الفهرس 
IntroductionOnly 14 pages are availabe for public view
 |  | from | 134 |  |  |
| | | from | 134 | | |
Abstract
ENGLISH SUMMARY Treatment of 2-aminobenzoic acid (anthranilic acid) (137) with phenylisothiocyanate in ethanol at reflux temperature afforded 3-phenyl- 2-thioxoquinazolin-4(1H)-one (138) (Scheme 1). The sodium salt of 138 was condensed with 2-acetamido-1-chloro- 3,4,6-tri-O-acetyl-2-deoxy-α-D-glucose (139) in dry DMF. The reaction was proceeded at 90 oC to give the desired 2-(2-acetamido-3,4,6-tri-Oacetyl- 2-deoxy-β-D-glucopyranosylsulphanyl)-3-phenylquinazolin- 4(1H)-one (140) in 81 % yield. Deacetylation of 140 in a mixture of methanol and ammonium hydroxide (25 %) (1:1) at room temperature afforded 2-(2-acetamido-2- deoxy-β-D-glucopyranosylsulphanyl)-3-phenylquinazolin-4(1H)-one (141) in 88 % yield (Scheme 2). 138 NH N O Ph S 1. NaH/DMF 2. O Cl NHAc AcO AcO AcO 139 N N O Ph O AcO NHAc AcO AcO 140 S NH3/MeOH N N O Ph O HO NHAc HO HO 141 S Scheme 2 The sodium salt of 138 was condensed with 2,3,4,6-tetra-O-acetyl- α-D-glucopyranosyl bromide (142) in dry DMF. The reaction was proceeded at 90 oC to give the desired 2-(2,3,4,6-tetra-O-acetyl-β-Dglucopyranosylsulphanyl)- 3-phenylquinazolin-4(1H)-one (143) in 83 % yield. Deacetylation of 143 in a mixture of methanol and ammonium hydroxide (25 %) (1:1) at room temperature afforded 2-(β-Dglucopyranosylsulphanyl)- 3-phenylquinazolin-4(1H)-one (144) in 95 % yield (Scheme 3). Treatment of the sodium salt of 138 with 2,3,4,6-tetra-O-acetyl-α- D-galactopyranosyl bromide (145) in dry DMF at 90 oC afforded 2- (2,3,4,6-tetra-O-acetyl-β-D-galactopyranosylsulphanyl)-3-phenylquinazolin- 4(1H)-one (146) in 80 % yield. Deacetylation of 146 in a mixture of methanol and ammonium hydroxide (25 %) (1:1) at room temperature afforded 2-(β-Dgalactopyranosylsulphanyl)- 3-phenylquinazolin-4(1H)-one (147) in 93 % yield (Scheme 4). Treatment of 138 with acrylonitrile in ethanol and in the presence of triethylamine at reflux temperature afforded 3-phenyl-1-propanenitrile- 2-thioxoquinazolin-4(1H)-one (148) in 72 % yield. 1-[2-(2H-Tetrazol-5-yl)ethyl]-3-phenyl-2-thioxoquinazolin-4(1H)- one (149) was produced in 89 % yield by treating of 148 with sodium azide and ammonium chloride in DMF at 120 oC. Treatment of 148 with hydrazine hydrate in ethanol at reflux temperature gave 1-[(2H)-propanimidhydrazide]-3-phenyl-2- thioxoquinazolin-4(1H)-one (150) in 85 % yield (Scheme 5). 138 NH N O Ph S Scheme 5 CH2=CHCN/TEA EtOH/Reflux 148 N N O Ph S CN NaN3/NH4Cl DMF 149 N N O Ph S N N NH N NH2NH2.H2O EtOH/Reflux 150 N N O Ph S H2NHN NH The tetrazole derivative 149 was allowed to react with ethyl chloroacetate in dry acetone and in the presence of anhydrous potassium carbonate to afford ethyl 2-{5-[2-(4-oxo-3-phenyl-2-thioxo3,4- dihydroquinazolin-1(2H)-yl)ethyl]-2H-tetrazole-2-yl}acetate (151) in 90% yield. 2-{5-[2-(4-Oxo-3-phenyl-2-thioxo3,4-dihydroquinazolin-1(2H)- yl)ethyl]-2H-tetrazole-2-yl}acetohydrazide (152) was synthesized, in 94% yield, by refluxing its corresponding ester derivative 151 with hydrazine hydrate in ethanol. Compounds 151 and 152 were confirmed by I.R, 1H NMR, and mass spectra which agreed with the assigned structures (Scheme 6). When the hydrazide 152 was reacted with the respective monosaccharides (D-xylose, D-arabinose or D-galactose) in an aqueous ethanolic solution and a catalytic amount of glacial acetic acid, gave the corresponding hydrazinosugar derivatives 153-155 in 81-87 % yields, respectively. Acetylation of the sugar hydrazones 153-155 with acetic anhydride in pyridine at room temperature gave the corresponding per-O-acetyl derivatives 156-158 in 94-97% yields. Heating of the sugar hydrazones 153-155 with acetic anhydride at 120 oC for 1.5 h afforded the corresponding oxadiazoline derivatives 159- 161 in 85-86% yields. The sugar derivatives 153-161 were confirmed by I.R, 1H NMR, and mass spectra which agreed with the assigned structures (Scheme 7). When the hydrazide 152 was reacted with the aromatic aldehydes in an aqueous ethanolic solution and a catalytic amount of glacial acetic acid, gave the corresponding benzylidene acetohydrazides 162-164 in 69- 74 % yields, respectively. The benzylidene derivatives 162-164 were confirmed by I.R, 1H NMR, and mass spectra which agreed with the assigned structures (Scheme 8). The antitumor and antimicrobial activities of the prepared compounds were evaluated. The free hydroxyl thioglycosyl derivatives as well as the sugar hydrazones analogues were the highly active compounds.