 of
either N- or O-gluc.), 4.55 (br, 2H, D2O-exchangeable OH), 4.89
00
0
00
0
(d, 1H, JH-1 -H-2 = 8.7 Hz, H-10 of O-gluc.), 5.00 (d, 1H, J = 5.4 Hz,
D2O-exchangeable OH), 5.02 (br s, 1H, D2O-exchangeable OH),
5.11 (br s, 1H, D2O-exchangeable OH) , 5.14 (d, 1H, J = 4.8 Hz,
D2O-exchangeable OH), 5.52 (br, 2H, D2O-exchangeable OH), 5.55
0
0
(d, 1H, JH-1 -H-2 = 9.3 Hz, H-10). 7.46 (m, 3H, ArH), 7.78 (dd, 2H,
J = 1.8, 8.1 Hz, ArH). Calcd for C22H27F3N4O11 (580.16): C, 45.52;
H, 4.69; N, 9.65. Found: C, 45.71; H, 4.66; N, 9.77.
0
0
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for Mycology and Biotechnology, Faculty of Science, Al-Azhar Uni-
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2.5 and 1 mg/mL concentrations. All the compounds were tested
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