Synthesis, structural determination, and biological activity of new 7-hydroxy-3-pyrazolyl-4H-chromen- 4-ones and their o-β-D-glucosides

Article abstract of DOI:10.3906/kim-0902-11

A convenient route to synthesize some new medicinally important 7-hydroxy-3-pyrazolyl chromones (3ai) is described. The interaction of 7-hydroxy-3-formyl chromone (1) with various substituted acetophenones and further cyclization with hydrazine hydrate in an aprotic solvent followed by condensation with 2, 3, 4, 6-tetra-o-acetyl-a-d-glucopyranosyl bromide afforded 2, 3, 4, 6-tetra-o-acetyl-β -d-glucopyranosyloxy- 3-(3-aryl-1H-pyrazol-5- yl)-4H-chromen-4-ones (4a-i). Later deacetylation with anhydrous zinc acetate in methanol gave 7-o-β -d-glucopyranosyloxy-3-(3-aryl-1H -pyrazol-5-yl)-4H- chromen-4-ones (5a-i). These compounds were evaluated for their in vitro antimicrobial and anti-oxidant activity. The structures of these newly synthesized o-glucosides were established by IR, NMR, mass spectra, elemental analysis, and chemical analysis. TUeBITAK.

Full text of DOI:10.3906/kim-0902-11

Turk J Chem
34 (2010) , 241 – 254.
¨
˙
c
ꢀ TUBITAK
doi:10.3906/kim-0902-11
Synthesis, structural determination, and biological
activity of new 7-hydroxy-3-pyrazolyl-4H-chromen-
4-ones and their o-β-D-glucosides
Kishor HATZADE1,2,∗, Vijay TAILE1, Pravin GAIDHANE1 and Vishwas INGLE1
1Organic Research Lab, Department of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University,
Nagpur-440 033, INDIA
2Department of Chemistry, Dhote Bandhu Science College, Gondia-441 614, INDIA
e-mail: g kishor2000@yahoo.co.in, kishorhatzade@gmail.com
Received 06.02.2009
A convenient route to synthesize some new medicinally important 7-hydroxy-3-pyrazolyl chromones (3a-
i) is described. The interaction of 7-hydroxy-3-formyl chromone (1) with various substituted acetophenones
and further cyclization with hydrazine hydrate in an aprotic solvent followed by condensation with 2, 3,
4, 6-tetra-o-acetyl-α-d-glucopyranosyl bromide afforded 2, 3, 4, 6-tetra-o-acetyl-β -d-glucopyranosyloxy-
3-(3-aryl-1H -pyrazol-5-yl)-4H -chromen-4-ones (4a-i). Later deacetylation with anhydrous zinc acetate
in methanol gave 7-o-β -d-glucopyranosyloxy-3-(3-aryl-1H -pyrazol-5-yl)-4H -chromen-4-ones (5a-i). These
compounds were evaluated for their in vitro antimicrobial and anti-oxidant activity. The structures of these
newly synthesized o-glucosides were established by IR, NMR, mass spectra, elemental analysis, and chemical
analysis.
Key Words: Chromones, pyrazoles, glucopyranosyl bromide, glucosylation, o-β -d-glucosides.
Introduction
The flavonoids represent one of the largest groups of natural products known; several thousand derivatives have
been identified.1 In addition to the various functions of flavonoids in plants, their widespread distribution in na-
ture, their structural variability, their relatively low toxicity, and their antioxidant activities have increased the
interest in flavonoids as beneficial for human health.2 Several therapeutically interesting biological activities of
certain flavonoids have been reported including anticancer,3−8 anti-HIV,9−11 and antioxidant properties. 12−14
∗Corresponding author
241

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Similarly pyrazole is found widely as a core structure in a large variety of compounds that exhibit important
biological activity.15 It is convenient to synthesize substituted pyrazoles by the intermolecular [3+2] cycload-
dition of 1, 3-dipoles with alkynes or condensation of hydrazine with 1, 3-diketones or their equivalents.16 The
use of combinatorial approaches to the high-throughput synthesis of this drug-like scaffold would be a powerful
advance in helping to speed up drug discovery. On the other hand, carbohydrates are being considered as
extremely useful stereo chemical building blocks for complex organic synthesis.17 Apart from being an energy
source in leaving systems, carbohydrates increasingly are being recognized as important actors in a variety of
biological processes, such as signaling, cell-cell communications, and molecular and cellular targeting.18
The great importance of this category of heterocycles and continuation of our studies19 on chromone
based heterocycles oriented our attention to the synthesis of a series of new heterocyclic derivatives combining
chromones, pyrazoles, and carbohydrate moieties in one molecular frame as new possible biological active
compounds. Herein we report the synthesis of chromones bearing a pyrazole ring at position 3 and carbohydrate
moiety at position 7, starting from the corresponding 7-hydroxy-3-formyl-4H-chromen-4-one, together with the
results on their biological activities.
Experimental
Melting points were determined on a liquid paraffin bath in an open capillary tube and were uncorrected. FT-
IR spectra were recorded using KBr on a Perkin-Elmer infrared spectrophotometer; 1 H-NMR and 13 C-NMR
spectra were recorded on a Brucker II-400 NMR spectrometer, using TMS as an internal standard in DMSO-d6
as a solvent; chemical shifts (δ) are measured in ppm. Mass spectra were determined on Hitachi Perkin-Elmer
RMU 6D mass spectrometer. Elemental analysis was performed using a Perkin-Elmer 2400 CHN analyzer.
Purity of the compounds was checked on silica gel plates using iodine vapor as visualizing agent.
General procedure for 7-hydroxy-3-(3-aryl-1H-pyrazol-5-yl)-4H -chromen-4-ones (3a-i). A
mixture of 7-hydroxy-3-(3-aryl-3-oxoprop-1-enyl)-4H-chromen-4-ones (2a-i) (0.01 mol), hydrazine hydrate
(0.01 mol), and DMF (10 mL) was refluxed 18 h in an oil bath. The reaction mixture was cooled and added to
crushed ice, and the solid obtained was filtered and washed with water, dried, and recrystallized from DMF.
7-Hydroxy-3-(3-phenyl-1H-pyrazol-5-yl)-4H -chromen-4-one (3a). Yield 67%, mp 281 ˚C, IR
(KBr) cm−1 : 3367.7 (br, OH), 2931.6 (N-H), 1719.9 (C=O), 1457.1 (C=N), 1034.0 (C-O-C). (EI-MS) m/z(%):
304 (100), 161 (25), 77 (24). Anal. Calcd for C18 H12 N2 O3 : C, 71.05; H, 3.97; N, 9.21. Found: C, 71.02; H,
3.95; N, 9.20 (%).
7-Hydroxy-3-[3-(4-chloro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3b). Yield 65%, mp
312 ˚C, IR (KBr) cm−1 : 3300.4 (br, OH), 2945.1 (N-H), 1684.7 (C=O), 1451.4 (C=N), 1098.6 (C-O-C). (EI-
MS) m/z (%): 338 (100), 161 (18), 112 (21). Anal. Calcd for C18 H11 ClN2 O3 : C, 63.82; H, 3.27; N, 8.27.
Found: C, 63.80; H, 3.25; N, 8.24 (%).
7-Hydroxy-3-[3-(4-bromo phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3c). Yield 60%, mp
295 ˚C, IR (KBr) cm−1 : 3455.1 (br, OH), 2944.4 (N-H), 1714.8 (C=O), 1454.7 (C=N), 1054.6 (C-O-C). (EI-
MS) m/z (%): 382 (100), 161 (11), 157 (22). Anal. Calcd for C18 H11 BrN2 O3 : C, 56.42; H, 2.89; N, 7.31.
Found: C, 56.40; H, 2.86; N, 7.25 (%).
7-Hydroxy-3-[3-(4-methyl phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3d). Yield 67%, mp
242

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
241 ˚C, IR (KBr) cm−1 : 3411.0 (br, OH), 2934.6 (N-H), 1700.4 (C=O), 1461.1 (C=N), 1074.6 (C-O-C). (EI-
MS) m/z (%): 318 (100), 161 (23), 90 (17). Anal. Calcd for C19 H14 N2 O3 : C, 71.69; H, 4.43; N, 8.80. Found:
C, 71.65; H, 4.37; N, 8.78 (%).
7-Hydroxy-3-[3-(4-methoxy phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3e). Yield 55%, mp
265 ˚C, IR (KBr) cm−1 : 3443.4 (br, OH), 2934.6 (N-H), 1701.3 (C=O), 1458.9 (C=N), 1078.6 (C-O-C). Anal.
Calcd for C19 H14 N2 O4 : C, 68.26; H, 4.22; N, 8.38. Found: C, 68.25; H, 4.20; N, 8.35 (%).
7-Hydroxy-3-[3-(2, 4-dichloro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3f). Yield 63%,
mp 221 ˚C, IR (KBr) cm−1 : 3391.2 (br, OH), 2947.8 (N-H), 1713.5 (C=O), 1451.2 (C=N), 1055.2 (C-O-C).
(EI-MS) m/z (%): 372 (100), 161 (17), 77 (29). Anal. Calcd for C18 H10 Cl2 N2 O3 : C, 57.77; H, 2.96; N, 7.49.
Found: C, 57.75; H, 2.90; N, 7.45 (%).
7-Hydroxy-3-[3-(3, 4-dichloro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3g). Yield 61%,
mp 211 ˚C, IR (KBr) cm−1 : 3444.0 (br, OH), 2938.9 (N-H), 1719.5 (C=O), 1459.1 (C=N), 1049.6 (C-O-C).
Anal. Calcd for C18 H10 Cl2 N2 O3 : C, 57.77; H, 2.96; N, 7.49. Found: C, 57.75; H, 2.90; N, 7.45 (%).
7-Hydroxy-3-[3-(3-nitro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3h). Yield 45%, mp
260 ˚C, IR (KBr) cm−1 : 3389.4 (br, OH), 2945.8 (N-H), 1710.6 (C=O), 1451.0 (C=N), 1078.6 (C-O-C). Anal.
Calcd for C18 H11 N3 O5 : C, 61.89; H, 3.17; N, 12.03. Found: C, 61.85; H, 3.15; N, 12.01 (%).
7-Hydroxy-3-[3-(4-nitro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (3i). Yield 55%, mp 220
˚C, IR (KBr) cm−1 : 3440.3 (br, OH), 2927.8 (N-H), 1738.8 (C=O), 1451.8 (C=N), 1098.6 (C-O-C). Anal.
Calcd for C18 H11 N3 O5 : C, 61.89; H, 3.17; N, 12.03. Found: C, 61.85; H, 3.15; N, 12.01 (%).
General procedure for 2, 3, 4, 6-tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-(3-aryl-1H-
pyrazol-5-yl)-4H-chromen-4-ones (4a-i). In a 25 mL round-bottomed flask, anhydrous K2 CO3 (6.3 mmol)
was added to the mixture of DMF (9 mL) and acetone (6 mL), and then 7-hydroxy-3-[3-aryl-1H-pyrazol-5-yl]-
4H -chromen-4-ones (3a-i) (0.30 mmol), DTMAB (10 mg), and α-acetylbromoglucose (0.60 mmol) were added
under stirring, and the reaction mixture was refluxed for 5-6 h (monitored by TLC). Then acetone was removed
under vacuum and water (20 mL) was added to the flask. The mixture was extracted with ethyl acetate (5 ×
10 mL), the organic layer was washed with 20 mL of water and brine, and dried over anhydrous MgSO4 , and
then the solvent was removed to give the residue, which was purified by silica gel flash chromatography (ethyl
acetate: petroleum ether 1 : 2 v/v) to give a brown semisolid.
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-phenyl-1H-pyrazol-5-yl]-4H -chro-
men-4-one (4a). Yield 95%, [α]2D5 = -21.2 (c 0.1 in DMSO), IR (KBr) cm−1 : 3042.1 (Ar-CH), 2954.0 (N-H),
2854.3 (glucosidic-CH), 1760.8 (C=O of o-acetyl gps of glycone moiety), 1721.7 (C=O), 1454.4 (C=N), 1120.6
(C-O-C). Anal. Calcd for C32 H30 N2 O12 : C, 60.57; H, 4.77; N, 4.41. Found: C, 60.55; H, 4.74; N, 4.39 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(4-chloro phenyl)-1H-pyrazol-5-
yl]-4H -chromen-4-one (4b). Yield 90%, [α]D25 = -20.9 (c 0.1 in DMSO), IR (KBr) cm−1 : 3044.2 (Ar-CH),
2966.4 (N-H), 2857.3 (glucosidic-CH), 1754.2 (C=O of o-acetyl gps of glycone moiety), 1722.8 (C=O), 1451.5
(C=N), 1078.6 (C-O-C). Anal. Calcd for C32 H29 ClN2 O12 : C, 57.45; H, 4.37; N, 4.19. Found: C, 57.41; H,
4.40; N, 4.15 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(4-bromo phenyl)-1H-pyrazol-5-
yl]-4H -chromen-4-one (4c). Yield 81%, [α]D25 = -15.4 (c 0.1 in DMSO), IR (KBr) cm−1 : 3040.6 (Ar-CH),
2956.5 (N-H), 2852.1 (glucosidic-CH), 1765.4 (C=O of o-acetyl gps of glycone moiety), 1724.5 (C=O), 1452.1
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Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
(C=N), 1048.6 (C-O-C). Anal. Calcd for C32 H29 BrN2 O12 : C, 53.87; H, 4.10; N, 3.93. Found: C, 53.85; H,
4.09; N, 3.90 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(4-methyl phenyl)-1H-pyrazol-5-
yl]-4H -chromen-4-one (4d). Yield 91%, [α]D25 = -14.6 (c 0.1 in DMSO), IR (KBr) cm−1 : 3041.8 (Ar-CH),
2956.8 (N-H), 2856.8 (glucosidic-CH), 1761.2 (C=O of o-acetyl gps of glycone moiety), 1726.4 (C=O), 1454.7
(C=N), 1078.9 (C-O-C). Anal. Calcd for C33 H32 N2 O12 : C, 61.11; H, 4.97; N, 4.32. Found: C, 61.08; H, 4.93;
N, 4.30 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(4-methoxy phenyl)-1H-pyrazol-5-
yl]-4H -chromen-4-one (4e). Yield 78%, [α]D25 = -17.5 (c 0.1 in DMSO), IR (KBr) cm−1 : 3037.3 (Ar-CH),
2973.1 (N-H), 2861.7 (glucosidic-CH), 1754.8 (C=O of o-acetyl gps of glycone moiety), 1727.9 (C=O), 1460.7
(C=N), 1100.0 (C-O-C). Anal. Calcd for C33 H32 N2 O13 : C, 59.64; H, 4.85; N, 4.21. Found: C, 59.60; H, 4.80;
N, 4.20 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(2, 4-dichloro phenyl)-1H-pyrazol-
5-yl]-4H -chromen-4-one (4f). Yield 87%, [α]2D5 = -16.4 (c 0.1 in DMSO), IR (KBr) cm−1 : 3045.4 (Ar-CH),
2964.8 (N-H), 2851.8 (glucosidic-CH), 1761.6 (C=O of o-acetyl gps of glycone moiety), 1700.8 (C=O), 1457.8
(C=N), 1077.8 (C-O-C). Anal. Calcd for C32 H28 Cl2 N2 O12 : C, 54.63; H, 4.01; N, 3.98. Found: C, 54.60; H,
4.00; N, 3.91 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(3, 4-dichloro phenyl)-1H-pyrazol-
5-yl]-4H -chromen-4-one (4g). Yield 84%, [α]2D5 = -15.0 (c 0.1 in DMSO), IR (KBr) cm−1 : 3054.8 (Ar-CH),
2959.8 (N-H), 2857.4 (glucosidic-CH), 1766.1 (C=O of o-acetyl gps of glycone moiety), 1717.8 (C=O), 1451.4
(C=N), 1078.1 (C-O-C). Anal. Calcd for C32 H28 Cl2 N2 O12 : C, 54.63; H, 4.01; N, 3.98. Found: C, 54.60; H,
4.00; N, 3.91 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(3-nitro phenyl)-1H-pyrazol-5-yl]-
4H -chromen-4-one (4h). Yield 84%, [α]D25 = -19.6 (c 0.1 in DMSO), IR (KBr) cm−1 : 3044.7 (Ar-CH),
2955.5 (N-H), 2851.6 (glucosidic-CH), 1764.5 (C=O of o-acetyl gps of glycone moiety), 1708.9 (C=O), 1457.7
(C=N), 1048.1 (C-O-C). Anal. Calcd for C32 H29 N3 O14 : C, 56.56; H, 4.30; N, 6.18. Found: C, 56.52; H, 4.25;
N, 6.13 (%).
2, 3, 4, 6-Tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-[3-(4-nitro phenyl)-1H-pyrazol-5-yl]-
4H -chromen-4-one (4i). Yield 80%, [α]D25 = -19.4 (c 0.1 in DMSO), IR (KBr) cm−1 : 3047.4 (Ar-CH),
2954.0 (N-H), 2851.9 (glucosidic-CH), 1760.4 (C=O of o-acetyl gps of glycone moiety), 1714.7 (C=O), 1454.8
(C=N), 1088.1 (C-O-C). Anal. Calcd for C32 H29 N3 O14 : C, 56.56; H, 4.30; N, 6.18. Found: C, 56.52; H, 4.25;
N, 6.13 (%).
General procedure for 7-o-β-d-glucopyranosyloxy-3-(3-aryl-1H-pyrazol-5-yl)-4H-chromen-
4-ones (5a-i). The mixture of 2, 3, 4, 6-tetra-o-acetyl-7-o-β-d-glucopyranosyloxy-3-(3-aryl-1H-pyrazol-5-
yl)-4H -chromen-4-ones (4a-i) (0.109 mmol), dry methanol (2 mL), and anhydrous zinc acetate (0.126 mmol)
was refluxed for 7-8 h (monitored by TLC). After cooling at room temperature, it was filtered through cation
exchanged resin; the solvent was removed under vacuum. The residue was purified by silica gel chromatography
(CHCl3 , MeOH, 12:1 v/v) to get a brown semisolid.
7-o-β-d-Glucopyranosyloxy-3-[3-phenyl-1H-pyrazol-5-yl]-4H -chromen-4-one (5a). Yield 85%,
[α]2D5 = -9.7 (c 0.1 in DMSO), IR (KBr) cm−1 : 3412.4 (br, OH peak of carbohydrate residue), 2945.8 (N-H),
244

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
2857.5 (glucosidic-CH), 1717.9 (C=O), 1445.7 (C=N), 1072.1 (C-O-C), 683.1 (benzene monosubstituted). (EI-
MS) m/z (%): 467 [M+ ] (11), 304 (100), 163 (45), 161 (20), 77 (23). Anal. Calcd for C24 H22 N2 O8 : C, 61.80;
H, 4.75; N, 6.01. Found: C, 61.75; H, 4.74; N, 5.99 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(4-chloro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (5b).
Yield 79%, [α]D25 = -10.1 (c 0.1 in DMSO), IR (KBr) cm−1 : 3424.8 (br, OH peak of carbohydrate residue),
2946.7 (N-H), 2845.7 (glucosidic-CH), 1712.8 (C=O), 1455.1 (C=N), 1089.4 (C-O-C). (EI-MS) m/z (%): 501
[M+ ] (9), 338 (100), 163 (33), 161 (15), 77 (18). Anal. Calcd for C24 H21 ClN2 O8 : C, 57.56; H, 4.23; N, 5.59.
Found: C, 57.51; H, 4.20; N, 5.52 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(4-bromo phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (5c).
Yield 83%, [α]D25 = -12.1 (c 0.1 in DMSO), IR (KBr) cm−1 : 3399.1 (br, OH peak of carbohydrate residue),
2978.5 (N-H), 2844.1 (glucosidic-CH), 1729.3 (C=O), 1444.7 (C=N), 1091.8 (C-O-C). Anal. Calcd for C24 H21
BrN2 O8 : C, 52.86; H, 3.88; N, 5.14. Found: C, 52.84; H, 3.85; N, 5.11 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(4-methyl phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one
(5d). Yield 75%, [α]2D5 = -5.9 (c 0.1 in DMSO), IR (KBr) cm−1 : 3424.8 (br, OH peak of carbohydrate
residue), 2912.4 (N-H), 2858.7 (glucosidic-CH), 1727.8 (C=O), 1459.1 (C=N), 1089.8 (C-O-C). (EI-MS) m/z
(%): 481 [M+ ](14), 318 (100), 163 (25), 161 (31), 77 (13). Anal. Calcd for C25 H24 N2 O8 : C, 62.49; H, H 5.03;
N, 5.83. Found: C, 62.45; H, 5.04; N, 5.80 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(4-methoxy phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one
(5e). Yield 74%, [α]2D5 = -8.4 (c 0.1 in DMSO), IR (KBr) cm−1 : 3419.7 (br, OH peak of carbohydrate
residue), 2919.7 (N-H), 2849.7 (glucosidic-CH), 1700.2 (C=O), 1455.7 (C=N), 1092.6 (C-O-C). Anal. Calcd for
C25 H24 N2 O9 : C, 60.48; H, 4.87; N, 5.64. Found: C, 60.45; H, 4.80; N, 5.60 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(2, 4-dichloro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one
(5f). Yield 70%, [α]2D5 = -12.0 (c 0.1 in DMSO), IR (KBr) cm−1 : 3421.0 (br, OH peak of carbohydrate
residue), 2918.9 (N-H), 2851.7 (glucosidic-CH), 1701.8 (C=O), 1445.2 (C=N), 1073.3 (C-O-C). (EI-MS) m/z
(%): 535 [M+ ] (21), 372 (100), 163 (37), 161 (18), 77 (23). Anal. Calcd for C24 H20 Cl2 N2 O8 : C, 53.85; H,
3.77; N, 5.23. Found: C, 53.80; H, 3.74; N, 5.21 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(3, 4-dichloro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one
(5g). Yield 80%, [α]2D5 = -10.7 (c 0.1 in DMSO), IR (KBr) cm−1 : 3405.8 (br, OH peak of carbohydrate
residue), 2943.6 (N-H), 2857.8 (glucosidic-CH), 1711.8 (C=O), 1449.8 (C=N), 1072.2 (C-O-C). Anal. Calcd for
C24 H20 Cl2 N2 O8 : C, 53.85; H, 3.77; N, 5.23. Found: C, 53.80; H, 3.74; N, 5.21 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(3-nitro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (5h).
Yield 85%, [α]D25 = -11.1 (c 0.1 in DMSO), IR (KBr) cm−1 : 3424.8 (br, OH peak of carbohydrate residue),
2925.9 (N-H), 2851.8 (glucosidic-CH), 1711.8 (C=O), 1449.8 (C=N), 1089.8 (C-O-C). (EI-MS) m/z (%): 512
[M+ ](12), 349 (100), 163 (27), 161 (14), 77 (20). Anal. Calcd for C24 H21 N3 O10 : C, 56.36; H, 4.14; N, 8.22.
Found: C, 56.32; H, 4.15; N, 8.20 (%).
7-o-β-d-Glucopyranosyloxy-3-[3-(4-nitro phenyl)-1H-pyrazol-5-yl]-4H -chromen-4-one (5i).
Yield 83%, [α]2D5 = -9.4 (c 0.1 in DMSO), IR (KBr) cm−1 : 3455.4 (br, OH peak of carbohydrate residue), 2942.6
(N-H), 2849.9 (glucosidic-CH), 1720.1 (C=O), 1453.7 (C=N), 1099.1 (C-O-C). Anal. Calcd for C24 H21 N3 O10
C, 56.36; H, 4.14; N, 8.22. Found: C, 56.30; H, 4.10; N, 8.17 (%).
:
245

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Table 1. 1 H-NMR characterization data of the compounds 3a-i*; 4a-i**; 5a-i**
5''
3''
6''
2''
(3); R’=H
1
8
R'O
O
1''
3'
4'
(4); R’= -tetracetyl-β- -glucoside
(5); R’= Oβ- -glucoside D
2
4''
R
7
6
9
R:= (a) H;D(b) Cl (p);(c) Br (p);(d) CH3 (p);
(e) OCH3 (p); (f) Cl2 (o, p); (g) Cl2 (m,
p); (h) NO2 (m); (i) NO2 (p)
4
1'
N
2'
3
5'
10
N
H
5
O
Hydrogen/(δ)
3a-5a
7.45
7.46
7.47
7.50
7.55
7.57
6.47
6.50
6.52
6.36
6.42
6.40
12.4
12.2
12.4
6.34
6.44
6.44
3b-5b
7.50
7.54
7.27
7.49
7.59
7.60
6.45
6.49
6.54
6.37
6.42
6.39
12.4
12.4
11.9
6.41
6.37
6.39
3c-5c
7.46
7.46
7.49
7.51
7.56
7.58
6.41
6.51
6.52
6.33
6.44
6.40
12.3
12.1
12.1
6.42
6.39
6.38
3d-5d
7.50
7.44
7.51
7.49
7.58
7.60
6.40
6.48
6.51
6.32
6.41
6.40
11.8
11.7
11.8
6.41
6.34
6.44
3e-5e
7.48
7.45
7.45
7.51
7.61
7.59
6.48
6.57
6.57
6.35
6.39
6.41
11.9
11.7
11.8
6.38
6.33
6.41
3f-5e
7.51
7.48
7.48
7.51
7.64
7.58
6.42
6.53
6.54
6.39
6.35
6.39
11.9
11.5
12.1
6.38
6.38
6.39
–
3g-5g
7.45
7.47
7.46
7.50
7.58
7.61
6.43
6.51
6.55
6.34
6.38
6.41
12.1
11.5
11.7
6.49
6.44
6.38
3h-5h
7.47
7.49
7.47
7.49
7.54
7.58
6.45
6.49
6.51
6.41
6.40
6.48
11.8
12.8
11.4
6.38
6.47
6.55
3i-5i
7.48
7.44
7.46
7.48
7.52
7.60
6.44
6.52
6.53
6.37
6.40
6.40
11.9
11.8
11.8
6.44
6.38
6.47
H-2
(s)
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
H-5
(d)
H-6
(d)
H-8
(d)
H-1ꢀ
(s)
H-4ꢀ
(s)
7.51, d 7.44, d 7.36, d 7.36, d 7.35, d
7.49, d 7.41, d 7.40, d 7.38, d 7.37, d
7.50, d 7.42, d 7.38, d 7.37, d 7.36, d
7.41, s 8.45, s 7.70, d
7.40, s 8.42, s 7.73, d
7.39, s 8.41, s 7.71, d
H-2ꢀꢀ
H-3ꢀꢀ
H-4ꢀꢀ
H-5ꢀꢀ
H-6ꢀꢀ
–
–
7.29, t 7.32, d 7.48, d 7.10, d 6.80, d 7.30, s
7.27, t 7.30, d 7.45, d 7.11, d 6.78, d 7.32, s
7.28, t 7.32, d 7.43, d 7.08, d 6.81, d 7.28, s
–
–
–
–
–
–
–
8.21, d
–
8.19, d
–
8.20, d
7.20, t
7.18, t
7.22, t
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
8.12, d
8.10, d
8.14, d
–
–
–
7.29, t 7.32, d 7.48, d 7.10, d 6.80, d 7.20, d 7.24, d 7.54, t 8.21, d
7.27, t 7.30, d 7.45, d 7.11, d 6.78, d 7.18, d 7.27, d 7.53, t 8.19, d
7.28, t 7.32, d 7.43, d 7.08, d 6.81, d 7.23, d 7.25, d 7.59, t 8.20, d
7.51, d 7.44, d 7.36, d 7.36, d 7.35, d 7.35, d 7.32, d 7.90, d 7.70, d
7.49, d 7.41, d 7.40, d 7.38, d 7.37, d 7.33, d 7.30, d 7.91, d 7.73, d
7.50, d 7.42, d 7.38, d 7.37, d 7.36, d 7.35, d 7.31, d 7.89, d 7.71, d
246

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Table 1. Contunied
5''
6''
(3); R’=H
1
8
R'O
O
1''
3'
4'
(4); R’= -tetracetyl-β- -glucoside
(5); R’= Oβ- -glucoside D
2
4''
R
7
6
9
R:= (a) H;D(b) Cl (p);(c) Br (p);(d) CH3 (p);
(e) OCH3 (p); (f) Cl2 (o, p); (g) Cl2 (m,
p); (h) NO2 (m); (i) NO2 (p)
4
1'
N
3''
2''
2'
3
5'
10
N
H
5
O
Hydrogen/(δ)
H-1ꢀꢀꢀ
3a-5a 3b-5b 3c-5c 3d-5d
3e-5e
–
3f-5e 3g-5g 3h-5h 3i-5i
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
–
4.86
5.77
–
–
–
–
–
4.79
5.71
–
–
4.68
5.71
–
–
4.81
5.77
–
–
4.77
5.69
–
(d, 1H,
4.79
5.75
–
4.78
5.68
–
4.89
5.68
–
4.89
5.75
–
anomeric)
H-2ꢀꢀꢀ
(dd)
4.90
3.99
–
4.97
3.94
–
4.93
3.98
–
4.99
3.97
–
4.98
3.92
–
4.96
3.90
–
4.91
3.87
–
4.99
3.99
–
4.96
4.10
–
H-3ꢀꢀꢀ
(dd)
5.05
3.51
–
4.99
3.54
–
5.05
3.52
–
5.11
3.53
–
5.05
3.54
–
4.99
3.55
–
5.05
3.52
–
5.01
3.51
–
5.05
3.57
–
H-4ꢀꢀꢀ
(dd)
4.84
3.47
–
4.75
3.45
–
4.78
3.48
–
4.72
3.49
–
4.71
3.35
–
4.78
3.39
–
4.75
3.35
–
4.78
3.38
–
4.80
3.35
–
H-5ꢀꢀꢀ
(ddd, 1H)
4.34
3.71
–
4.34
3.88
–
4.41
3.84
–
4.49
3.88
–
4.48
3.90
–
4.44
3.79
–
4.47
3.88
–
4.40
3.89
–
4.45
3.64
–
H-6ꢀꢀꢀ
3.80-
4.29
3.49-
3.87
–
3.98-
4.32
3.44-
3.91
–
3.89-
4.29
3.50-
3.86
–
3.75-
4.29
3.59-
3.89
–
3.74-
4.29
3.45-
3.84
–
3.78-
4.27
3.47-
3.94
–
3.76-
4.34
3.59-
3.89
–
3.78-
4.29
3.38-
3.75
–
3.78-
4.29
3.45-
3.85
–
(m, 2H)
5
3
4
Acetyl
2.01,
1.95
1.99,
2.05
–
2.02,
1.96
1.94,
2.01
–
1.99,
1.94
1.98,
2.01
–
2.02,
1.94
1.98,
2.01
–
1.97,
1.98
1.97,
2.00
–
1.97,
1.98
1.99,
2.01
–
2.02,
1.98
1.94,
2.01
–
1.98,
1.97
1.99,
2.01
–
2.00,
1.97
1.96,
2.01
–
(s, 3H, 4OAc)
5
3
–
–
–
2.27
3.69
–
–
–
–
(CH3) (OCH3)
2.37 3.65
(CH3) (OCH3)
2.29 3.79
(CH3) (OCH3)
Group
4
4
5
–
–
–
–
–
–
–
–
–
–
–
–
–
–
(s, 3H)
Phenolic OH
(s)
3
4
5
5.12
4.90
5.10
5.01
4.87
5.03
4.91
4.94
4.95
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
–
*All compounds crystallized from DMF
**Majority of the compounds are syrupy in nature
247

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Table 2. 13 C-NMR characterization data of the compounds 3a-i; 4a-i; 5a-i
5''
6''
2''
(3); R’=H
1
8
R'O
O
1''
3'
4'
(4); R’= -tetracetyl-β- -glucoside
O
(5); R’= β- -glucoside D
2
4''
R
7
6
9
R:= (a) H;D(b) Cl (p);(c) Br (p);(d) CH3 (p);
(e) OCH3 (p); (f) Cl2 (o, p); (g) Cl2 (m,
p); (h) NO2 (m); (i) NO2 (p)
4
1'
N
3''
2'
3
5'
10
N
H
5
O
Carbon/(δ)
3a-5a 3b-5b 3c-5c 3d-5d 3e-5e 3f-5e 3g-5g 3h-5h 3i-5i
3
158.7
158.9
160.1
119.1
118.1
118.1
176.1
176.0
176.0
132.1
130.8
130.7
110.0
108.9
109.5
164.8
163.9
163.7
106.0
103.4
104.5
158.4
157.4
158.2
115.8
115.5
116.3
147.0
147.2
146.9
160.1
159.0
159.8
118.0
119.0
117.8
174.9
176.1
175.7
131.4
130.8
130.4
109.9
109.0
108.7
165.4
164.2
163.5
106.1
103.6
104.5
159.0
157.6
158.2
117.0
116.1
115.1
146.8
147.4
147.0
158.9
158.9
158.9
117.7
118.1
117.6
175.0
176.0
175.1
132.1
131.0
130.8
109.9
108.9
109.8
164.8
163.8
163.8
105.0
103.4
103.0
157.6
158.1
158.1
116.0
115.0
114.8
148.1
148.2
148.2
159.0
159.0
159.6
118.8
118.1
118.0
174.7
176.0
174.7
131.7
130.6
130.4
109.8
108.8
108.8
164.8
164.7
163.6
105.1
103.4
104.3
159.1
157.4
158.2
116.9
115.0
115.1
146.8
147.4
146.4
158.6 159.1 160.2
159.0 159.7 159.4
158.9 159.6 158.1
117.6 118.0 117.8
119.1 117.9 119.1
117.6 117.9 119.0
174.7 174.6 176.1
174.8 174.8 176.6
176.1 175.8 174.6
131.5 131.8 132.6
130.7 130.8 130.8
132.4 131.4 130.6
109.9 111.1 109.9
108.7 108.7 109.4
109.8 108.4 109.5
164.5 164.3 165.4
163.9 163.8 163.7
163.8 164.1 163.5
105.0 104.8 104.8
103.4 103.4 104.5
103.2 103.4 104.2
158.0 159.0 159.0
157.4 158.1 158.5
158.2 158.1 157.3
117.2 116.1 116.1
115.0 115.0 116.4
115.0 115.1 114.8
146.1 146.9 148.0
147.4 147.5 148.1
148.1 148.3 147.3
159.4 158.1
158.7 158.7
158.6 160.2
117.5 118.0
117.5 119.4
118.0 118.7
176.2 176.0
174.7 176.1
174.8 174.4
131.6 132.3
130.8 131.0
130.8 131.0
111.1 111.1
108.6 109.5
109.6 110.0
165.4 164.7
163.7 164.4
163.8 163.9
104.8 106.4
103.4 103.4
104.1 104.2
158.1 157.9
157.4 157.4
158.0 158.1
117.1 117.2
114.8 116.4
116.4 115.1
146.9 147.2
147.2 147.1
148.1 147.1
C-2
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
C-3
C-4
C-5
C-6
C-7
C-8
C-9
C-10
C-3ꢀ
248

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Table 2. Contunied.
5''
6''
(3); R’=H
1
8
R'O
O
1''
3'
4'
(4); R’= -tetracetyl-β- -glucoside
O
(5); R’= β- -glucoside D
2
4''
R
7
6
9
R:= (a) H;D(b) Cl (p);(c) Br (p);(d) CH3 (p);
(e) OCH3 (p); (f) Cl2 (o, p); (g) Cl2 (m,
p); (h) NO2 (m); (i) NO2 (p)
4
1'
N
3''
2''
2'
3
5'
10
N
H
5
O
Carbon/(δ)
3a-5a 3b-5b 3c-5c 3d-5d 3e-5e 3f-5e 3g-5g 3h-5h 3i-5i
3
102.1
102.1
101.9
144.1
143.4
143.1
133.6
133.6
133.8
128.0
127.1
127.0
129.0
128.8
128.6
128.1
128.1
127.9
129.0
128.8
128.6
128.0
127.1
127.0
–
102.0
102.6
103.6
143.0
143.1
142.9
131.6
133.2
133.2
128.1
127.0
128.0
128.6
128.9
128.9
135.1
133.6
134.9
128.6
128.9
128.9
128.1
127.1
128.0
–
102.8
102.5
102.0
144.0
143.1
144.2
131.7
131.6
131.7
129.1
128.9
128.5
131.5
131.4
131.2
123.0
122.8
123.0
131.5
131.4
131.3
129.1
129.4
129.3
–
102.4
102.0
103.1
142.7
143.1
143.0
131.5
131.4
131.6
126.7
126.4
126.5
128.4
128.0
128.4
138.0
138.1
137.8
128.4
128.2
128.4
126.7
126.6
126.4
–
102.1 101.7 102.0
102.0 102.0 102.1
102.3 102.1 102.0
143.5 143.2 143.1
143.1 143.2 143.2
143.1 144.2 143.0
124.8 127.6 132.1
128.7 127.5 131.0
128.8 127.6 131.1
127.9 132.9 129.0
127.6 132.9 129.1
127.6 132.7 129.0
115.1 130.5 134.1
115.4 130.4 134.1
115.1 130.2 134.0
161.1 135.2 132.9
161.3 135.0 132.5
161.1 135.6 132.8
115.1 127.0 131.0
115.1 127.2 131.0
115.0 126.9 130.8
127.9 130.0 127.4
127.6 130.2 127.4
127.8 130.1 127.2
102.1 102.0
102.3 102.2
102.0 102.0
144.0 143.1
143.0 143.2
142.9 143.2
133.3 139.5
133.1 139.4
133.1 139.2
121.7 129.4
121.6 129.3
121.6 129.5
149.2 120.9
149.0 120.8
149.1 120.9
120.6 147.6
120.5 147.3
120.3 147.5
130.0 120.9
130.3 120.6
130.2 120.7
133.0 129.4
133.4 129.2
133.2 129.4
C-4ꢀ
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
C-5ꢀ
C-1ꢀꢀ
C-2ꢀꢀ
C-3ꢀꢀ
C-4ꢀꢀ
C-5ꢀꢀ
C-6ꢀꢀ
C-1ꢀꢀꢀ
C-2ꢀꢀꢀ
–
–
–
–
–
101.8
104.7
–
102.4
106.1
–
102.5
106.2
–
102.6
104.9
–
101.7 101.7 101.7
104.8 104.0 104.8
101.7 102.5
106.0 104.6
–
–
–
–
–
72.1
72.2
72.3
72.1
72.1
75.2
72.1
75.3
72.1
75.1
72.1
75.2
72.2
75.3
75.7
75.2
75.0
75.0
249

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Table 2. Contunied.
5''
6''
(3); R’=H
1
8
R'O
O
1''
3'
4'
(4); R’= -tetracetyl-β- -glucoside
O
(5); R’= β- -glucoside D
2
4''
R
7
6
9
R:= (a) H;D(b) Cl (p);(c) Br (p);(d) CH3 (p);
(e) OCH3 (p); (f) Cl2 (o, p); (g) Cl2 (m,
p); (h) NO2 (m); (i) NO2 (p)
4
1'
N
3''
2''
2'
3
5'
10
N
H
5
O
Carbon/(δ)
3a-5a 3b-5b 3c-5c 3d-5d
3e-5e
–
3f-5e 3g-5g 3h-5h 3i-5i
3
–
70.5
77.3
–
–
71.0
77.0
–
–
70.9
77.0
–
–
71.0
77.8
–
–
–
–
–
C-3ꢀꢀꢀ
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
4
5
3
70.4
77.2
–
71.4
77.2
–
71.0
77.1
–
70.8
77.3
–
71.0
77.0
–
C-4ꢀꢀꢀ
C-5ꢀꢀꢀ
70.8
73.0
–
71.4
73.1
–
71.0
73.1
–
71.1
73.1
–
70.9
73.1
–
71.7
73.2
–
71.2
73.2
–
71.1
73.0
–
71.1
73.4
–
74.8
81.1
–
75.2
82.0
–
75.4
82.2
–
75.4
81.1
–
74.7
81.4
–
75.4
81.2
–
74.7
81.4
–
75.4
82.1
–
75.2
81.4
–
C-6ꢀꢀꢀ
64.9
66.4
–
66.1
64.8
–
66.1
64.6
–
65.7
66.0
–
66.1
64.8
–
66.4
64.7
–
66.0
64.8
–
65.1
64.8
–
65.4
66.6
–
Acetyl (CH3)
Acetyl (CO)
Group
20.4
–
20.5
–
21.1
–
20.7
–
20.7
–
21.8
–
20.4
–
21.8
–
20.8
–
–
–
–
–
–
–
–
–
–
169.6
–
170.3
–
170.0
–
170.6
–
170.4
–
171.0 171.0
170.0 170.0
–
–
–
–
–
–
–
–
–
–
–
23.4
56.2
(CH3) (OCH3)
23.7 56.2
(CH3) (OCH3)
23.7 56.1
(CH3) (OCH3)
4
4
5
–
–
–
–
–
–
–
–
–
–
–
–
–
–
*All compounds crystallized from DMF
**Majority of the compounds are syrupy in nature
Results and discussion
During the course of our present investigation 7-hydroxy-3-formyl-4H-chromen-4-one (1) was synthesized by
Vilsmeier-Haack reaction from resacetophenone.19,20 The reaction of 1 and substituted acetophenones in the
presence of freshly distilled piperidine in dry absolute alcohol for about 2 h resulted in the formation of 7-
250

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
hydroxy-3-(3-oxo-3-arylprop-1-enyl)-4H-chromen-4-ones (2a-i).19c,21 These compounds underwent on cycliza-
tion with hydrazine hydrate in aprotic solvent like DMF afforded 7-hydroxy-3-(3-aryl-1H-pyrazol-5-yl)-4H-
chromen-4-ones (3a-i).22 (Scheme 1).
5''
8
1
HO
HO
O
O
6''
4''
2
(a)
R
7
6
9
1'
CH CH 3'
R
2'
+
H3C
4
CHO
3''
3
10
1''
2''
5
O
R-
O
2a-i
(b)
O
O
a) H
1
b) Cl (p)
c) Br (p)
d) CH3 (p)
5''
3''
6''
2''
1
8
5
HO
R
O
1''
4'
3'
2
4''
e) OCH3 (p)
f) Cl2 (o, p)
g) Cl2 (m, p)
h) NO2 (m)
i) NO2 (p)
7
6
9
4
1'
N
2'
3
5'
10
N
H
O
3a-i
Scheme 1. Synthesis of 7-hydroxy-3-(3-aryl-1H -pyrazol-5-yl)-4H -chromen-4-ones (3a-i) (a) C5 H11 N, dry absolute
C2 H5 OH; (b) NH2 NH2 .H2 O, DMF.
o-Glucosydation23 of 3a-i (via its potassium salt) was carried out under anhydrous conditions using
2, 3, 4, 6-tetra-o-acetyl-α-d-glucopyranosyl bromide (TAGBr) as glucosyl donor in the presence of dode-
cyltrimethylammonium bromide (DTMAB) as a phase transfer catalyst. This reaction was carried out us-
ing anhydrous K2 CO3 in the mixture of DMF and acetone (3:2 v/v). This gave rise to 2, 3, 4, 6-tetra-o-
acetyl-α-d-glucopyranosyloxy-3-(3-aryl-1H-pyrazol-5-yl)-4H -chromen-4-ones (4a-i). The main advantage of
this reaction was that the distereoselectivity was high in favor of β-anomer, and improved the overall yield
and regioselectivity. Deacetylation of 4a-i with anhydrous zinc acetate in methanol afforded the desired 7-o-
β−d-glucopyranosyloxy-3-(3-aryl-1H-pyrazol-5-yl)-4H-chromen-4-ones (5a-i) (Scheme 2). The 1 H-NMR and
13 C-NMR characterization data of the compounds 3a-i, 4a-i, and 5a-i are given in Tables 1 and 2, respectively.
Biological activity
The title compounds were evaluated for their in vitro antibacterial activity against Escherichia coli, Kleb-
siella aerogenes, Staphylococcus aureus, and Bacillus subtilis and in vitro antifungal activity against Aspergillus
niger and Candida albicans fungi by the cup plate diffusion method. The comparative study of the 7-hydroxy-3-
(3-aryl-1H -pyrazol-5-yl)-4H-chromen-4-ones and 7-o-β−d-glucopyranosyloxy-3-(3-aryl-1H-pyrazol-5-yl)-4H-
chromen-4-ones was performed using the standard drugs ciprofloxacin and sulphacetamide for bacteria and gen-
tamycin and clotrimazole (100 ppm) for fungi. The test compounds were dissolved in DMSO at a concentration
of 100 ppm. The results of antimicrobial (antibacterial and antifungal) activity and anti-oxidant activity are
shown in Table 3. Most of the compounds exhibited mild to moderate antibacterial activity as well as antifungal
activity against all the microbes tested. In vitro free radical scavenging activities of glycosides were evaluated
by DPPH assay method and most of the compounds were found to be active at 1 mg/mL concentration. Per-
centage scavenging of DPPH radical was calculated using the formula: % Scavenging of DPPH = [(Control -
Test) / Control] × 100.
251

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
Table 3. Antimicrobial and antioxidant activity of 3a-i and 5a-i.
Zone of Inhibition (mm) (Activity Index) std
Antibacterial Activity
% Inhibition
Antioxidant
activity
Antifungal Activity
Gram-positive
Gram-negative
Compds
No
S. aureus
B. subtilis
E. coli
K. aerogenes
C. albicans
A. niger
DPPH
3a
3b
3c
3d
3e
3f
18 (0.56)*
20 (0.69)*
10 (0.29)*
07 (0.32)*
19 (0.90)*
11 (0.44)*
69.15 (0.70)*
(0.58)#
(0.76)#
(0.34)#
(0.33)#
(0.90)#
(0.46)#
19 (0.56)*
(0.61)#
16 (0.55)*
(0.62)#
16 (0.46)*
(0.55)#
11(0.50)*
(0.52)#
13 (0.62)*
(0.57)#
9 (0.36)*
(0.37)#
66.35 (0.68)*
58.56 (0.60)*
69.45 (0.71)*
64.12 (0.65)*
69.89 (0.71)*
67.12 (0.68)*
67.89 (0.69)*
62.51 (0.64)*
82.45 (0.84)*
88.73 (0.90)*
86.12 (0.88)*
91.65 (0.93)*
86.56 (0.88)*
80.94 (0.83)*
89.78 (0.92)*
87.45 (0.89)*
90.12 (0.92)*
98.03
14 (0.41)*
10 (0.34)*
13 (0.37)*
10 (0.45)*
19 (0.90)*
11(0.44)*
(0.45)#
(0.38)#
(0.45)#
(0.48)#
(0.83)#
(0.46)#
09 (0.26)*
(0.29)#
08 (0.28)*
(0.30)#
12 (0.34)*
(0.41)#
09 (0.41)*
(0.43)#
10 (0.48)*
(0.43)#
10 (0.40)*
(0.42)#
14 (0.41)*
11(0.38)*
13 (0.37)*
12 (0.55)*
18 (0.86)*
13 (0.52)*
(0.45)#
(0.42)#
(0.45)#
(0.57)#
0.78)
(0.54)#
#
(
11(0.32)*
(0.35)#
15 (0.52)*
(0.58)#
16 (0.46)*
(0.55)#
10 (0.45)*
(0.48)#
14 (0.66)*
12 (0.48)*
(0.50)#
(0.60)#
3g
3h
3i
14 (0.41)*
21 (0.72)*
21 (0.60)*
12 (0.55)*
18 (0.86)*
(0.78)#
13 (0.52)*
(0.45)#
(0.80)#
(0.72)#
(0.57)#
(0.54)#
20 (0.59)*
(0.65)#
18 (0.62)*
(0.69)#
20 (0.57)*
(0.69)#
14 (0.64)*
(0.67)#
17 (0.80)*
11 (0.44)*
(0.46)#
(0.74)#
18 (0.53)*
20 (0.69)*
19 (0.54)*
13 (0.59)*
19 (0.90)*
(0.83)#
12 (0.48)*
(0.58)#
(0.77)#
(0.66)#
(0.62)#
(0.50)#
5a
5b
5c
5d
5e
5f
31 (0.91)*
(1.00)#
24 (0.83)*
(0.92)#
22 (0.63)*
(0.76)#
22 (1.00)*
(1.04)#
27 (1.29)*
22 (0.88)*
(0.92)#
(1.17)#
33 (0.97)*
22 (0.76)*
20 (0.57)*
27 (1.23)*
25 (1.19)*
(1.07)#
23 (0.92)*
(1.06)#
(0.85)#
(0.69)#
(1.29)#
(0.96)#
30 (0.88)*
(0.97)#
27 (0.93)*
(1.04)#
19 (0.54)*
(0.66)#
24 (1.09)*
(1.14)#
30 (1.43)*
22 (0.88)*
(0.92)#
(1.30)#
25 (0.74)*
19 (0.66)*
17 (0.49)*
17 (0.77)*
20 (0.95)*
(0.87)#
16 (0.64)*
(0.81)#
(0.73)#
(0.59)#
(0.81)#
(0.66)#
31 (0.91)*
(1.00)#
23 (0.79)*
(0.88)#
23 (0.66)*
(0.79)#
20 (0.91)*
(0.95)#
23 (1.09)*
21 (0.84)*
(0.88)#
(1.00)#
29 (0.85)*
22 (0.76)*
23 (0.66)*
20 (0.91)*
26 (1.24)*
(1.13)#
20 (0.80)*
(0.94)#
(0.85)#
(0.79)#
(0.95)#
(0.83)#
5g
5h
5i
30 (0.88)*
(0.97)#
24 (0.83)*
(0.92)#
21 (0.60)*
(0.72)#
24 (1.09)*
(1.14)#
22 (1.05)*
26 (1.04)*
(1.08)#
(0.96)#
28 (0.84)*
26 (0.90)*
28 (0.80)*
21 (0.95)*
27 (1.29)*
(1.17)#
19 (0.76)*
(0.90)#
(1.00)#
(0.97)#
(1.00)#
(0.79)#
23 (0.68)*
(0.74)#
20 (0.69)*
(0.77)#
21 (0.60)*
(0.72)#
21 (0.95)*
(1.00)#
18 (0.85)*
22 (0.88)*
(0.92)#
(0.78)#
Std.1
Std. 2
34
31
29
26
35
29
22
21
21
23
25
24
(Activity index) = Inhibition zone of the sample / Inhibition zone of the standard, * = Activity index against Std. 1, # = Activity index against
Std. 2. For antibacterial activity: Std. 1 = Ciprofloxacin and Std. 2 = Sulphacetamide. For antifungal activity: Std. 1 = Gentamycin and Std. 2
= Clotrimazole. For anti-oxidant activity: Std. 1= Ascorbic Acid.
252

Synthesis, structural determination, and biological activity of new..., K. HATZADE, et al.,
+K-O
R
HO
R
O
O
O
(a)
N
N
N
N
H
N
3a-iH
OAc
H
O
O
H
H
(b)
O
AcO
AcO
R
O
H
H
OAc
R-
H
H
a) H
N
H
b) Cl (p)
c) Br (p)
O
4a-i
d) CH3 (p)
e) OCH3 (p)
f) Cl2 (o, p)
g) Cl2 (m, p)
h) NO2 (m)
i) NO2 (p)
OH
H
(c)
O
HO
HO
R
O
O
O
OH
H
H
N
N
5a-iH
Scheme 2. Synthesis of 7-o-β−d-glucopyranosyloxy-3-(3-aryl-1H -pyrazol-5-yl)-4H -chromen-4-ones (5a-i) (a) K2 CO3 ,
DMF, Acetone; (b) α-Acetobromoglucose, DTMAB; (c) Zn(OAc)2 , MeOH.
Conclusion
In the present work, we synthesized and evaluated the in vitro antimicrobial and anti-oxidant activity of the
newly synthesized glucosides of 7-hydroxy-3-(3-aryl-1H-pyrazol-5-yl)-4H-chromen-4-ones. Biological results
indicated that the new glucosides of 7-hydroxy-3-pyrazolyl chromones show greater pharmacological significance
than that of aglycons. Hence the compounds (5a-i) might be promising new antimicrobial as well as anti-oxidant
agents.
Acknowledgments
The authors are grateful to the Director, SAIF, Chandigarh and the Head, Department of Chemistry, IIT-Pawai,
Mumbai, for providing necessary spectral analysis; the Head, Department of Pharmaceutical Sciences, R T M
Nagpur University, Nagpur, for biological activity; and the Head, Department of Chemistry, R T M Nagpur
University, Nagpur, for providing necessary laboratory facilities.
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254