Synthesis of O-β-D-glucopyranosides of 7-hydroxy-3-(imidazol-2-yl)-4H- chromen-4-ones

DOI: 10.1080/07328300701298196

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Journal of Carbohydrate Chemistry p. 107 - 123 (2007)

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Authors:

Ingle Ingle

Hatzade Hatzade

Taile Taile

Gaidhane

Kharche Kharche

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Article abstract of DOI:10.1080/07328300701298196

The 7-hydroxy-3-formyl-4H-chromen-4-one 1 reacted with various cyclic 1,2-dicarbonyl compounds in the presence of ammonium acetate to furnish 7-hydroxy-3-([4,5-fused] imidazol-2-yl)-4H-chromen-4-ones 2a-f, which on glucosylation with -acetobromoglucose af

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Synthesis of O‐β‐D‐Glucopyranosides of

7‐Hydroxy‐3‐(imidazol‐2‐yl)‐4H‐chromen‐4‐ones

V. N. Ingle ^a, K. M. Hatzade ^a, V. S. Taile ^a, P. K. Gaidhane ^a& S. T. Kharche

^aDepartment of Chemistry , Rashtrasant Tukadoji Maharaj Nagpur

University , Nagpur, 440033, India

Published online: 09 May 2007.

To cite this article: V. N. Ingle , K. M. Hatzade , V. S. Taile , P. K. Gaidhane & S. T. Kharche (2007) Synthesis

of O‐β‐D‐Glucopyranosides of 7‐Hydroxy‐3‐(imidazol‐2‐yl)‐4H‐chromen‐4‐ones, Journal of Carbohydrate

Chemistry, 26:2, 107-123, DOI: 10.1080/07328300701298196

To link to this article: http://dx.doi.org/10.1080/07328300701298196

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Journal of Carbohydrate Chemistry, 26:107–123, 2007

ISSN: 0732-8303 print 1532-2327 online

DOI: 10.1080/07328300701298196

Synthesis of O-b-D-

Glucopyranosides of

7-Hydroxy-3-(imidazol-2-yl)-

4H-chromen-4-ones

V. N. Ingle, K. M. Hatzade, V. S. Taile, P. K. Gaidhane, and

S. T. Kharche

Department of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur,

India

The 7-hydroxy-3-formyl-4H-chromen-4-one 1 reacted with various cyclic 1,2-dicarbonyl

compounds in the presence of ammonium acetate to furnish 7-hydroxy-3-([4,5-fused]

imidazol-2-yl)-4H-chromen-4-ones 2a–f, which on glucosylation with a-acetobromoglu-

cose affords 2,3,4,6-tetra-O-acetyl-b-D-glucopyranosyloxy-3-([4,5-fused] imidazol-2-yl)-

4H-chromen-4-ones 3a–f. 7-O-b-D-Glucopyranosyloxy-3-([4,5-fused] imidazol-2-yl)-

4H-chromen-4-ones 4a–f were prepared by deacetylation with anhydrous zinc acetate

in absolute methanol. The structure of these new O-b-D-glucosides was established on

the basis of chemical, elemental, and spectral analysis. These compounds were evalu-

ated for their in vitro biological activity.

Keywords Chromone, Imidazoles, a-Acetobromoglucose, Glucosylation, O-b-D-

Glucosides

Received February 8, 2007; accepted February 23, 2007.

Address correspondence to K. M. Hatzade, Department of Chemistry, Rashtrasant

Tukadoji Maharaj Nagpur University, Nagpur 440033, India. E-mail: g_kishor2000@

yahoo.co.in

107

V. N. Ingle et al.

108

INTRODUCTION

Fused heterocyclic compounds are common in nature, and they are also used as

drugs to treat a wide variety of illness.^[1]The fused-ring heterocycles have gen-

erally similar properties to those of the simple heterocycles (e.g., benzimidazole

exhibiting diverse pharmaceutical and industrial applications). They are found

to possess anthelmintic, insecticidal, antibacterial, antiviral, antiamoebic

antifungal, antiparasitic, and antihistamine activities.^[2–6]On the other

hand, ﬂavonoids are based on the ﬂavone and related ring systems and consti-

tute an important class of widely distributed plant secondary metabolites. In

addition to the various functions of ﬂavonoids in plants, several therapeutically

interesting biological activities of certain ﬂavonoids have been reported includ-

ing anticancer, anti-HIV, and antioxidant properties,^[7]and insect antifeedant

activity.^[8]Similarly, carbohydrates are being considered as extremely useful

stereochemical building blocks for complex organic synthesis. Glycoconjugates

exert important roles in many biological processes,^[9–11]including particularly

cellular recognition in the case of immune response,^[12,13]tumor metastasis,^[14]

inﬂammation,^[15–17]and bacterial and viral infections.^[9]The great importance

of this category of heterocycles and glycoconjugates and in continuation of our

research work on chromone-based heterocycles and their ^O-b-D-glucosides

oriented our attention to the synthesis of a series of new heterocyclic deriva-

tives combining chromone, fused imidazole, and glucose residue in one molecu-

lar frame as new possible biological active compounds. Herein we report the

synthesis and biological activity of chromones bearing a fused imidazole ring

at position 3 and carbohydrate moiety at position 7, starting from the

7-hydroxy-3-formyl-4H-chromen-4-one.

RESULTS AND DISCUSSION

During the course of our present investigation, the starting material, namely,

7-hydroxy-3-formyl-4H-chromen-4-one 1, was prepared from resacetophenone

according to the method described previously.^[18]This compound 1 on conden-

sation^[19]with various cyclic 1,2-dicarbonyl compounds like 1,2-cyclohexa-

dione, 1,2-naphthoquinone, 9,10-phenanthroquinone, etc., in the presence of

ammonium acetate in glacial acetic acid leads to the formation of 7-hydroxy-

3-([4,5-fused] imidazol-2-yl)-4H-chromen-4-ones 2a–f. The IR spectrum of 2a

showed a broad peak at 3451 cm²¹due to the OH stretch. The peaks at 2958

and 2361 cm²¹appeared due to NH and Ar-CH stretches, respectively. A

strong absorption at 1626 cm²¹was assigned to C55O stretch. The peaks at

1458 and 1102 cm²¹were due to C55N and C-O-C ether linkage stretches,

respectively. The H NMR spectrum of the said compound showed the peaks

at d 1.58 (m, 5⁰-2H, 6⁰-2H) (CH₂), 2.46 (t, 4⁰-2H, 7⁰-2H) (CH₂), 5.00 (s, 1H,

-OH), 6.34–7.51 (m, 3H, Ar-H), 7.60 (s, 2-H, CH) and 11.2 (s, 1⁰-H, N-H).

Synthesis of O-b-D-glucopyranosides

109

Scheme 1: Synthesis of 7-hydroxy-3-([4, 5-fused] imidazol-2-yl)-4H-chromen-4-ones 2; (i)

CH₃COONH₄, CH₃COOH.

There was no peak due to -CHO group (Sch. 1). ¹³C NMR data also supported

the assigned structure.

a-Acetobromoglucose acts as a glucosyl donor for the glucosylation and

was synthesized from pentacetylated derivative of glucose by a known

method. Glucosylation^[20]of potassium salt of 2a–f has been carried out

using a-acetobromoglucose under argon atmosphere in anhydrous acetonitrile

in the presence of 18-crown-6 ether as a catalyst and afforded 2, 3, 4, 6-tetra-O-

acetyl-7-^O-b-D-glucopyranosyloxy-3-([4,5-fused] imidazol-2-yl)-4H-chromen-4-

ones 3a–f in high yield. The absence of an IR band at 3100–3500 cm²¹(due

to OH stretch) indicated the formation of product 3a. Further, the peaks at

2954 and 2363 cm²¹were due to the NH and Ar-CH stretches. The C55O

stretch peak was found to be shifted to 1721 cm²¹. A strong absorption at

1760 cm²¹was assigned to the C55O stretch of O-acetyl groups of glucose

moiety. The peak at 1051 cm²¹was attributed to the C-O-C stretch. A sharp

peak at 2854 cm²¹was assigned to glucosidic CH stretch. In particular, in

the H NMR spectrum of 3a, the anomeric proton H-1 appeared as a doublet

at d 4.76 with a coupling of (J_1,2¼ 7.9 Hz). This relatively large coupling

constant is characteristic for a b-D-glucopyranoside. Similarly, ¹³C data of

the acetylated b-glucosides 3a–f were in agreement with the assigned struc-

tures. We tried to deacetylate 3a–f by standard procedure using NaOMe-

MeOH;^[21]however, we found that the strong basic condition resulted in

cleavage of the isoﬂavone’s C-ring, while the Zn(OAc)₂/MeOH system led to

signiﬁcant deglycosylation. Finally, complete deacetylation of 3a–f was

achieved by using anhydrous Zn(OAc)₂in methanol^[22]in good yield (Sch. 2).

The IR spectrum of 4a showed the presence of characteristic absorption

V. N. Ingle et al.

110

Scheme 2: Synthesis of 7-O-b-D-glucopyranosyloxy-3-([4,5-fused] imidazol-2-yl)-4H-chromen-

4-ones 4; (i) K₂CO₃, CH₃CN, Ar atmosphere; (ii) a-acetobromoglucose, 18-crown-6; (iii)

Zn(CH₃COO)₂, MeOH.

peaks at 3412 (br, OH peak of carbohydrate residue), 2928 (NH), 2853 (glucosi-

dic-CH), 2362 (Ar-CH), 1599 (C55O), 1445 (C55N), and 1089 (C-O-C) cm²¹, indi-

cating the formation O-b-D-glucoside. This was also conﬁrmed by its ¹H NMR,

¹³C NMR, and EI-MS data. The H and ¹³C NMR data show the presence of

carbohydrate moiety. The chemical shifts of the anomeric proton show

b-linkage at d 5.74 (J_1,2¼ 8.4 Hz), indicating the linkage of the carbohydrate

unit to the C-7 position of the aglycone. Compound 4a exhibited NH at d

11.2 ppm, aromatic protons at d 6.36–7.49, and the characteristic pyranosyl

ring protons at d 3.44–4.72. In the EI-MS study, the molecular ion peak at

m/z 445 [M þ 1]^þwas dominated by m/z 282 (100%) with the loss of 163 amu

corresponding to the loss of an intact anhydro-sugar moiety. Also, the

Synthesis of O-b-D-glucopyranosides

111

molecular ion at m/z 445 [M þ 1]^þconﬁrms the molecular formula of the corre-

sponding glucoside. All the compounds gave satisfactory C, H, and N analysis.

BIOLOGICAL RESULTS

Antimicrobial activities of the prepared compounds were tested against bacteria,

such as Escherichia coli, Klebisilla aerogens, Staphylococcus aureus, Bacillus

substilis and fungi, Aspergillus niger and Candida albicans using the cup

plate diffusion method. Ciproﬂoxacin and sulphacetamide for bacteria and gen-

tamycin and clotrimazole for fungi were used as reference drugs. The results of

tested compounds against bacteria and fungi are shown in Table 1.

As shown in Table 1, the glucosides had higher antimicrobial activity

against Gram-positive and Gram-negative bacteria and fungi than that of

aglycones. The results of antibacterial activities indicated that slight difference

between the activities of all the glucosides against tested bacteria. The com-

pounds 4a–f showed very high antibacterial activity against this bacterium.

Similarly, the results of antifungal activity revealed that the glucosides had

promising antifungal activities against two yeast strains (C. albicans and

A. niger). These results suggested that glucosides had effective and selective

antimicrobial activities against both bacteria and fungi.

Table 1 also summarizes free radical scavenging activity (antioxidant

activity) using the DPPH assay method. According these results, the newly

synthesized glucosides had more promising antioxidant activities.

CONCLUSION

In conclusion, the condensation of 7-hydroxy-3-formyl-4H-chromen-4-one

with various cyclic 1,2-dicarbonyl compounds in the presence of ammonium

acetate followed by glucosydation with a-acetobromoglucose as a glucosyl

donor afforded 7-O-b-D-glucopyranosyloxy-3-([4,5-fused] imidazol-2-yl)-4H-

chromen-4-ones 4a–f in quite good yield. These synthesized compounds

were evaluated in vitro antimicrobial activity and antioxidant activity.

According to the in vitro results, the new glucosides of 7-hydroxy-3-imidazolyl

chromones had commonly of greater pharmacological signiﬁcance. The com-

pounds 4a–f might be promising candidates of new antibacterial as well as

antioxidant agents.

EXPERIMENTAL

General

FT-IR spectra were recorded on a Perkin-Elmer spectrum Rx-I spectropho-

tometer. H NMR and ¹³C NMR spectra were obtained on a Bruker II-400

Table 1: Data for in vitro antimicrobial and antioxidant activity of compounds 4a–f.

Diameter of zone of inhibition (mm) (activity index)^std

Antibacterial

% Inhibition

antioxidant

Antifungal

Compd

S. aureus

B. substilis

E. coli

K. aerogens

C. albicans

A. niger

DPPH

22 (0.67)^a(0.71)^b22 (0.76)^a(0.85)^b19 (0.54)^a(0.65)^b18 (0.82)^a(0.86)^b28 (1.33)^a(1.22)^b20 (0.80)^a(0.83)^b81.15 (0.83)^a

20 (0.59)^a(0.64)^b21 (0.72)^a(0.81)^b20 (0.57)^a(0.69)^b18 (0.82)^a(0.86)^b25 (1.19)^a(1.09)^b19 (0.76)^a(0.79)^b81.11 (0.83)^a

21 (0.62)^a(0.68)^b20 (0.69)^a(0.77)^b21 (0.60)^a(0.72)^b18 (0.82)^a(0.86)^b29 (1.38)^a(1.26)^b21 (0.84)^a(0.88)^b77.52 (0.79)^a

18 (0.53)^a(0.58)^b18 (0.62)^a(0.69)^b20 (0.57)^a(0.69)^b15 (0.68)^a(0.71)^b29 (1.38)^a(1.26)^b14 (0.56)^a(0.58)^b86.44 (0.88)^a

20 (0.59)^a(0.64)^b19 (0.66)^a(0.73)^b21 (0.60)^a(0.72)^b19 (0.86)^a(0.90)^b29 (1.38)^a(1.26)^b17 (0.68)^a(0.71)^b75.67 (0.77)^a

17 (0.50)^a(0.55)^b20 (0.69)^a(0.77)^b24 (0.69)^a(0.83)^b16 (0.77)^a(0.81)^b22 (1.05)^a(0.96)^b22 (0.88)^a(0.92)^b75.82 (0.77)^a

25 (0.74)^a(0.81)^b34 (1.17)^a(1.31)^b20 (0.57)^a(0.69)^b20 (0.91)^a(0.95)^b31 (1.48)^a(1.35)^b21 (0.84)^a(0.88)^b84.45 (0.86)^a

29 (0.85)^a(0.94)^b24 (0.83)^a(0.92)^b21 (0.60)^a(0.72)^b19 (0.86)^a(0.90)^b30 (1.43)^a(1.30)^b22 (0.88)^a(0.92)^b78.12 (0.80)^a

28 (0.82)^a(0.90)^b37 (1.28)^a(1.42)^b24 (0.69)^a(0.83)^b24 (1.09)^a(1.14)^b34 (1.62)^a(1.48)^b23 (0.92)^a(0.96)^b89.25 (0.91)^a

20 (0.59)^a(0.65)^b23 (0.79)^a(0.88)^b22 (0.63)^a(0.76)^b17 (0.77)^a(0.81)^b36 (1.71)^a(1.57)^b22 (0.88)^a(0.92)^b80.78 (0.82)^a

23 (0.68)^a(0.74)^b17 (0.59)^a(0.65)^b35 (1.00)^a(1.21)^b20 (0.91)^a(0.95)^b32 (1.52)^a(1.39)^b21 (0.84)^a(0.88)^b81.01 (0.83)^a

19 (0.56)^a(0.61)^b25 (0.86)^a(0.96)^b33 (0.94)^a(1.14)^b17 (0.77)^a(0.81)^b25 (1.19)^a(1.09)^b23 (0.92)^a(0.96)^b78.25 (0.80)^a

Std.1

Std. 2

98.03

(Activity index) ¼ Inhibition zone of the sample/inhibition zone of the standard.

^aActivity index against std. 1.

^bActivity index against std. 2.

For antibacterial activity: Std. 1 ¼ ciproﬂoxacin and Std. 2 ¼ sulphacetamide. For antifungal activity: Std. 1 ¼ gentamycin and

Std. 2 ¼ clotrimazole. For antioxidant activity: Std. 1¼ ascorbic acid.

Synthesis of O-b-D-glucopyranosides

113

NMR spectrophotometer (¹H, 400 MHz and ¹³C, 100 MHz), using TMS as an

internal standard in DMSO-d₆, Chemical shifts (d) were measured in ppm.

Multiplicity was simpliﬁed such as s ¼ singlet, d ¼ doublet, t ¼ triplet, and

m ¼ multiplet. Mass spectra were determined on a Hitachi Perkin-Elmer

RMU 6D mass spectrometer. Optical rotations were recorded at the sodium

D line and ambient temperature with a JASCO digital polarimeter. Elemental

analyses were performed on a Perkin-Elmer 2400 CHN analyzer instrument.

Purity of the compounds was checked on silica gel plates using iodine vapor

as a visualizing agent. Melting points measured in open capillary tubes were

uncorrected. The solvents and various essential reagents were puriﬁed and

dried according to recommended procedures. Various cyclic 1,2-dicarbonyl com-

pounds like 1,2-cyclohexadione, 1,2-naphthoquinone, and 9,10-phenanthren-

quinone were prepared according to the method described previously.^[23,24]

7-Hydroxy-3-formyl-4H-chromen-4-one (1)

In dry DMF (121 mL) in a three-necked ﬂask, POCl₃(75 mL, 0.49 mol) was

added slowly with vigorous stirring at 508C. Heating and stirring was contin-

ued for 2 h at 45–558C. The solution of resacetophenone (18.24 g, 0.12 mol)

in DMF (25 mL) was then slowly added with stirring at 508C and the stirring

was continued for 2 h. After cooling, the mixture was kept overnight at rt

and diluted slowly by adding ice-cold water (500 mL) and stirred again for

6 h. The red crystalline product obtained was ﬁltered off and recrystallized

from alcohol, m.p. 2698C, yield 45 g (78%). Its alcoholic solution gives violet

coloration with neutral FeCl₃. IR (KBr): v 3428 (phenolic OH), 3087, 2363

(Ar-CH), 2773 (CH in CHO), 1685 (C55O), 1614 (C55C), 1093 (C-O-C) cm²¹

;

¹H NMR (400 MHz, DMSO-d₆): d 4.95 (s, 1H, -OH), 6.35–7.5 (m, 3H, Ar-H),

8.05 (s, 2-H, CH), 9.59 (s, 1H, CHO); ¹³C NMR (100 MHz, DMSO-d₆): 104.8

(s, C-8), 109.4 (s, C-6), 114.0 (s, C-10), 121.7 (s, C-3, C-CHO), 131.4 (s, C-5),

157.9 (s, C-9), 161.2 (s, C-7), 171.0 (s, C-2), 174.9 (s, C-4, C55O), 188.1

(s, CHO of C-3).

General Procedure for the Preparation of 7-Hydroxy-3-

([4, 5-fused] imidazol-2-yl)-4H-chromen-4-ones (2)

A mixture of 7-hydroxy-3-formyl-4H-chromen-4-one (5 mmol), cyclic 1,

2-dicarbonyl compounds (5 mmol), ammonium acetate (10 mmol), and glacial

acetic acid (50 mL) was reﬂuxed for 2 h. It was poured in to cold water

(200 mL). The solid obtained was ﬁltered, washed with water, and crystallized

from solvents.

V. N. Ingle et al.

114

7-Hydroxy-3-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-2-yl)-4H-

chromen-4-one (2a)

Yield 67%; mp 2958C (ethanol); IR (KBr): 3451 (br, OH), 2958 (NH), 1625

(C55O), 1457 (C55N), 1102 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 1.58

(m, 5⁰-2H, 6⁰-2H) (CH₂), 2.46 (t, 4⁰-2H, 7⁰-2H) (CH₂), 5.00 (s, 1H, OH), 6.34–

7.51 (m, 3H, Ar-H), 7.60 (s, 2-H, CH), 11.2 (s, 1⁰-H, NH); ¹³C NMR (100 MHz,

DMSO-d₆): 20.1 (s, C-5⁰, C-6⁰), 26.9 (s, C-4⁰, C-7⁰), 104.0 (s, C-8), 111.8 (s, C-6),

115.1 (s, C-10), 118.6 (s, C-3), 124.8 (s, C-8⁰, C-9⁰), 132.0 (s, C-5), 135.7

(s, C-2⁰), 158.7 (s, C-9), 159.3 (s, C-2), 163.5 (s, C-7), 175.8 (s, C-4, C55O); MS

(EI, 70 eV): m/z (%) 282 (M^þ, 100), 161 (19), 91 (28).

Anal. Calcd. for C₁₆H₁₄N₂O₃(282): C, 68.07; H, 5.00; N, 9.92. Found: C,

68.06; H, 4.95; N, 9.91.

7-Hydroxy-3-(3H-naphtho[2,1-d]imidazol-2-yl)-4H-chromen-4-one (2b)

Yield 76%; mp 2998C (chloroform þ dioxane); IR (KBr): 3400(br, OH), 2989

(NH), 1627 (C55O), 1458 (C55N), 1103 (C-O-C); ¹H NMR (400 MHz,

DMSO-d₆): d 4.95 (s, 1H, OH), 6.35–7.75 (m, 9H, Ar-H), 7.52 (s, 2-H, CH),

12.3 (s, 1⁰-H, NH); ¹³C NMR (100 MHz, DMSO-d₆): 105.5 (s, C-8), 110.1

(s, C-6), 114.9 (s, C-9⁰), 115.0 (s, C-12⁰), 116.2 (s, C-10), 118.9 (s, C-3), 123.1

(s, C-13⁰), 123.4 (s, C-8⁰), 127.1 (s, C-4⁰, C-7⁰), 127.9 (s, C-5⁰, C-6⁰), 131.0

(s, C-5), 139.1 (s, C-10⁰), 141.4 (s, C-2⁰), 142.1 (s, C-11⁰), 157.8 (s, C-9), 158.9

(s, C-2), 164.5 (s, C-7), 176.1 (s, C-4, C55O); MS (EI, 70 eV): m/z (%) 328 (M^þ,

100), 161 (22), 91 (29).

Anal. Calcd. for C₂₀H₁₂N₂O₃(328): C, 73.14; H, 3.67; N, 8.52. Found: C,

73.16; H, 3.68; N, 8.53.

7-Hydroxy-3-(1H-phenanthro[9,10-d]imidazol-2-yl)-4H-chromen-4-one

(2c)

Yield 80%; mp 3268C (ethanol); IR (KBr): 3429 (br, OH), 2925 (NH), 2361

(Ar-CH), 1624 (C55O), 1506 (C55N), 1095 (C-O-C); ¹H NMR (400 MHz,

DMSO-d₆): d 5.02 (s, 1H, OH), 6.37–9.01 (m, 11H, Ar-H), 7.50 (s, 2-H, CH),

11.2 (s, 1⁰-H, NH); ¹³C NMR (100 MHz, DMSO-d₆): 104.8 (s, C-8), 110.1

(s, C-6), 115.9 (s, C-10), 117.6 (s, C-3), 123.1 (s, C-7⁰, C-8⁰), 126.4 (s, C-5⁰, C-6⁰,

C-9⁰, C-10⁰), 126.8 (s, C-13⁰, C-14⁰), 127.7 (s, C-12⁰, C-15⁰), 128.8 (s, C-4⁰,

C-11⁰), 131.6 (s, C-16⁰, C-17⁰), 131.9 (s, C-5), 141.0 (s, C-2⁰), 157.5 (s, C-9),

160.0 (s, C-2), 165.1 (s, C-7), 174.8 (s, C-4, C55O); MS (EI, 70 eV): m/z (%)

378 (M^þ, 100), 217 (27), 163 (44), 91 (29).

Anal. Calcd. for C₂₄H₁₄N₂O₃(378): C, 76.18; H, 3.73; N, 7.40. Found: C,

76.15; H, 3.71; N, 7.38.

Synthesis of O-b-D-glucopyranosides

115

3-(3,4,-Dihydroimidazo[4,5-b]indol-2-yl)-7-hydroxy-4H-chromen-4-one

(2d)

Yield 79%; mp 3158C (chloroform þ dioxane); IR (KBr): 3412 (br, OH), 2986

(NH), 1631 (C55O), 1456 (C55N), 1160 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆):

d 4.94 (s, 1H, OH), 6.29–7.55 (m, 7H, Ar-H), 7.57 (s, 2-H, CH), 10.7 (s, 8⁰-H,

NH), 11.8 (s, 1⁰-H, NH); ¹³C NMR (100 MHz, DMSO-d₆): 106.1 (s, C-8), 109.8

(s, C-6), 110.9 (s, C-7⁰), 117.0 (s, C-10), 117.9 (s, C-3), 118.8 (s, C-4⁰), 120.2

(s, C-6⁰), 120.5 (s, C-11⁰), 122.0 (s, C-5⁰), 133.1 (s, C-5), 135.1 (s, C-12⁰), 135.9

(s, C-2⁰), 136.2 (s, C-10⁰), 143.0 (s, C-9⁰), 157.9 (s, C-9), 159.4 (s, C-2), 164.9

(s, C-7), 175.2 (s, C-4, C55O); MS (EI, 70 eV): m/z (%) 317 (M^þ, 100), 161 (27),

91 (29).

Anal. Calcd. for C₁₈H₁₁N₃O₃(317): C, 68.14; H, 3.49; N, 13.24. Found: C,

68.12; H, 3.48; N, 13.23.

3-(7-Bromo-3,4,-dihydroimidazo[4,5-b]indol-2-yl)-7-hydroxy-4H-

chromen-4-one (2e)

Yield 68%; mp 2968C (chloroform þ dioxane); IR (KBr): 3447 (br, OH), 2995

(NH), 1621 (C55O), 1457 (C55N), 1154 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆):

d 4.94 (s, 1H, OH), 6.35–7.75 (m, 6H, Ar-H), 7.57 (s, 2-H, CH), 10.0 (s, 8⁰-H,

NH), 11.2 (s, 1⁰-H, NH); ¹³C NMR (100 MHz, DMSO-d₆): 106.1 (s, C-8), 109.8

(s, C-6), 113.0 (s, C-7⁰), 117.0 (s, C-10), 117.2 (s, C-5⁰), 117.9 (s, C-3), 120.8

(s, C-4⁰), 121.0 (s, C-6⁰), 122.2 (s, C-11⁰), 133.1 (s, C-5), 134.1 (s, C-12⁰), 135.8

(s, C-2⁰), 136.8 (s, C-10⁰), 143.2 (s, C-9⁰), 157.9 (s, C-9), 159.4 (s, C-2), 164.9

(s, C-7), 175.2 (s, C-4, C55O).

Anal. Calcd. for C₁₈H₁₀BrN₃O₃(396): C, 54.17; H, 2.54; N, 10.61. Found: C,

54.16; H, 2.52; N, 10.60.

7-Hydroxy-3-(7-nitro-3,4,-dihydroimidazo[4,5-b]indol-2-yl)-4H-

chromen-4-one (2f)

Yield 65%; mp 3058C (ethanol); IR (KBr): 3443 (br, OH), 2987 (NH), 1624

(C55O), 1452 (C55N), 1166 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 4.94

(s, 1H, OH), 6.38–8.50 (m, 6H, Ar-H), 7.57 (s, 2-H, CH), 9.10 (s, 8⁰-H, NH),

11.8 (s, 1⁰-H, NH); ¹³C NMR (100 MHz, DMSO-d₆): 106.1 (s, C-8), 109.8

(s, C-6), 112.2 (s, C-7⁰), 114.1 (s, C-6⁰), 115.8 (s, C-4⁰), 117.0 (s, C-10), 117.9

(s, C-3), 121.5 (s, C-11⁰), 133.1 (s, C-5), 135.4 (s, C-2⁰), 135.9 (s, C-10⁰), 141.0

(s, C-5⁰), 141.8 (s, C-12⁰), 142.0 (s, C-9⁰), 157.9 (s, C-9), 159.4 (s, C-2), 164.9

(s, C-7), 175.2 (s, C-4, C55O).

Anal. Calcd. for C₁₈H₁₀N₄O₅(362): C, 59.67; H, 2.78; N, 15.46. Found: C,

59.68; H, 2.80; N, 15.14.

V. N. Ingle et al.

116

General Procedure for the Preparation of 2,3,4,6-Tetra-

O-acetyl-7-O-b-^D-glucopyranosyloxy-3-([4,5-fused]

imidazol-2-yl)-4H-chromen-4-ones (3)

A mixture of 7-hydroxy-3-([4, 5-fused] imidazol-2-yl)-4H-chromen-4-ones

(0.39 mmol), K₂CO₃(0.43 mmol), and acetonitrile (50 mL) was stirred at rt

under argon atmosphere. 18-Crown-6 (10 mg, 0.04 mmol) was added followed

by a-acetobromoglucose (0.245 g, 0.58 mmol). After 5 h, it was poured into ice

cold water and neutralized with H₂SO₄(1 mol/L). The product was extracted

in ethyl acetate (50 mL ꢀ 4). Removal of the volatiles under reduced

pressure afforded residue was puriﬁed by silica gel ﬂash chromatography

(ethyl acetate:petroleum ether 1:2 v/v) to give a brown coloured semisolid.

2,3,4,6-Tetra-O-acetyl-7-O-b-D-glucopyranosyloxy-3-(4,5,6,7-tetrahydro-

1H-benzo[d]imidazol-2-yl)-4H-chromen-4-one (3a)

Yield 79%; [a]²_D⁵¼ 27.9 (c 0.1, CH₃OH); IR (KBr): 2954 (NH), 2854 (gluco-

sidic CH), 2365 (Ar-CH), 1761 (C55O of O-acetyl gps of glycone moiety), 1722

(C55O), 1646 (C55N), 1052 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 1.59

(m, 5⁰-2H, 6⁰-2H) (CH₂), 2.01, 1.95, 1.99, 2.05 (s, 3H, OAc), 2.58 (t, 4⁰-2H,

7⁰-2H) (CH₂), 3.86–4.24 (m, 2H, 6⁰⁰-H), 4.39 (dd, 1H, 5⁰⁰-H), 4.76 (d, 1H, 1⁰⁰-H,

anomeric proton), 4.87–5.00 (m, 3H, 2⁰⁰,3⁰⁰,4⁰⁰-H), 6.38–7.49 (m, 3H, Ar-H),

7.51 (s, 2-H, CH), 11.8 (s, 1⁰-H, N-H); ¹³C NMR (100 MHz, DMSO-d₆): 21.8

(s, C-atom, CH₃of Acetyl group), 22.4 (s, C-5⁰, C-6⁰), 25.8 (s, C-4⁰, C-7⁰), 66.1

(s, C-6⁰⁰), 71.1 (s, C-3⁰⁰), 71.5 (s, C-4⁰⁰), 72.8 (s, C-2⁰⁰), 74.9 (s, C-5⁰⁰), 101.9

(s, C-1⁰⁰, anomeric C-atom), 103.9 (s, C-8), 109.1 (s, C-6), 115.6 (s, C-10), 118.2

(s, C-3), 125.1 (s, C-8⁰, C-9⁰), 131.2 (s, C-5), 135.5 (s, C-2⁰), 157.9 (s, C-9),

159.8 (s, C-2), 163.9 (s, C-7), 171.0 (s, C-atoms of Acetyl C55O), 174.9 (s, C-4,

C55O).

Anal. Calcd. for C₃₀H₃₂N₂O₁₂(613): C, 58.82; H, 5.27; N, 4.57. Found: C,

58.90; H, 5.26; N, 4.55.

2,3,4,6-Tetra-O-acetyl-7-O-b-D-glucopyranosyloxy-3-(3H-naphtho [2,1-d]

imidazol-2-yl)-4H-chromen-4-one (3b)

Yield 88%; [a]²_D⁵¼ 26.0 (c 0.1, CH₃OH); IR (KBr): 2935 (NH), 2882 (gluco-

sidic CH), 2364 (Ar-CH), 1758 (C55O of O-acetyl gps of glycone moiety), 1727

(C55O), 1624 (C55N), 1055 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 2.02,

1.96, 1.98, 2.04 (s, 3H, OAc), 3.90–4.21 (2H, m, 6⁰⁰-H), 4.40 (1H, dd, 5⁰⁰-H),

4.71 (1H, d, 1⁰⁰-H, anomeric proton), 4.85–5.04 (3H, m, 2⁰⁰,3⁰⁰,4⁰⁰-H), 6.34–7.72

(m, 9H, Ar-H), 7.53 (s, 2-H, CH), 11.6 (s, 1⁰-H, N-H); ¹³C NMR (100 MHz,

DMSO-d₆): 20.5 (s, C-atom, CH₃of Acetyl group), 66.0 (s, C-6⁰⁰), 71.0 (s, C-4⁰⁰),

71.5 (s, C-3⁰⁰), 72.2 (s, C-2⁰⁰), 75.5 (s, C-5⁰⁰), 102.8 (s, C-1⁰⁰, anomeric C-atom),

104.1 (s, C-8), 108.1 (s, C-6), 115.1 (s, C-10), 114.8 (s, C-9⁰), 115.8 (s, C-12⁰),

117.8 (s, C-3), 122.4 (s, C-13⁰), 124.5 (s, C-8⁰), 127.0 (s, C-4⁰, C-7⁰), 127.5

Synthesis of O-b-D-glucopyranosides

117

(s, C-5⁰, C-6⁰), 130.8 (s, C-5), 139.1 (s, C-10⁰), 141.2 (s, C-2⁰), 142.0 (s, C-11⁰),

158.0 (s, C-9), 159.0 (s, C-2), 164.7 (s, C-7), 170.5 (s, C-atoms of Acetyl C55O),

176.0 (s, C-4, C55O).

Anal. Calcd. for C₃₄H₃₀N₂O₁₂(659): C, 62.00; H, 4.59; N, 4.25. Found: C,

62.01; H, 4.58; N, 4.23.

2,3,4,6-Tetra-O-acetyl-7-O-b-D-glucopyranosyloxy-3-(1H-phenanthro

[9,10-d] imidazol-2-yl)-4H-chromen-4-one (3c)

Yield 87%; [a]²_D⁵¼ 25.2 (c 0.1, CH₃OH); IR (KBr): 2924 (NH), 2854 (gluco-

sidic CH), 2363 (Ar-CH), 1757 (C55O of O-acetyl gps of glycone moiety), 1746

(C55O), 1590 (C55N), 1091 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): 2.02,

1.94, 1.96, 2.01 (s, 3H) (COCH₃), 3.81–4.25 (2H, m, 6⁰⁰-H), 4.45 (1H, dd,

5⁰⁰-H), 4.79 (1H, d, 1⁰⁰-H, anomeric proton), 4.84–4.99 (3H, m, 2⁰⁰,3⁰⁰,4⁰⁰-H),

6.38–8.98 (m, 11H, Ar-H), 7.57 (s, 2-H, CH), 11.7 (s, 1⁰-H, NH); ¹³C

NMR(100 MHz, DMSO-d₆): 22.5 (s, C-atom, CH₃of Acetyl group), 66.1

(s, C-6⁰⁰), 71.5 (s, C-4⁰⁰), 71.7 (s, C-3⁰⁰), 72.1 (s, C-2⁰⁰), 75.4 (s, C-5⁰⁰), 101.9

(s, C-1⁰⁰, anomeric C-atom), 104.1 (s, C-8), 109.4 (s, C-6), 114.8 (s, C-10), 117.8

(s, C-3), 122.8 (s, C-7⁰, C-8⁰), 127.2 (s, C-5⁰, C-6⁰, C-9⁰, C-10⁰), 127.9 (s, C-13⁰,

C-14⁰), 128.0 (s, C-12⁰, C-15⁰), 128.6 (s, C-4⁰, C-11⁰), 131.8 (s, C-16⁰, C-17⁰),

131.5 (s, C-5), 141.1 (s, C-2⁰), 158.0 (s, C-9), 158.9 (s, C-2), 163.8 (s, C-7),

169.9 (s, C-atoms of Acetyl C55O), 176.2 (s, C-4, C55O).

Anal. Calcd. for C₃₈H₃₂N₂O₁₂(708): C, 64.40; H, 4.55; N, 3.95. Found: C,

64.38; H, 4.54; N, 3.93.

3-(3,4,-Dihydroimidazo[4, 5-b]indol-2-yl)-2,3,4,6-tetra-O-acetyl-7-O-b-D-

glucopyranosyloxy-4H-chromen-4-one (3d)

Yield 85%; [a]²_D⁵¼ 28.1(c 0.1, CH₃OH); IR (KBr): 2945 (NH), 2855 (glucosi-

dic CH), 2365 (Ar-CH), 1754 (C55O of O-acetyl gps of glycone moiety), 1722

(C55O), 1646 (C55N), 1055 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 2.02,

1.91, 1.99, 2.00 (s, 3H, OAc), 3.89–4.29 (2H, m, 6⁰⁰-H), 4.41 (1H, dd, 5⁰⁰-H),

4.79 (1H, d, 1⁰⁰-H, anomeric proton), 4.86–5.02 (3H, m, 2⁰⁰,3⁰⁰,4⁰⁰-H), 6.33–7.59

(m, 7H, Ar-H), 7.60 (s, 2-H, CH), 10.7 (s, 8⁰-H, NH), 11.8 (s, 1⁰-H, NH); ¹³C

NMR (100 MHz, DMSO-d₆): 20.7 (s, C-atom, CH₃of Acetyl group), 66.1

(s, C-6⁰⁰), 71.2 (s, C-3⁰⁰), 71.3 (s, C-4⁰⁰), 72.1 (s, C-2⁰⁰), 75.4 (s, C-5⁰⁰), 102.9

(s, C-1⁰⁰, anomeric C-atom), 104.3 (s, C-8), 109.9 (s, C-6), 110.2 (s, C-7⁰), 116.0

(s, C-10), 118.6 (s, C-3), 118.9 (s, C-4⁰), 120.4 (s, C-6⁰), 120.9 (s, C-11⁰), 122.7

(s, C-5⁰), 131.6 (s, C-5), 135.0 (s, C-12⁰), 135.7 (s, C-2⁰), 136.8 (s, C-10⁰), 143.1

(s, C-9⁰), 157.1 (s, C-9), 160.2 (s, C-2), 164.1 (s, C-7), 171.0 (s, C-atoms of

Acetyl C55O), 175.8 (s, C-4, C55O).

Anal. Calcd. for C₃₂H₂₉N₃O₁₂(648): C, 59.35; H, 4.51; N, 6.49. Found: C,

59.33; H, 4.49; N, 6.49.

V. N. Ingle et al.

118

3-(7-Bromo-3,4,-dihydroimidazo[4, 5-b]indol-2-yl)-2,3,4,6-tetra-O-

acetyl-7-O-b-D-glucopyranosyloxy-4H-chromen-4-one (3e)

Yield 78%; [a]²_D⁵¼ 24.6 (c 0.1, CH₃OH); IR (KBr): 2957 (NH), 2857 (gluco-

sidic CH), 2360 (Ar-CH), 1776 (C55O of O-acetyl gps of glycone moiety), 1718

(C55O), 1645 (C55N), 1091 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 2.01,

2.00, 1.97, 2.01 (s, 3H, OAc), 3.87–4.29 (m, 2H, 6⁰⁰-H), 4.41 (dd, 1H, 5⁰⁰-H),

4.78 (d, 1H, 1⁰⁰-H, anomeric proton), 4.84–5.05 (m, 3H, 2⁰⁰,3⁰⁰,4⁰⁰-H), 6.41–7.77

(m, 6H, Ar-H), 7.57 (s, 2-H, CH), 10.8 (s, 8⁰-H, NH), 11.3 (s, 1⁰-H, NH); ¹³C

NMR (100 MHz, DMSO-d₆): 21.4 (s, C-atom, CH₃of Acetyl group), 66.1

(s, C-6⁰⁰), 71.1 (s, C-4⁰⁰), 71.3 (s, C-3⁰⁰), 71.9 (s, C-2⁰⁰), 75.1 (s, C-5⁰⁰), 101.9

(s, C-1⁰⁰, anomeric C-atom), 103.1 (s, C-8), 109.7 (s, C-6), 113.5 (s, C-7⁰), 115.9

(s, C-10), 116.8 (s, C-5⁰), 118.9 (s, C-3), 121.4 (s, C-4⁰), 121.8 (s, C-6⁰), 122.0

(s, C-11⁰), 131.0 (s, C-5), 134.1 (s, C-12⁰), 135.7 (s, C-2⁰), 136.2 (s, C-10⁰), 142.8

(s, C-9⁰), 157.5 (s, C-9), 158.7 (s, C-2), 164.1 (s, C-7), 170.0 (s, C-atoms of

Acetyl C55O), 174.8 (s, C-4, C55O).

Anal. Calcd. for C₃₂H₂₈BrN₃O₁₂(726): C, 52.90; H, 3.88; N, 5.78. Found: C,

52.85; H, 3.85; N, 5.71.

2,3,4,6-Tetra-O-acetyl-7-O-b-D-glucopyranosyloxy-3-(7-nitro-3,4,-

dihydroimidazo[4,5-b]indol-2-yl)-4H-chromen-4-one (3f)

Yield 70%; [a]²_D⁵¼ 27.7 (c 0.1, CH₃OH); IR (KBr): 2935 (NH), 2859 (gluco-

sidic CH), 2363 (Ar-CH), 1768 (C55O of O-acetyl gps of glycone moiety), 1717

(C55O), 1631 (C55N), 1074 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 2.00,

2.01, 1.98, 2.04 (s, 3H, OAc), 3.84–4.20 (m, 2H, 6⁰⁰-H), 4.41 (dd, 1H, 5⁰⁰-H),

4.77 (d, 1H, 1⁰⁰-H, anomeric proton), 4.81–4.99 (3H, m, 2⁰⁰,3⁰⁰,4⁰⁰-H), 6.40–8.50

(m, 6H, Ar-H), 7.54 (s, 2-H, CH), 10.5 (s, 8⁰-H, NH), 12.0 (s, 1⁰-H, NH); ¹³C

NMR (100 MHz, DMSO-d₆): 21.4 (s, C-atom, CH₃of Acetyl group), 66.0

(s, C-6⁰⁰), 71.1 (s, C-4⁰⁰), 71.4 (s, C-3⁰⁰), 73.1 (s, C-2⁰⁰), 74.9 (s, C-5⁰⁰), 101.7

(s, C-1⁰⁰, anomeric C-atom), 103.4 (s, C-8), 109.8 (s, C-6), 111.7 (s, C-7⁰), 114.4

(s, C-6⁰), 115.0 (s, C-4⁰), 115.8 (s, C-10), 119.0 (s, C-3), 120.6 (s, C-11⁰), 131.6

(s, C-5), 135.7 (s, C-2⁰), 136.4 (s, C-10⁰), 141.0 (s, C-5⁰), 141.3 (s, C-12⁰), 142.0

(s, C-9⁰), 158.2 (s, C-9), 159.0 (s, C-2), 163.7 (s, C-7), 171.0 (s, C-atoms of

Acetyl C55O), 175.1 (s, C-4, C55O).

Anal. Calcd. for C₃₂H₂₈N₄O₁₄(693): C, 55.49; H, 4.07; N, 8.09. Found: C,

55.45; H, 4.06; N, 8.08.

General Procedure for the Preparation of 7-O-b-D-

Glucopyranosyloxy-3-([4,5-fused] imidazol-2-yl)-

4H-chromen-4-ones (4)

The mixture of 2, 3, 4, 6-tetra-O-acetyl-7-O-b-D-glucopyranosyloxy -3-([4,

5-fused] imidazol-2-yl)-4H-chromen-4-ones (0.109 mmol), dry methanol (2 mL),

Synthesis of O-b-D-glucopyranosides

119

and anhydrous zinc acetate (23 mg, 0.126 mmol) was reﬂuxed for 7 h. After cooled

down at rt, 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 the titled compound.

7-O-b-D-Glucopyranosyloxy-3-(4,5,6,7-tetrahydro-1H-benzo[d]imidazol-

2-yl)-4H-chromen-4-one (4a)

Yield 77%; [a]²_D⁵¼ 220.1(c 0.1, DMSO); IR (KBr): 3412 (br, OH peak of

carbohydrate residue), 2929 (NH), 2853 (glucosidic CH), 2363 (Ar-CH), 1599

(C55O), 1445 (C55N), 1089 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d 1.57

(m, 5⁰-2H, 6⁰-2H) (CH₂), 2.48 (t, 4⁰-2H, 7⁰-2H) (CH₂), 3.44–4.72 (m, 6H, b-D-glu-

copyranosyl ring), 5.74 (d, 1⁰⁰-H, anomeric proton), 6.36–7.49 (m, 3H, Ar-H),

7.50 (s, 2-H, CH), 11.2 (s, 1⁰-H, NH); ¹³C NMR (100 MHz, DMSO-d₆): 21.9

(s, C-5⁰, C-6⁰), 25.0 (s, C-4⁰, C-7⁰), 64.0 (s, C-6⁰⁰), 73.1 (s, C-4⁰⁰), 74.9 (s, C-2⁰⁰),

77.6 (s, C-3⁰⁰), 82.1 (s, C-5⁰⁰), 104.0 (s, C-8), 106.0 (s, C-1⁰⁰, anomeric C-atom),

109.9 (s, C-6), 116.2 (s, C-10), 118.2 (s, C-3), 124.6 (s, C-8⁰, C-9⁰), 130.8

(s, C-5), 135.4 (s, C-2⁰), 158.1 (s, C-9), 159.6 (s, C-2), 163.8 (s, C-7), 174.7

(s, C-4, C55O); MS (EI, 70 eV): m/z (%) 445 (10) [M þ 1]^þ, 282 (100), 163 (25),

161 (18), 91 (30).

Anal. Calcd. for C₂₂H₂₄N₂O₈(444): C, 59.45; H, 5.44; N, 6.30. Found: C,

59.44; H, 5.43; N, 6.31.

7-O-b-D-Glucopyranosyloxy-3-(3H-naphtho[2,1-d]imidazol-2-yl)-4H-

chromen-4-one (4b)

Yield 69%; [a]²_D⁵¼ 217.6 (c 0.1, DMSO); IR (KBr): 3446 (br, OH peak of

carbohydrate residue), 2958 (NH), 2856 (glucosidic CH), 2363 (Ar-CH), 1598

(C55O), 1414 (C55N), 1091 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d

3.45–4.95 (m, 6H, b-D-glucopyranosyl ring), 5.69 (d, 1⁰⁰-H, anomeric proton),

6.41–7.78 (m, 9H, Ar-H), 7.52 (s, 2-H, CH), 12.8 (s, 1⁰-H, N-H); ¹³C NMR

(100 MHz, DMSO-d₆): 65.8 (s, C-6⁰⁰), 73.0 (s, C-4⁰⁰), 75.9 (s, C-2⁰⁰), 77.7

(s, C-3⁰⁰), 81.1 (s, C-5⁰⁰), 103.5 (s, C-8), 105.0 (s, C-1⁰⁰, anomeric C-atom), 109.3

(s, C-6), 115.1 (s, C-10), 115.3 (s, C-9⁰), 115.9 (s, C-12⁰), 118.0 (s, C-3), 123.2

(s, C-13⁰), 124.2 (s, C-8⁰), 127.1 (s, C-5⁰, C-6⁰), 127.9 (s, C-4⁰, C-7⁰), 131.1

(s, C-5), 139.1 (s, C-10⁰), 141.2 (s, C-2⁰), 142.1 (s, C-11⁰), 158.1 (s, C-9), 159.6

(s, C-2), 163.5 (s, C-7), 176.0 (s, C-4, C55O); MS (EI, 70 eV): m/z (%) 491 (7)

[M þ 1]^þ, 328 (M^þ, 100), 163 (18), 161 (15), 91 (19).

Anal. Calcd. for C₂₆H₂₂N₂O₈(490): C, 63.67; H, 4.52; N, 5.71. Found: C,

63.65; H, 4.51; N, 5.88.

7-O-b-D-Glucopyranosyloxy-3-(1H-phenanthro[9,10-d]imidazol-2-yl)-

4H-chromen-4-one (4c)

Yield 94%; [a]²_D⁵¼ 213.7 (c 0.1, DMSO); IR (KBr): 3400 (br, OH peak of

carbohydrate residue), 2925 (NH), 2854 (glucosidic CH), 2363 (Ar-CH), 1592

V. N. Ingle et al.

120

(C55O), 1404 (C55N), 1071 (C-O-C); H NMR (400 MHz, DMSO-d₆): d 3.41–

4.70 (m, 6H, b-D-glucopyranosyl ring), 5.85 (d, 1⁰⁰-H, anomeric proton), 6.40–

8.90 (m, 11H, Ar-H), 7.49 (s, 2-H, CH), 12.0 (s, 1⁰-H, NH); ¹³C NMR

(100 MHz, DMSO-d₆): 65.7 (s, C-6⁰⁰), 73.9 (s, C-4⁰⁰), 75.1 (s, C-2⁰⁰), 77.0

(s, C-3⁰⁰), 81.2 (s, C-5⁰⁰), 103.1 (s, C-8), 105.4 (s, C-1⁰⁰, anomeric C-atom), 109.1

(s, C-6), 114.9 (s, C-10), 119.4 (s, C-3), 122.0 (s, C-7⁰, C-8⁰), 126.1 (s, C-5⁰, C-6⁰,

C-9⁰, C-10⁰), 126.8 (s, C-13⁰, C-14⁰), 127.9 (s, C-12⁰, C-15⁰), 128.4 (s, C-4⁰,

C-11⁰), 131.0 (s, C-5), 131.1 (s, C-16⁰, C-17⁰), 142.1 (s, C-2⁰), 157.7 (s, C-9),

159.1 (s, C-2), 164.7 (s, C-7), 176.2 (s, C-4, C55O); MS (EI, 70 eV): m/z (%)

541 (13) [M þ 1]^þ, 378 (100), 217 (13), 163 (40), 161 (20), 91 (11).

Anal. Calcd. for C₃₀H₂₄N₂O₈(540): C, 66.66; H, 4.48; N, 5.18. Found: C,

66.65; H, 4.47; N, 5.16.

3-(3,4,-Dihydroimidazo[4,5-b]indol-2-yl)-7-O-b-D-glucopyranosyloxy-

4H-chromen-4-one (4d)

Yield 80%; [a]²_D⁵¼ 215.3 (c 0.1, DMSO); IR (KBr): 3428 (br, OH peak of

carbohydrate residue), 2929 (NH), 2858 (glucosidic CH), 2363 (Ar-CH), 1597

(C55O), 1429 (C55N), 1100 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d

3.43–4.78 (m, 6H, b-D-glucopyranosyl ring), 5.80 (d, 1⁰⁰-H, anomeric proton),

6.33–7.58 (m, 7H, Ar-H), 7.48 (s, 2-H, CH), 9.9 (s, 8⁰-H, NH), 11.8 (s, 1⁰-H,

NH); C NMR (100 MHz, DMSO-d₆): 64.9 (s, C-6⁰⁰), 73.9 (s, C-4⁰⁰), 75.2

(s, C-2⁰⁰), 77.2 (s, C-3⁰⁰), 81.4 (s, C-5⁰⁰), 104.1 (s, C-8), 106.2 (s, C-1⁰⁰, anomeric

C-atom), 109.5 (s, C-6), 111.5 (s, C-7⁰), 115.1 (s, C-10), 118.9 (s, C-3), 119.7

(s, C-4⁰), 120.3 (s, C-6⁰), 120.6 (s, C-11⁰), 122.9 (s, C-5⁰), 130.9 (s, C-5), 135.1

(s, C-12⁰), 135.8 (s, C-2⁰), 136.6 (s, C-10⁰), 143.1 (s, C-9⁰), 157.1 (s, C-9), 160.2

(s, C-2), 164.5 (s, C-7), 176.1 (s, C-4, C55O); MS (EI, 70 eV): m/z (%) 480(9)

[M]^þ, 317 (100), 163 (41), 161 (15), 91 (34).

Anal. Calcd. for C₂₄H₂₁N₃O₈(480): C, 60.12; H, 4.41; N, 8.76. Found: C,

60.10; H, 4.27; N, 8.67.

3-(7-Bromo-3,4,-dihydroimidazo[4,5-b]indol-2-yl)-7-O-b-D-

glucopyranosyloxy-4H-chromen-4-one (4e)

Yield 81%; [a]²_D⁵¼ 214.5 (c 0.1, DMSO); IR (KBr): 3411(br, OH peak of

carbohydrate residue), 2944 (NH), 2855 (glucosidic CH), 2365 (Ar-CH), 1593

(C55O), 1415 (C55N), 1099 (C-O-C); ¹H NMR (400 MHz, DMSO-d₆): d

3.45–4.78 (m, 6H, b-D-glucopyranosyl ring), 5.54 (d, 1⁰⁰-H, anomeric proton),

6.37–7.79 (m, 6H, Ar-H), 7.54 (s, 2-H, CH), 10.6 (s, 8⁰-H, NH), 11.5 (s, 1⁰-H,

NH); C NMR (100 MHz, DMSO-d₆): 64.6 (s, C-6⁰⁰), 73.1 (s, C-4⁰⁰), 74.7

(s, C-2⁰⁰), 78.1 (s, C-3⁰⁰), 81.1 (s, C-5⁰⁰), 103.5 (s, C-8), 106.1 (s, C-1⁰⁰, anomeric

C-atom), 110.1 (s, C-6), 113.0 (s, C-7⁰), 115.3 (s, C-10), 117.4 (s, C-5⁰), 118.1

(s, C-3), 120.7 (s, C-4⁰), 121.0 (s, C-6⁰), 121.8 (s, C-11⁰), 131.4 (s, C-5), 134.0

(s, C-12⁰), 135.6 (s, C-2⁰), 136.8 (s, C-10⁰), 142.0 (s, C-9⁰), 157.4 (s, C-9), 158.8

(s, C-2), 163.8 (s, C-7), 176.1 (s, C-4, C55O).

Synthesis of O-b-D-glucopyranosides

121

Anal. Calcd. for C₂₄H₂₀BrN₃O₈(558): C, 51.63; H, 3.61; N, 7.53. Found: C,

51.64; H, 3.60; N, 7.52.

7-O-b-D-Glucopyranosyloxy-3-(7-nitro-3,4,-dihydroimidazo[4,5-b] indol-

2-yl)-4H-chromen-4-one (4f)

Yield 75%; [a]²_D⁵¼ 218.4 (c 0.1, DMSO); IR (KBr): 3454 (br, OH peak of

carbohydrate residue), 2928 (NH), 2852 (glucosidic CH), 2365 (Ar-CH),

1591 (C55O), 1420 (C55N), 1095 (C-O-C); H NMR (400 MHz, DMSO-d₆): d

3.41–4.74 (m, 6H, b-D-glucopyranosyl ring), 5.68 (d, 1⁰⁰-H, anomeric proton),

6.38–8.52 (m, 6H, Ar-H), 7.59 (s, 2-H, CH), 10.0 (s, 8⁰-H, NH), 11.3 (s, 1⁰-H,

NH); C NMR (100 MHz, DMSO-d₆): 64.1 (s, C-6⁰⁰), 73.1 (s, C-4⁰⁰), 75.8

(s, C-2⁰⁰), 77.2 (s, C-3⁰⁰), 82.4 (s, C-5⁰⁰), 104.3 (s, C-8), 106.2 (s, C-1⁰⁰, anomeric

C-atom), 109.9 (s, C-6), 111.8 (s, C-7⁰), 114.9 (s, C-6⁰), 115.1 (s, C-10), 116.1

(s, C-4⁰), 117.8 (s, C-3), 120.8 (s, C-11⁰), 130.9 (s, C-5), 135.7 (s, C-2⁰), 136.8

(s, C-10⁰), 142.2 (s, C-5⁰), 142.3 (s, C-12⁰), 142.9 (s, C-9⁰), 158.2 (s, C-9), 159.0

(s, C-2), 165.1 (s, C-7), 176.1 (s, C-4, C55O).

Anal. Calcd. for C₂₄H₂₀N₄O₁₀(524): C, 54.97; H, 3.84; N, 10.68. Found: C,

54.95; H, 3.80; N, 10.67.

BIOLOGICAL ASSAYS

Antibacterial Assays

The synthesized compounds 4a–f were screened for their in vitro antibac-

terial activity against E. coli, K. aerogens, S. aureus, and B. substilis by the cup

plate diffusion method. The test compounds were dissolved in methanol at a

concentration of 100mg/mL by using standard ciproﬂoxacin and sulphaceta-

mide (100mg/ml) for bacteria. The zone of inhibition after 24 h of incubation

at 378C was compared with standard drugs.

Antifungal Assays

Compounds 4a–f were also screened at 100mg/ml concentration in

methanol against A. niger and C. albicans for their antifungal activity by

the cup plate diffusion method. The zone of inhibition after 7 days at

208C was compared with standard drugs gentamycin and clotrimazole

(100 mg/mL).

Antioxidant Assays

In vitro free radical scavenging activities of 4a–f were evaluated by DPPH

assay method. This method is based on the reduction of a methanolic solution of

V. N. Ingle et al.

122

the colored DPPH radical. To a set of test tubes containing 3 mL of methanol,

50 mL of DPPH reagent (2 mg/mL) was added. The initial absorbance was

measured. To this test tube, methanolic solution of different test solutions

(1 mg/mL) were added (10–50 mL). Ascorbic acid (0.5 mg/mL) was added in

the range of 10–25mL. After 20 min, absorbance was recorded at 516 nm.

The experiment was performed in triplicate. The percentage reduction in

absorbance was calculated from the initial and ﬁnal absorbance of each

solution. Percentage scavenging of DPPH radical was calculated using the

formula:

% Scavenging of DPPH ¼ ½ðControl ꢁ TestÞ=Controlꢂ ꢀ 100

ACKNOWLEDGMENTS

The authors are sincerely thankful to the Director, SAIF, Chandigarh, and the

Head, Department of Chemistry, IIT-Pawai, Mumbai, for providing spectral

data of the compounds; Head, Department of Pharmaceutical Sciences, R T M

Nagpur University, Nagpur, for biological activity; and Head, Department

of Chemistry, R T M Nagpur University, Nagpur, for providing necessary

laboratory facilities.

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