CC BY
9Heterocycles
Гетероциклы
Макрогэтэроцмклы
Статья
Paper
http://macroheterocycles.isuct.ru
DOI: 10.6060/mhc121091h
Synthesis and Biological Study of O—ß—D—Glucosides of 7-Hydroxy-3-(Disubstituted Imidazol—2—yl)—4H—chromen—4—ones
Kishor M. Hatzade,ab@ Vijay S. Taile,a and Vishwas N. Inglea
aDepartment of Chemistry, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur-440033, India hDepartment of Chemistry, Dhote Bandhu Science College, Gondia-441614, India @Corresponding author E-mail: [email protected]
A series of 7-o-fi-D-glucopyranosyloxy-3-(disubstituted imidazol-2-yl)-4H-chromen-4-ones 5 was synthesized. The 7-hydroxy-3-formyl-4H-chromen-4-one 1 reacted with various 1,2-dicarbonyl compounds 2 in the presence of ammonium acetate to furnish 7-hydroxy-3-(4,5-disubstitutedimidazol-2-yl)-4H-chromen-4-ones 3, which on glucosylation with a-acetobromoglucose affords 2,3,4,6-tetra-o-acetyl-7-o-fi-D-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones 4. 7-o-fi-D-Glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones 5 were prepared by deacetylation with anhydrous zinc acetate in absolute methanol. Elemental analysis, IR, 1H NMR, 13C NMR, EI-MS spectral data were obtained to determine the structure of the newly synthesized compounds.
Keywords: Chromone, imidazole, acetobromoglucose, glucosylation, glucosides.
3Rashtrasant Tukadoji Maharaj Nagpur University, 440033 Нагпур, Индия bDhote Bandhu Science College, 441614 Гондия, Индия @E-mail: [email protected]
Была синтезирована серия 0-ß-D-глюкопиранозилкоси-7-гидрокси-4Н-хромен-4-онов с 4',5'-дизамещенными 3-имидазол-2'-ильными фрагментами 5. 7-Гидрокси-3-формил-4Н-хромен-4-он 1 взаимодействовал с 1,2-дикарбонил замещенными соединениями 2 в присутствии ацетата аммония с образованием 7-гидрокси-4Н-хромен-4-онов с 4',5'-дизамещенными 3-имидазол-2'-ильными фрагментами 4. O-ß-D-глюкопиранозилкоси-7-гидрокси-4Н-хромен-4-оны с 4',5'-дизамещенными 3-имидазол-2'-ильными фрагментами 5 были получены деацилированием с безводным ацетатом цинка в абсолютном метаноле. Новые соединения были охарактеризованы с помощью элементного анализа, ИК, H и 13C ЯМР спектроскопии и масс-спектрометрии
Синтез и биологические исследования O—ß—D—гликозидов 7—гидрокси—4Н—хромен—4—онов с 4\5'—дизамещенными 3—имидазол—2'—ильными фрагментами
К. М. Хатзаде,^ В. С. Таиле^ В. Н. Ингле
»a
(EI-MS).
Ключевые слова: Хромоны. имидазол, ацетобромоглюкоза, глюкозилирование, гликозиды.
Introduction
Carbohydrates are being considered as extremely useful stereo chemical building blocks for complex organic synthesis.111 Apart from being an energy source in leaving systems, carbohydrates increasingly are being recognized as playing important roles in a variety of biological processes, such as signaling, cell-cell communications, molecular and cellular targeting.121 o-j#-D-Glucosides possess higher degree of biological activities such as cell growth regulation, cell differentiation, immunological response, antitumour, antiparasitic, antifungal activities.13-111 Several therapeutically interesting biological activities of certain flavonoids have been reported including anticancer,112-171 anti-HIV,[18-20] and antioxidant121-231 properties. Similarly imidazoles show antimalerial, antituberculosis, antifungal, anticonvulsant, antiprotozoal, anticancer, antihypertensive, anorectic, hypoglysacemic activities.[24] Considering the above facts and also in continuation of our studies[25] on chromone based heterocycles promoted to prepare several new organic compounds containing chromone, imidazole and glucose moieties. Herein we report the synthesis of new substituted flavonoids 7-hydroxy-3-(imidazol-2-yl)-chromones 3. These compounds were glucosylated with a-acetobromoglucose yielding 7-o-#-D-glucopyranosyloxy-3-(imidazol-2-yl)-chromones 5.
C-9), 135.9 (s, C-5'), 131.9 (s, C-5), 128.0 (s, C-2',C-3'), 118.2 (s, C-3), 115.8 (s, C-10), 111.0 (s, C-6), 104.6 (s, C-8). EI-MS m/z (%): 229 (M+, 100), 136 (18), 91 (30). Anal. Calcd for C12H8N2O3: C, 63.16; H, 3.53; N, 12.28. Found: C, 63.10; H, 3.51; N, 12.21(%).
7-Hydroxy-3-(4,5-dimethylimidazol-2-yl)-chromone 3b. Yield 76 %, mp 295 oC (chloroform + dioxane). IR (KBr) v cm-1: 3412 (OH), 2989 (N-H), 1609 (C=O), 1452 (C=N), 1166 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 13.1 (s, 1'-H, N-H), 7.52 (s, 2-H, CH), 6.45-7.50 (m, 3H, Ar-H), 4.99 (s, 1H, -OH), 2.31(s, 2'-H, CH3), 2.20 (s, 3'-H, CH3); 13C NMR (DMSO-d6) 5C ppm: 176.1 (s, C-4, C=O), 164.5 (s, C-7), 158.9 (s, C-2), 157.8! (s, C-9), 135.7 (s, C-5'), 132.1 (s, C-2', C-3'), 131.4 (s, C-5), 119.0 (s, C-3), 116.8 (s, C-10), 110.1 (s, C-6), 105.5 (s, C-8), 12.2 (s, CH3 of C-2', C-3'). EI-MS m/z (%): 257 (M+, 100), 136 (15), 91 (19). Anal. Calcd for C14H12N2O3: C, 65.62; H, 4.72; N, 10.93. Found: C, 65.58; H, 4.72; N, 10.89(%).
7-Hydroxy-3-(4-phenylimidazol-2-yl)-chromone 3c. Yield 78 %, mp 282 oC (ethanol). IR (KBr) v cm-1: 3400 (OH), 2990 (N-H), 1622 (C=O), 1455 (C=N), 1171 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.7 (s, 1'-H, N-H), 7.56 (s, 2-H, CH), 7.05 (s, 2'-H, C H), 6.41-7.50 (m, 8H, Ar-H), 5.02 (s, 1H, -OH). 13C NMR (DMSO-d6) 5C ppm: 174.8 (s, C-4, C=O), 165.1 (s, C-7), 160.0 (s, C-2), 157.5 (s, C-9), 140.1 (s, C-3'), 135.5 (s, C-5'), 132.0 (s, C-5), 125-133.5 (aromatic 6C-atom), 121.0 (s, C-2'), 117.6 (s, C-3), 115.9 (s, C-10), 110.1 (s, C-6), 104.8 (s, C-8). EI-MS m/z (%): 305 (M+, 100), 136 (10), 91 (21). Anal. Calcd for C18H12N2O3: C, 71.05; H, 3.97; N, 9.21. Found: C, 71.01; H, 3.93; N, 9.21(%).
7-Hydroxy-3-(4,5-diphenylimidazol-2-yl)-chromone 3d. Yield 90 %, mp 220 oC (chloroform + dioxane). IR (KBr) v cm-1: 3412
HO.
O
HO
O
3a-i
HOH
5a-i
O
Experimental
All melting points (mp) measured in open capillary tube were uncorrected. FT-IR spectra were recorded on Perkin-Elmer spectrum Rx-I spectrophotometer. 1H and 13C NMR spectra were recorded on a Bruker II-400 NMR spectrophotometer (1H, 400 MHz and 13C, 100 MHz), using TMS as an internal standard in DMSO and CDCl3. Chemical shifts are reported (5) relative to TMS. Mass spectra were determined on Hitachi Perkin-Elmer RMU 6D mass spectrometer. Elemental analysis for C, H, and N were determined using the Perkin-Elmer 2400 CHN rapid analyzer. Chemicals were obtained from Merck and Fluka and used without further purification. Various 1,2-dicarbonyl compounds were prepared using methods described in literature.[27]
General procedure for the synthesis of compounds 3a-i. A mixture of 7-hydroxy-3-formyl chromone 1 (5 mmol), 1,2-dicarbonyl compounds 2a-i (5 mmol), ammonium acetate (10 mmol) and glacial acetic acid (50 ml) was refluxed for 2-3 h (monitored by TLC). It was poured on to cold water (200 ml). The solid obtained was filtered, washed with water and crystallized from solvents.
7-Hydroxy-3-(imidazol-2-yl)-chromone 3a. Yield 81 %, mp 290 oC (ethanol). IR (KBr) v cm-1: 3451 (OH), 2958 (N-H), 1616 (C=O), 1455 (C=N), 1150 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 12.9 (s, 1'-H, N-H), 7.26 (s, 2-H, CH), 7.05 (d, 2'-H, 36-H) (CH), 6.40-7.49 (m, 3H, Ar-H), 5.12 (s, 1H, -OH). 13C NMR (DMSO-d6) 5C ppm: 174.9 (s, C-4, C=O), 163.9 (s, C-7), 159.8 (s, C-2), 159.0 (s,
(OH), 2992 (N-H), 1631 (C=O), 1456 (C=N), 1160 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 12.9 (s, 1'-H, N-H), 7.57 (s, 2-H, CH), 6.43-7.50 (m, 13H, Ar-H), 4.94 (s, 1H, -OH). 13C NMR (DMSO-d6) 5C ppm: 175.2 (s, C-4, C=O), 164.9 (s, C-7), 159.4 (s, C-2), 157.9 (s, C-9), 135.6 (s, C-5'), 133.1 (s, C-5), 129.0 (s, C-2', C-3'), 127133 (aromatic 12C-atom), 117.9 (s, C-3), 117.0 (s, C-10), 109.8 (s, C-6), 106.1 (s, C-8). EI-MS m/z (%): 380 (M+, 100), 136 (15), 91 (34). Anal. Calcd for C H, NO: C, 75.78; H, 4.24; N, 7.36.
24 16 2 3
Found: C, 75.75; H, 4.21; N, 7.35(%).
7-Hydroxy-3-[4-phenyl,5-(p-methoxyphenyl)imidazol-2-yl]-chromone 3e Yield 89 %, mp 284 oC (chloroform + dioxane). IR (KBr) v cm-1: 3447 (OH), 2994 (N-H), 1620 (C=O), 1457 (C=N), 1154 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 12.6 (s, 1'-H, N-H), 7.52 (s, 2-H, CH), 6.38-7.49 (m, 12H, Ar-H), 4.93 (s, 1H, -OH), 3.69 (s, 3H, OCH3). 13C NMR (DMSO-d6) 5C ppm: 176.1 (s, C-4, C=O), 165.2 (s, C-7), 159.0 (s, C-9), 158.9 (s, C-2), 136.1 (s, C-5'), 131.6 (s, C-5), 128.7 (s, C-2', C-3'), 119.2 (s, C-3), 117.1 (s, C-10), 115-135 (aromatic 12C-atom), 109.8 (s, C-6), 106.1 (s, C-8), 54.8 (s, C-atom of OCH3). EI-MS m/z (%): 411 (M+, 100), 136 (17), 91 (10). Anal. Calcd for C18H12N2O3: C, 73.16; H, 4.42; N, 6.83. Found: C, 73.11; H, 4.39; N, 6.80(%).
7-Hydroxy-3-[4,5-di(o-chlorophenyl)imidazol-2-yl]-chromone 3f. Yield 78 %, mp 231 oC (ethanol), IR (KBr) v cm-1: 3443 (OH), 2999 (N-H), 1624 (C=O), 1452 (C=N), 1166 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 11.9 (s, 1'-H, N-H), 7.52 (s, 2-H, CH),
H
H
1
6.41-7.45 (m, 11H, Ar-H), 4.96 (s, 1H, -OH). 13C NMR (DMSO-d6) 5C ppm: 176.1 (s, C-4, C=O), 164.7 (s, C-7), 159.9 (s, C-2), 159.1 (s, C-9), 136.7 (s, C-5'), 132.0 (s, C-5), 129.9 (s, C-2', C-3'), 125.0135.1 (aromatic 12C-atom), 118.1 (s, C-3), 117.2 (s, C-10), 109.9 (s, C-6), 104.6 (s, C-8). EI-MS m/z (%): 450 (M+, 100), 136 (25), 91 (26). Anal. Calcd for CHNO: C, 64.16; H, 3.14; N, 6.24.
v/ 24 1623' 77 77
Found: C, 64.12; H, 3.11; N, 6.22(%).
7-Hydroxy-3-[4,5-di(p-chlorophenyl)imidazol-2-yl]-chromone 3g. Yield 83 %, mp 280 oC (ethanol). IR (KBr) v cm-1: 3449 (OH), 2994 (N-H), 1629 (C=O), 1465 (C=N), 1054 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.2 (s, 1'-H, N-H), 7.43 (s, 2-H, CH), 6.35-7.40 (m, 11H, Ar-H), 4.90 (s, 1H, -OH). 13C NMR (DMSO-d6) SC ppm: 176.9 (s, C-4, C=O), 164.1 (s, C-7), 160.1 (s, C-2), 159.6 (s, C-9), 137.0 (s, C-5'), 132.7 (s, C-5), 130.1 (s, C-2', C-3'), 124.6135.5 (aromatic 12C-atom), 118.6 (s, C-3), 117.8 (s, C-10), 109.1 (s, C-6), 104.9 (s, C-8). EI-MS m/z (%): 450 (M+, 100), 136 (29), 91 (36). Anal. Calcd for CHNO: C, 64.16; H, 3.14; N, 6.24.
24 16 2 3
Found: C, 64.10; H, 3.04; N, 6.16(%).
7-Hydroxy-3-[4,5-di(p-N,N-dimethylaminophenyl)imidazol-2-yl]-chromone 3h. Yield 73 %, mp 278 oC (chloroform + dioxane). IR (KBr) v cm-1: 3433 (OH), 2989 (N-H), 1639 (C=O), 1443 (C=N), 1123 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.8 (s, 1'-H, N-H), 7.23 (s, 2-H, CH), 6.51-7.49 (m, 11H, Ar-H), 4.96 (s, 1H, -OH), 2.88 (s, 6H, N(CH3)2), 2.79 (s, 6H, N(CH3)2). 13C NMR (DMSO-d6) SC ppm: 176.2 (s, C-4, C=O), 164.5 (s, C-7), 160.7 (s, C-2), 160.1 (s, C-9), 137.5 (s, C-5'), 132.1 (s, C-5), 130.7 (s, C-2', C-3'), 124.0136.1 (aromatic 12C-atom), 118.2 (s, C-3), 117.1 (s, C-10), 109.8 (s, C-6), 105.2 (s, C-8), 40.1 (s, N(CH3)2), 40.7 (s, N(CH3)2). Anal. Calcd for C28H26N4O3: C, 72.09; H, 5.02; N, 12.01. Found: C, 72.01; H, 4.96; N, 11.92(%).
7-Hydroxy-3-[4,5-di(p-methylphenyl)imidazol-2-yl]-chromone 3i. Yield 82 %, mp 290 oC (chloroform + dioxane). IR (KBr) v cm-1: 3441 (OH), 2988 (N-H), 1652 (C=O), 1439 (C=N), 1099 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.6 (s, 1'-H, N-H), 7.36 (s, 2-H, CH), 6.29-7.49 (m, 11H, Ar-H), 4.92 (s, 1H, -OH), 2.29 (s, 3H, CH3), 2.25 (s, 3H, CH3); 13C NMR (DMSO-d6) 5C ppm: 175.3 (s, C-4, C=O), 164.0 (s, C-7), 160.4 (s, C-2), 159.1 (s, C-9), 137.6 (s, C-5'), 132.2 (s, C-5), 130.4 (s, C-2', C-3'), 119.7-135.9 (aromatic 12C-atom), 118.2 (s, C-3), 117.1 (s, C-10), 109.8 (s, C-6), 104.1 (s, C-8), 24.0 (s, C-atom of CH3), 23.7 (s, C-atom of CH3). Anal. Calcd for C,,HnN,O ■ C, 76.45; H, 4.94; N, 6.86. Found: C,
26 20 2 3
76.36; H, 4.85; N, 6.77(%).
General procedure for the synthesis of compounds 4a-i. In a 250 ml round-bottomed flask, anhydrous K2CO3 (6.3 mmol) was added to the mixture of dry DMF (9 ml) and acetone (6 ml), then 7-hydroxy-3-(4,5-disubstituted imidazol-2-yl)-chromones 3a-i (0.30 mmol), DTMAB (10 mg) and a-acetobromoglucose (0.60 mmol) were added under stirring, the reaction mixture was refluxed for 5-6 h (monitored by TLC). Then acetone was removed under vacuum, water (20 ml) was added to the flask. The mixture was extracted with ethyl acetate (5x10 ml), the organic layer was washed by 20 ml water and brine, dried over anhydrous MgSO4, then removed the solvent to give the residue which was purified by silica gel flash chromatography (ethyl acetate: petroleum ether 1:2 v/v) to give a brown coloured semisolid.
7-(2,3,4,6-Tetra-o-acetyl-o-b-D-glucopyranosyloxy)-3-(imidazol-2-yl)-chromone 4a. Yield 86 %, [a]D25 = - 3.1 (c 0.1, CH3OH). IR (KBr) v cm-1: 2954 (N-H), 2854 (glucosidic-CH), 1761 (C=O of O-acetyl gps of glycone moiety), 1722 (C=O), 1646 (C=N), 1052 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.5 (s, 1'-H, N-H), 7.46 (s, 2-H, CH), 7.15 (d, 2'-H, 3'-H) (CH), 6.44-7.43 (m, 3H, Ar-H), 4.87-5.00 (m, 3H, 2", 3", 4"-H), 4.76 (d, 1H, 1"-H, anomeric proton), 4.39 (dd, 1H, 5"-H), 3.86-4.24 (m, 2H, 6"-H), 2.01, 1.95, 1.99, 2.05 (s, 3H, OAc). 13C NMR (DMSO-d6) SC ppm: 174.9 (C-4, C=O), 171.0 (C-atoms of acetyl C=O), 164.2 (C-7), 159.1 (C-2), 158.1 (C-9), 135.9 (C-5'), 130.9 (C-5), 128.0 (C-2',
C-3'), 117.6 (C-3), 116.2 (C-10), 110.1 (C-6), 103.4 (C-8), 101.9 (C-1", anomeric C-atom), 74.9 (C-5"), 72.8 (C-2"), 71.5 (C-4"), 71.1 (C-3"), 66.1 (C-6"), 21.8 (C-atom, CH3 of acetyl group). EI-MS m/z (%): 559 (M+, 17), 228 (100), 136 (12), 91 (25). Anal. Calcd for C26H28O12N2: C, 55.91; H, 4.69; N, 5.02. Found: C, 55.89; H, 4.66; N, 5.00(%).
7-(2,3,4,6-Tetra-o-acetyl-o-^-D-glucopyranosyloxy)-3-(4,5-dimethylimidazol-2-yl)-chromone 4b. Yield 76 %, [a]D25 = - 5.1 (c 0.1, CH3OH). IR (KBr) v cm-1: 2935.1 (N-H), 2882 (glucosidic-CH), 1758 (C=O of o-acetyl gps of glycone moiety), 1727 (C=O), 1624 (C=N), 1055 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.9 (s, 1'-H, N-H), 7.48 (s, 2-H, CH), 6.49-7.49 (m, 3H, Ar-H), 4.855.04 (m, 3H, 2", 3", 4"-H), 4.71 (d, 1H, 1"-H, anomeric proton), 4.40 (dd, 1H, 5"-H), 3.90-4.21 (m, 2H, 6"-H), 2.34 (s, 2'-H, CH3), 2.24 (s, 3'-H, CH3), 2.02, 1.96, 1.98, 2.04 (s, 3H, OAc). 13C NMR (DMSO-d6) 5C ppm: 176.0 (C-4, C=O), 170.5 (C-atoms of acetyl C=O), 1646.7 (C-7), 159.0 (C-2), 158.0 (C-9), 135.7 (C-5'), 132.1 (C-2', C-3'), 130.8 (C-5), 117.8 (C-3), 115.1 (C-10), 108.1 (C-6), 104.1 (C-8), 102.8 (C-1", anomeric C-atom), 75.5 (C-5"), 72.2 (C-2"), 71.5 (C-3"), 71.0 (C-4"), 66.0 (C-6"), 20.9 (C-atom, CH3 of acetyl group), 11.4 (CH3 of C-2', C-3'); EI-MS m/z (%): 587 (M+, 11), 256 (100), 136 (21), 91 (25). Anal. Calcd for C28H32N2O12: C, 57.34; H, 5.16; N, 4.78. Found: C, 57.31; H, 5.16; N, 4.75(%).
7-(2,3,4,6-Tetra-o-acetyl-o-^-D-glucopyranosyloxy)-3-(4-phenylimidazol-2-yl)-chromone 4c. Yield 88 %, [a]D25 = - 1.5 (c 0.1, CH3OH). IR (KBr) v cm-1: 2924 (N-H), 2854 (glucosidic-CH), 1758 (C=O of o-acetyl gps of glycone moiety), 1729 (C=O), 1621 (C=N), 1037 (C-O-C), 689 (benzene monosubstituted). 1H NMR (DMSO-d6) SH ppm: 12.5 (s, 1'-H, NH), 7.50 (s, 2-H, CH), 7.09 (s, 2'-H, CH), 6.41-7.60 (m, 8H, Ar-H), 4.84-4.99 (m, 3H, 2", 3", 4"-H), 4.79 (1H, d, 1"-H, anomeric proton), 4.45 (1H, dd, 5"-H), 3.81-4.25 (m, 2H, 6"-H), 2.02, 1.94, 1.96, 2.01 (s, 3H, OAc). 13C NMR (DMSO-d6) SC ppm: 176.2 (C-4, C=O), 169.9 (C-atoms of acetyl C=O), 163.8 (C-7), 158.9 (C-2), 158.0 (C-9), 139.9 (C-3'), 135.5 (C-5'), 127.5-133.5 (aromatic 6C-atom), 131.5 (C-5), 119.9 (C-2'), 117.8 (C-3), 114.8 (C-10), 109.4 (C-6), 104.1 (C-8), 101.9 (C-1", anomeric C-atom), 75.4 (C-5"), 72.1 (C-2"), 71.7 (C-3"), 71.5 (C-4"), 66.1 (C-6"), 22.0 (C-atom, CH3 of acetyl group). EI-MS m/z (%): 634 (M+, 20), 304 (100), 136 (16), 91 (29). Anal. Calcd for C32H32O12N2: C, 60.57; H, 4.77; N, 4.41. Found: C, 60.54; H, 4.76; N, 4.36(%).
7-(2,3,4,6-Tetra-o-acetyl-o-^-D-glucopyranosyloxy)-3-(4,5-diphenylimidazol-2-yl)-chromone 4d. Yield 80 %, [a]D25 = - 1.9 (c 0.1, CH3OH). IR (KBr) v cm-1: 2945 (N-H), 2855 (glucosidic-CH), 1754 (C=O of o-acetyl gps of glycone moiety), 1722 (C=O), 1646 (C=N), 1055 (C-O-C), 689 (benzene monosubstituted). 1H NMR (DMSO-d6) SH ppm: 12.8 (s, 1'-H, N-H), 7.61 (s, 2-H, CH), 6.38-7.75 (m, 13H, Ar-H), 4.86-5.02 (m, 3H, 2", 3", 4"-H), 4.79 (d, 1H, 1"-H, anomeric proton), 4.41 (dd, 1H, 5"-H), 3.89-4.29 (m, 2H, 6"-H), 2.02, 1.91, 1.99, 2.00 (s, 3H, OAc). 13C NMR (DMSO-d) SC ppm: 175.8 (C-4, C=O), 171.0 (C-atoms of acetyl C=O), 164.1 (C-7), 160.2 (C-2), 157.1 (C-9), 135.9 (C-5'), 131.6 (C-5), 129.5 (C-2', C-3'), 128-133 (aromatic 6C-atom), 118.6 (C-3), 116.0 (C-10), 109.9 (C-6), 104.3 (C-8), 102.9 (C-1", anomeric C-atom), 75.4 (C-5"), 72.1 (C-2"), 71.3 (C-4"), 71.2 (C-3"), 66.1 (C-6"), 20.7 (C-atom, CH3 of acetyl group). EI-MS m/z (%): 711 (M+, 14), 379 (100), 136 (11), 91 (29). Anal. Calcd for C38H36N2O12: C, 64.22; H, 4.82; N, 3.94. Found: C, 64.19; H, 4.80; N, 3.90(%).
7-(2,3,4,6-Tetra-o-acetyl-o-^-D-glucopyranosyloxy)-3-[4-phenyl,5-(p-methoxyphenyl)imidazol-2-yl]-chromone 4e. Yield 89 %, [a]D25 = - 1.5 (c 0.1, CH3OH). IR (KBr) v cm-1: 2957 (N-H), 2857 (glucosidic-CH), 1776 (C=O of o-acetyl gps of glycone moiety), 1718 (C=O), 1645 (C=N), 1091 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.7 (s, 1'-H, N-H), 7.49 (s, 2-H, CH), 6.37-7.51 (m, 12H, Ar-H), 4.84-5.05 (m, 3H, 2", 3", 4"-H), 4.78 (d, 1H, 1"-H, anomeric proton), 4.41 (dd, 1H, 5"-H), 3.87-4.29 (m, 2H, 6"-H), 3.71 (s, 3H,
OCH3), 2.01, 2.00, 1.97, 2.01 (s, 3H, OAc). 13C NMR (DMSO-d6) SC ppm: 174.8 (C-4, C=O), 170.0 (C-atoms of acetyl C=O), 164.1 (C-7), 158.7 (C-2), 157.5 (C-9), 135.4 (C-5'), 131.0 (C-5), 128.9 (C-2', C-3'), 118.9 (C-3), 115.9 (C-10), 114.5-164.5 (aromatic 12C-atom), 109.7 (C-6), 103.1 (C-8), 101.9 (C-1", anomeric C-atom), 75.1 (C-5"), 71.9 (C-2"), 71.3 (C-3"), 71.1 (C-4"), 66.1 (C-6"), 56.1 (C-atom of OCH3), 21.4 (C-atom, CH3 of acetyl group). EI-MS m/z (%): 741 (M+, 21), 410 (100), 136 (11), 91 (29). Anal. Calcd for C39H38N2O13: C, 63.24; H, 4.90; N, 3.78. Found: C, 63.21; H, 4.89; N, 3.77(%).
7-(2,3,4,6-Tetra-o-acetyl-o-ß-D-glucopyranosyloxy)-3-[4,5-di(o-chlorophenyl)imidazol-2-yl]-chromone 4f. Yield 75 %, [a] D25 = - 2.4 (c 0.1, CH3OH). IR (KBr) v cm-1: 2935 (N-H), 2859 (glucosidic-CH), 1768 (C=O of o-acetyl gps of glycone moiety), 1717 (C=O), 1631 (C=N), 1074 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 12.1 (s, 1'-H, N-H), 7.49 (s, 2-H, CH), 6.44-7.41 (m, 11H, Ar-H), 4.81-4.99 (m, 3H, 2", 3", 4"-H), 4.77 (d, 1H, 1"-H, anomeric proton), 4.41 (dd, 1H, 5"-H), 3.84-4.20 (m, 2H, 6"-H), 2.00, 2.01, 1.98, 2.04 (s, 3H, OAc). 13C NMR (DMSO-d6) 5C ppm: 175.1 (C-4, C=O), 171.0 (C-atoms of acetyl C=O), 163.7 (C-7), 159.0 (C-2), 158.2 (C-9), 135.8 (C-5'), 131.6 (C-5), 128.9 (C-2', C-3'), 125-135 (aromatic 12C-atom), 119.0 (C-3), 115.8 (C-10), 109.8 (C-6), 103.4 (C-8), 101.7 (C-1", anomeric C-atom), 74.9 (C-5"), 73.1 (C-2"), 71.4 (C-3"), 71.1 (C-4"), 66.0 (C-6"), 21.4 (C-atom, CH3 of acetyl group). EI-MS m/z (%): 780 (M+, 18), 449 (100), 136 (27), 91 (19). Anal. Calcd for C38H34N2O12CL: C, 58.55; H, 4.14; N, 3.59. Found:
38 34 2 12 2 J J
C, 58.49; H, 4.07; N, 3.52(%).
7-(2,3,4,6-Tetra-o-acetyl-o-ß-D-glucopyranosyloxy)-3-[4,5-di(p-chlorophenyl)imidazol-2-yl]-chromone 4g. Yield 83 %, [a] D25 = - 4.7 (c 0.1, CH3OH). IR (KBr) v cm-1: 2975 (N-H), 2861 (glucosidic-CH), 1725 (C=O of o-acetyl gps of glycone moiety), 1700 (C=O), 1614 (C=N), 1094 (C-O-C). 1H NMR (DMSO-d6) 5H ppm: 11.8 (s, 1'-H, N-H), 7.41 (s, 2-H, CH), 6.41-7.49 (m, 11H, Ar-H), 4.78-4.98 (m, 3H, 2", 3", 4"-H), 4.87 (d, 1H, 1"-H, anomeric proton), 4.45 (dd, 1H, 5"-H), 3.81-4.26 (m, 2H, 6"-H), 2.01, 2.02, 1.97, 2.03 (s, 3H, OAc). 13C NMR (DMSO-d6) 5C ppm: 175.5 (C-4, C=O), 171.8 (C-atoms of acetyl C=O), 163Л (C-7), 159.7 (C-2),
158.8 (C-9), 135.1 (C-5'), 131.2 (C-5), 129.3 (C-2', C-3'), 125.7135.9 (aromatic 12C-atom), 119.2 (C-3), 115.1 (C-10), 109.6 (C-6),
103.9 (C-8), 101.1 (C-1", anomeric C-atom), 75.2 (C-5"), 73.6 (C-2"), 71.3 (C-3"), 70.2 (C-4"), 66.3 (C-6"), 21.1 (C-atom, CH3 of acetyl group). EI-MS m/z (%): 780 (M+, 23), 449 (100), 136 (33), 91 (25). Anal. Calcd for C38H34N2O12Cl2: C, 58.55; H, 4.14; N, 3.59. Found: C, 58.47; H, 4.07; N, 3.51(%).
7-(2,3,4,6-Tetra-o-acetyl-o-ß-D-glucopyranosyloxy)-3-[4,5-di(N,N-dimethylaminophenyl)imidazol-2-yl]-chromone 4h. Yield 80 %, [a]D25 = - 3.2 (c 0.1, CH3OH). IR (KBr) v cm-1: 2989 (N-H), 2867 (glucosidic-CH), 1729 (C=O of o-acetyl gps of glycone moiety), 1705 (C=O), 1623 (C=N), 1110 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.7 (s, 1'-H, N-H), 7.44 (s, 2-H, CH), 6.46-7.41 (m, 11H, Ar-H), 4.72-4.96 (m, 3H, 2", 3", 4"-H), 4.89 (d, 1H, 1"-H, anomeric proton), 4.48 (dd, 1H, 5"-H), 3.86-4.29 (m, 2H, 6"-H), 2.83 (s, 6H, N(CH3)2), 2.76 (s, 6H, N(CH3)2), 1.98, 2.01, 2.04, 2.00 (s, 3H, OAc). 13C NMR (DMSO-d6) 5C ppm: 175.1 (C-4, C=O), 171.3 (C-atoms of acetyl C=O), 163.4 (C-7), 159.2 (C-2), 158.2 (C-9), 135.7 (C-5'),
131.0 (C-5), 129.0 (C-2', C-3'), 125.1-135.4 (aromatic 12C-atom),
119.1 (C-3), 115.8 (C-10), 109.3 (C-6), 103.3 (C-8), 101.7 (C-1", anomeric C-atom), 75.7 (C-5"), 73.9 (C-2"), 71.4 (C-3"), 70.8 (C-4"), 66.5 (C-6"), 40.5 (N(CH3)2), 40.2 (N(CH3)2), 21.3 (C-atom, CH3 of acetyl group). Anal. Calcd for C42H44N4O12: C, 63.31; H, 5.57; N, 7.03. Found: C, 63.22; H, 5.50; Ni, 6.97(%).
7-(2,3,4,6-Tetra-o-acetyl-o-b-D-glucopyranosyloxy)-3-[4,5-di-(p-methylphenyl)imidazol-2-yl]-chromone 4i. Yield 85%, [a]D25 = -2.9 (c 0.1, CH3OH). IR (KBr) v cm-1: 2979 (N-H), 2860 (glucosidic-CH), 1733 (C=O of o-acetyl gps of glycone moiety), 1712 (C=O), 1621 (C=N), 1098 (C-O-C). 1H NMR (DMSO-d6) SH
ppm: 11.3 (s, 1'-H, N-H), 7.45 (s, 2-H, CH), 6.36-7.55 (m, 11H, Ar-H), 4.72-4.97 (m, 3H, 2", 3", 4"-H), 4.88 (d, 1H, 1"-H, anomeric proton), 4.49 (dd, 1H, 5"-H), 3.80-4.29 (m, 2H, 6"-H), 2.23 (s, 3H, CH3), 2.20 (s, 3H, CH3), 2.01, 2.02, 1.99, 2.03 (s, 3H, OAc). 13C NMR (DMSO-d6) SC ppm: 175.0 (C-4, C=O), 171.1 (C-atoms of acetyl C=O), 163.4 (C-7), 159.2 (C-2), 158.6 (C-9), 135.9 (C-5'),
131.7 (C-5), 129.0 (C-2', C-3'), 125.1-135.4 (aromatic 12C-atom),
119.8 (C-3), 115.8 (C-10), 109.2 (C-6), 103.4 (C-8), 101.8 (C-1", anomeric C-atom), 75.7 (C-5"), 73.1 (C-2"), 71.9 (C-3"), 70.5 (C-4"), 66.8 (C-6"), 24.6 (C-atom of CH3), 23.8 (C-atom of CH3), 21.9 (C-atom, CH3 of acetyl group). Anal. Calcd for C40H38N2O12: C, 65.03; H, 5.18; N, 3.79. Found: C, 64.91; H, 5.11; N, 3.78(%).
General procedure for the preparation of compounds 5a-i. The mixture of 2,3,4,6-tetra-o-acetyl-7-o-8-D-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-chromones 4a-i (0.109 mmol), dry methanol (2 ml) and anhydrous zinc acetate (0.126 mmol) was refluxed for 7-9 h (monitored by TLC). After cooled down 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 titled compound.
7-o-fi-D-Glucopyranosyloxy-3-(imidazol-2-yl)-chromone 5a. Yield 90 %, [a]D25 = - 9.1 (c 0.1, CH3OH). IR (KBr) v cm-1: 3412 (br, OH peak of carbohydrate residue), 2929 (N-H), 2853 (glucosidic-CH), 1599 (C=O), 1445 (C=N), 1089 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.7 (s, 1'-H, N-H), 7.51 (s, 2-H, CH), 7.06 (d, 2'-H, 3'-H) (CH), 6.37-7.55 (m, 3H, Ar-H), 5.74 (d, 1"-H, anomeric proton), 3.44-4.72 (m, 6H, P-D-glucopyranosyl ring). 13C NMR (DMSO-d6) SC ppm: 174.7 (C-4, C=O), 163.8 (C-7), 159.6 (C-2), 158.1 (C-9), 136.1 (C-5'), 130.8 (C-5), 127.8 (C-2', C-3'), 118.2 (C-3), 116.2 (C-10), 109.9 (C-6), 106.0 (C-1", anomeric C-atom), 104.0 (C-8), 82.1 (C-5"), 77.6 (C-3"), 74.9 (C-2"), 73.1 (C-4"), 64.0 (C-6"). EI-MS m/z (%): 391 ([M+1]+, 10), 228 (100), 136 (15), 91 (25). Anal. Calcd for C18H16N2O8: C, 55.39; H, 4.65; N, 7.18. Found: C, 55.35; H, 4.66; N, 7.16(%).
7-o-fi-D-Glucopyranosyloxy-3-(4,5-dimethylimidazol-2-yl)-chromone 5b. Yield 91 %, [a]D25 = - 10.1 (c 0.1, CH3OH). IR (KBr) v cm-1: 3446 (br, OH peak of carbohydrate residue), 2958 (N-H), 2856 (glucosidic-CH), 1598 (C=O), 1414 (C=N), 1092 (C-O-C); 1H NMR (DMSO-d6) SH ppm: 13.2 (s, 1'-H, N-H), 7.56 (s, 2-H, CH), 6.41-7.49 (m, 3H, Ar-H), 5.69 (d, 1"-H, anomeric proton), 3.454.95 (m, 6H, P-D-glucopyranosyl ring), 2.34 (s, 2'-H, CH3), 2.19 (s, 3'-H, CH3). 13C NMR (DMSO-d6) SC ppm: 176.0 (C-4, C=O), 163.5 (C-7), 159.6 (C-2), 158.1 (C-9), 135.6 (C-5'), 132.1 (C-2',C-3'), 131.1 (C-5), 118.0 (C-3), 115.1 (C-10), 109.3 (C-6), 105.0 (C-1", anomeric C-atom), 103.5 (C-8), 81.1 (C-5"), 77.7 (C-3"), 75.9 (C-2"), 73.0 (C-4"), 65.8 (C-6"), 11.9 (CH3 of C-2', C-3'). EI-MS m/z (%): 419 ([M+1]+, 7), 256 (100), 163 (18), 136 (28), 91 (16). Anal. Calcd for C20H20N2O8: C, 57.41; H, 5.30; N, 6.70. Found: C, 57.37; H, 5.27; N, 6.67(%).
7-o-fi-D-Glucopyranosyloxy-3-(4-phenylimidazol-2-yl)-chromone 5c. Yield 96 %, [a]D25 = - 15.5 (c 0.1, DMSO). IR (KBr) v cm-1: 3400 (br, OH peak of carbohydrate residue), 2925 (N-H), 2854 (glucosidic-CH), 1592 (C=O), 1404 (C=N), 1071 (C-O-C), 689 (benzene monosubstituted). 1H NMR (DMSO-d6) SH ppm: 12.7 (s, 1'-H, NH), 7.48 (s, 2-H, CH), 7.11 (s, 2'-H, CH), 6.43-8.08 (m, 8H, Ar-H), 5.85 (d, 1"-H, anomeric proton), 3.41-4.70 (m, 6H, P-d-glucopyranosyl ring). 13C NMR (DMSO-d6) SC ppm: 176.2 (C-4, C=O), 164.7 (C-7), 159.1 (C-2), 157.7 (C-9), 140.1 (C-3'), 136.4 (C-5'), 131.0 (C-5), 127.0-133.5 (aromatic 6C-atom), 121.4 (C-2'), 119.4 (C-3), 114.9 (C-10), 109.1 (C-6), 105.4 (C-1", anomeric C-atom), 103.1 (C-8), 81.2 (C-5"), 77.0 (C-3"), 75.1 (C-2"), 73.9 (C-4"), 65.7 (C-6"). EI-MS m/z (%): 467 ([M+1]+, 4), 304 (100), 227 (20), 163 (21), 136 (18), 91 (30), 77 (18). Anal. Calcd for C24H20N2O8: C, 60.57; H, 4.77; N, 4.41. Found: C, 60.54; H, 4.76; N, 4.36(%).
7-o-ß-D-Glucopyranosyloxy-3-(4,5-diphenylimidazol-2-yl)-chromone 5d. Yield 92 %, [a]D25 = - 11.9 (c 0.1, DMSO). IR (KBr) v cm-1: 3428 (br, OH peak of carbohydrate residue), 2929 (N-H), 2858 (glucosidic-CH), 1597 (C=O), 1429 (C=N), 1100 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.8 (s, 1'-H, N-H), 7.59 (s, 2-H, CH), 6.50-7.75 (m, 13H, Ar-H), 5.80 (d, 1"-H, anomeric proton), 3.43-4.78 (m, 6H, ß-D-glucopyranosyl ring). 13C NMR (DMSO-d6) 5C ppm: 176.1 (C-4, C=O), 164.5 (C-7), 160.2 (C-2), 157.1 (C-9), 136.5 (C-5'), 130.9 (C-5), 129.6 (C-2', C-3'), 127.4-133.9 (aromatic 6C-atom), 118.9 (C-3), 115.1 (C-10), 109.5 (C-6), 106.2 (C-1", anomeric C-atom), 104.1 (C-8), 81.4 (C-5"), 77.2 (C-3"), 75.2 (C-2"), 73.9 (C-4"), 64.9 (C-6"). EI-MS m/z (%): 542 (M+, 9), 379 (100), 227 (11), 163 (41), 136 (19), 91 (21), 77 (20). Anal. Calcd for C30H24N2O8: C, 64.22; H, 4.82; N, 3.94. Found: C, 64.19; H, 4.80; N, 3.90(%).
7-o-ß-D -Glucopyranosyloxy-3-[4-phenyl,5-(p-methoxyphenyl)imidazol-2-yl]-chromone 5e. Yield 89 %, [a]D25 = - 9.8 (c 0.1, DMSO). IR (KBr) v cm-1: 3411 (br, OH peak of carbohydrate residue), 2944 (N-H), 2856 (glucosidic-CH), 1593 (C=O), 1415 (C=N), 1099 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.9 (s, 1'-H, N-H), 7.51 (s, 2-H, CH), 6.39-7.48 (m, 12H, Ar-H), 5.54 (d, 1"-H, anomeric proton), 3.45-4.78 (m, 6H, ß-D-glucopyranosyl ring), 3.70 (s, 3H, OCH3). 13C NMR (DMSO-d6) SC ppm: 176.1 (C-4, C=O) 163.8 (C-7), 158.8 (C-2), 157.4 (C-9), 136.1 (C-5'),
131.4 (C-5), 129.1 (C-2', C-3'), 118.1 (C-3), 115.3 (C-10), 115-164 (aromatic 12C-atom), 110.1 (C-6), 106.1 (C-1", anomeric C-atom),
103.5 (C-8), 81.1 (C-5"), 78.1 (C-3"), 74.7 (C-2"), 73.1 (C-4"), 64.6 (C-6"), 56.0 (C-atom of OCH3). EI-MS m/z (%): 573 ([M+1]+, 11), 410 (100), 163 (29), 91 (19). Anal. Calcd for C31H26N2O8: C, 63.03; H, 4.93; N, 4.89. Found: C, 65.01; H, 4.94; N, 4.88(%).
7-o-ß-D-Glucopyranosyloxy-3-[4,5-di(o-chlorophenyl) imidazol-2-yl]-chromone 5f. Yield 85 %, [a]D25 = - 12.4 (c 0.1, DMSO). IR (KBr) v cm-1: 3454 (br, OH peak of carbohydrate residue), 2928 (N-H), 2852 (glucosidic-CH), 1591 (C=O), 1420 (C=N), 1095 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.6 (s, 1'-H, N-H), 7.55 (s, 2-H, CH), 6.40-7.51 (m, 11H, Ar-H), 5.68 (d, 1"-H, anomeric proton), 3.41-4.74 (m, 6H, ß-D-glucopyranosyl ring). 13C NMR (DMSO-d6) SC ppm: 176.1 (C-4, C=O), 165.1 (C-7), 159.0 (C-2), 158.2 (C-9), 135.6 (C-5'), 130.9 (C-5), 129.0 (C-2', C-3'), 126.5-134.5 (aromatic 12C-atom), 117.8 (C-3), 115.1 (C-10), 109.9 (C-6), 106.2 (C-1", anomeric C-atom), 104.3 (C-8), 82.4 (C-5"), 77.2 (C-3"), 75.8 (C-2"), 73.1 (C-4"), 64.1 (C-6"). EI-MS m/z (%): 612 ([M+1]+, 9), 449 (100), 163 (19), 91 (23). Anal. Calcd for C3nH.4N.O8Cl.: C, 58.93; H, 3.96; N, 4.58. Found: C, 58.90; H,
30 24 2 8 2
3.95; N, 4.55(%).
7-o-ß-D-Glucopyranosyloxy-3-[4,5-di(p-chlorophenyl) imidazol-2-yl]-chromone 5g. Yield 83 %, [a]D25 = - 13.1 (c 0.1, DMSO). IR (KBr) v cm-1: 3336 (br, OH peak of carbohydrate residue), 2988 (N-H), 2852 (glucosidic-CH), 1645 (C=O), 1443 (C=N), 1099 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.9 (s, 1'-H, N-H), 7.50 (s, 2-H, CH), 6.33-7.55 (m, 11H, Ar-H), 5.78 (d, 1"-H, anomeric proton), 3.45-4.75 (m, 6H, ß-D-glucopyranosyl ring). 13C NMR (DMSO-d6) SC ppm: 176.3 (C-4, C=O), 165.3 (C-7), 159.6 (C-2), 158.8 (C-9), 135.1 (C-5'), 130.3 (C-5), 129.4 (C-2', C-3'), 126.2-134.4 (aromatic 12C-atom), 117.4 (C-3), 115.7 (C-10), 109.4 (C-6), 106.8 (C-1", anomeric C-atom), 104.9 (C-8), 82.2 (C-5"), 77.5 (C-3"), 75.2 (C-2"), 73.6 (C-4"), 64.8 (C-6"). EI-MS m/z (%): 612 ([M+1]+, 14), 449 (100), 163 (23), 91 (34). Anal. Calcd for аддаек: C, 58.93; H, 3.96; N, 4.58. Found: C, 58.85; H,
30 24 2 8 2
3.90; N, 4.51(%).
7-o-ß-D-Glucopyranosyloxy-3-[4,5-di(N,N-dimethylamino-phenyl)imidazol-2-yl]-chromone 5h. Yield 91 %, [a]D25 = - 9.2 (c 0.1, DMSO). IR (KBr) v cm-1: 3345 (br, OH peak of carbohydrate residue), 2967 (N-H), 2859 (glucosidic-CH), 1634 (C=O), 1432 (C=N), 1150 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 11.7 (s, 1'-H, N-H), 7.50 (s, 2-H, CH), 6.45-7.56 (m, 11H, Ar-H), 5.71 (d, 1"-H,
anomeric proton), 3.35-4.74 (m, 6H, ß-D-glucopyranosyl ring), 2.87 (s, 6H, N(CH3)2), 2.81 (s, 6H, N(CH3)2). 13C NMR (DMSO-d6) SC ppm: 176.3 (C-4, C=O), 165.5 (C-7), 158.6 (C-2), 158.6 (C-9),
135.1 (C-5'), 130.5 (C-5), 129.3 (C-2', C-3'), 125.2-136.3 (aromatic 12C-atom), 117.2 (C-3), 115.8 (C-10), 110.2 (C-6), 106.7 (C-1", anomeric C-atom), 104.6 (C-8), 82.9 (C-5"), 77.9 (C-3"), 75.3 (C-2"), 73.7 (C-4"), 64.6 (C-6"), 40.7 (N(CH3)2), 40.1 (N(CH3)2). Anal. Calcd for C34H36N4O8: C, 64.96; H, 5.77; N, 8.91. Found: C,
34 36 4 8
64.85; H, 5.69; N, 8.82(%).
7-o-ß-D-Glucopyranosyloxy-3-[4,5-di(p-methylphenyl)-imidazol-2-yl]-chromone 5i. Yield 96 %, [a]D25 = - 11.1 (c 0.1, DMSO). IR (KBr) v cm-1: 3234 (br, OH peak of carbohydrate residue), 2985 (N-H), 2857 (glucosidic-CH), 1672 (C=O), 1443 (C=N), 1096 (C-O-C). 1H NMR (DMSO-d6) SH ppm: 12.2 (s, 1'-H, N-H), 7.59 (s, 2-H, CH), 6.37-7.45 (m, 11H, Ar-H), 5.79 (d, 1"-H, anomeric proton), 3.45-4.79 (m, 6H, ß-D-glucopyranosyl ring), 2.28 (s, 3H, CH3), 2.18 (s, 3H, CH3). 13C NMR (DMSO-d6) SC ppm: 176.5 (C-4, C=O), 165.4 (C-7), 159.3 (C-2), 158.9 (C-9), 135.2 (C-5'), 130.4 (C-5), 129.9 (C-2', C-3'), 126-134.5 (aromatic 12C-atom),
117.2 (C-3), 115.6 (C-10), 109.3 (C-6), 106.8 (C-1", anomeric C-atom), 104.7 (C-8), 82.1 (C-5"), 77.7 (C-3"), 75.4 (C-2"), 73.6 (C-4"), 64.8 (C-6"), 24.2 (C-atom of CH3), 23.3 (C-atom of CH3). Anal. Calcd for C„H„N,O ■ C, 67.36; H, 5.30; N, 4.91. Found: C,
32 30 2 8
67.25; H, 5.21; N, 4.81(%).
Results and Discussion
Our synthetic pathway is outlined in Scheme 1. During the course of our present research work, the starting compound 7-hydroxy-3-formyl chromone 1 was prepared by Vilsmeier-Haack reaction from resacetophenone.[25,27] The condensation of 1 with various 1,2-dicarbonyl compounds 2 in the presence of anhydrous CH3COONH4 in glacial acetic acid undergoes cyclisation results in the formation of 7-hydroxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones[28] (3a-i). The IR spectrum of 3a showed a broad peak at 3400 cm-1 due to the OH stretch; the peak at 3064 cm-1 was appeared due to N-H stretch; a strong absorption at 1622 cm-1 was assigned to C=O stretch; the peaks at 1455 and 1171 cm-1 were due to C=N and C-O-C stretches respectively. The 1H NMR spectrum exhibited three singlets at 5 5.12, 7.26, and 12.9 which readily recognised as arising from OH, C-H, and N-H respectively. The characteristic multiplets for the aromatic protons are located at 5 = 6.40-7.49. The 13C NMR spectrum of 3a showed 12 distinctive resonances in agreement with the proposed structure. The potassium salts of 3a-i for o-glucosydation were prepared by the action of anhydrous K2CO3 in the mixture of DMF and acetone (3:2 v/v) as a solvent. An interaction between the potassium salt and a-acetobromoglucose as glucosyl donor in the presence of dodecyltrimethylammonium bromide (DTMAB) as a phase transfer catalyst. This gives rise 2,3,4,6-tetra-o-acetyl-#-D-glucopyranosyloxy-3-(4,5-disubstituted imidazol-2-yl)-4H-chromen-4-ones 4a-i. The absence of IR band in 4a due to OH stretch at 3400 cm-1 is indicating the formation of product. Further, the peaks at 3056 and 2924 cm-1 were due to the C-H and N-H stretches respectively. The C=O stretch peak was found to be shifted to 1729 cm-1. A strong absorption at 1757 cm-1 was assigned to C=O stretch of o-acetyl groups of glucose moiety. The peaks at 1621 and 1037 cm-1 were attributed to the C=N and C-O-C stretches respectively. A sharp peak at 2853 cm-1 was assigned to glucosidic C-H stretch. The 1H NMR spectrum exhibited
HO.
CHO
O^R
HO,
O
H OAc
____JH-O
AcO
AcO ^—- O,
OAc HH
H OH
HH
m
O
N R' I
H
m
O
N R' I
H
N R' 1
O H
R R'
a) H H
b) CH 3 CH 3
c) C6H5 H
d) C6H5 C6H5
e) C6H5 4-OC H3C6H4
f) 2-ClC6H4 2-ClC6H4
g) 4-ClC6H4 4-ClC6H4
h) 4-N(CH 3)^4 4-N(CH3)2C6H
i) 4-CH3C6H4 4-CH3C6H4
Scheme 1. Synthesis of 7-o-ß-D-glucopyranosyloxy-3-(4, 5-disubstituted imidazol-2-yl)-4H-chromen-4-ones 5. Reagents: (a) CH3COONH4, CH3COOH; (b) K2CO3, DMF, (CH3)2CO; (c) DTMAB, a-acetobromoglucose; (d) Zn(CH3COO)2, MeOH.
2
1
R
4
d
R
5
signals at 5 12.5 (s, 1'-H, N-H), 7.46 (s, 2-H, CH), 7.15 (d, 2'-H, 3'-H) (CH), 6.44-7.43 (m, 3H, Ar-H), 4.87-5.00 (m, 3H, 2", 3", 4"-H), 4.76 (d, 1H, 1"-H, anomeric proton), 4.39 (dd, 1H, 5"-H), 3.86-4.24 (m, 2H, 6"-H), 2.01, 1.95, 1.99, 2.05 (s, 3H, OAc). Similarly, 13C data of the acetylated p-glucosides (4a-i) were in agreement with the assigned structures.
We tried to deacetylate of 4a-i by standard procedure using NaOMe/MeOH;[29] however, we found that the strong basic condition resulted in cleavage of the isoflavone's C-ring, while the anhydrous zinc acetate in absolute methanol system led to significant deglycosylation. Finally, complete deacetylation of 4a-i was achieved by using anhydrous zinc acetate in absolute methanol yielded corresponding o-#-D-glucosides 5a-i in good yields. The IR spectrum of 5a showed the presence of characteristic absorption peaks at 3412, 2929, 2853, 1599, 1445, and 1089 due to OH of carbohydrate residue, N-H, glucosidic C-H, C=O, C=N, and ether linkage respectively. The 'H NMR data showed the presence of carbohydrate moiety. The chemical shift of the anomeric proton show p-linkage at 5 5.74 (C-H) indicating the linkage of carbohydrate unit to C-7 position of the aglycone. The compounds gave satisfactory C, H and N analysis. The mass spectrum of 5a displayed the molecular ion peak [M+1]+ at m/z = 391, which is consistent with its proposed structure.
Conclusions
In conclusion we have synthesized the newly synthesized glucosides of 7-hydroxy-3-(4,5-disubstituted imidazol-2-yl)-4^-chromen-4-ones with promising yield.
Acknowledgments. The authors are thankful to the Director, SAIF, Chandigarh and the Head, Department of Chemistry, IIT-Pawai, Mumbai for providing necessary spectral analysis and the Head, Department of Chemistry, R T M Nagpur University, Nagpur for providing necessary laboratory facilities.
References
1. Nicolaou K.C., Mitchell H.J. Angew. Chem. Int. Ed. 2001, 40, 1576.
2. Sears P., Wong C-H. Chem. Commun. 1998, 1161.
3. Varki A. Glycobiology 1993, 3, 97.
4. Hakomori S-I. Acta. Anat. 1998, 161, 79.
5. Rademacher T.W., Parekh R.B., Dwek R.A. Glycobiology. Annu. Rev. Biochem. 1988, 57, 785.
6. Varki A., Cummings R. Essentials of Glycobiology. Cold Spring Harbor Laboratory Press, Plainview, NY, 1999.
7. Giannis A. Angew. Chem. 1994, 106, 188; Angew. Chem. Int. Ed. Engl. 1994, 33, 178.
8. Karlsson K.A. Trends. Pharmaco. Sci. 1991, 12, 265.
9. Hart G.W. Cur. Opin. Cell. Biol. Sci. 1992, 4, 1017.
10. Gagneau P., Varki A. Glycobiology 1999, 9, 747.
11. Feizi T., Childs R.A. Trends Biochem. Sci. 1985, 10, 24.
12. Birt D.F., Hendrich S., Wang W. Pharmaco. Ther. 2001, 90, 157.
13. Lopez-Lazaro M. Cur. Med. Chem. - Anti-Cancer Agents 2002, 2, 691.
14. Pouget C., Lauthier F., Simon A., Fagnere C., Basly J.-P., Delage C., Chulia A.-J. Bioorg. Med. Chem. Lett. 2001, 11, 3095.
15. Zheng X., Meng W.D., Xu Y.Y., Cao J.G., Qing F.L. Bioorg. Med. Chem. Lett. 2003, 13, 881.
16. Gobbi S., Rampa A., Bisi A., Belluti F., Piazzi L., Valenti P., Caputo A., Zampiron A., Carrara M. J. Med. Chem. 2003, 46, 662.
17. Atassi G., Briet P., Berthelon J.J., Collonges F. Eur. J. Med. Chem. Chim. Ther. 1985, 20, 393.
18. Yu D., Chen C.H., Brossi A., Lee K.H. J. Med. Chem. 2004, 47, 4072.
19. Hu C., Chen K., Shi Q., Kilkuskie R.E., Chen Y., Lee K.H. J. Nat. Prod. 1994, 57, 42.
20. Ungwitayatorn J., Samee W., Pimthon J. J. Mol. Struct. 2004, 689, 99.
21. Burda S., Oleszek W. J. Agric. Food. Chem. 2001, 49, 2774.
22. Rackova L., Firakova S., Kostalova D., Stefek M., Sturdik E., Majekova M. Bioorg. Med. Chem. 2005, 13, 6477.
23. Soobrattee M.A., Neergheen V.S., Luximon-Ramma A., Aruoma O.I., Bahorun T. Mutat. Res. 2005, 579, 200.
24. Elks J., Ganellin C.R. Dictionary of Drugs (Chemical data, structure and bibliographies), Chapman and Hall, Scientific data division, London, 1990.
25. a) Ingle V.N., Hatzade K.M., Taile V.S., Gaidhane P.K., Kharche S.T. J. Carbohydrate Chem. 2007, 26(2), 107-123; b) Hatzade K.M., Taile V.S., Gaidhane P.K., Haldar A.G.M., Ingle V.N. Indian J. Chem. 2008, 47B, 1260-1270; c) Hatzade K.M., Taile V.S., Gaidhane P.K., Umare V.D., Haldar A.G.M., Ingle V.N. Indian J. Chem. 2009, 48B, 1548; d) Hatzade K.M., Taile V.S., Gaidhane P.K., Ingle V.N. Turkish J. Chem. 2010, 34, 241.
26. Furniss B.S., Hannaford A.N., Smith P.G., Tatechell A.R. Vogels Textbook of Practical Organic Chemistry, 5th Ed.; EL/ BS, Longman, London. 1989, 807.
27. a) Nohara A., Umetani T., Sanmo Y. Tetrahedron Lett. 1974, 30, 3553; b) Lacova M., Loos D., Furdikl M., Matulova M., El-Shaaer Hafez M. Synth. Molecules 1998, 3, 149.
28. Grimmett M.R. Imidazole and Benzimidazole Synthesis. Academic Press, London. 1997, 151.
29. Lewis P., Haltia S., Wahala K. J. Chem. Soc. Perkins Trans 1 1998, 16, 2481.
Received 16.10.2012 Accepted 21.12.2012
