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【结 构 式】 
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【药物名称】 【化学名称】7-[6-Deoxy-4-O,5-dimethyl-3-O-(5-methyl-1H-pyrrol-2-ylcarbonyl)-alpha-L-mannopyranosyloxy]-4-[2-(1H-imidazol-2-ylsulfanyl)ethoxy]-8-methyl-2H-1-benzopyran-2-one 【CA登记号】 【 分 子 式 】C29H33N3O9S 【 分 子 量 】599.66506 |
【开发单位】Aventis Pharma (Originator) 【药理作用】Antibacterial Drugs, ANTIINFECTIVE THERAPY, DNA Gyrase Inhibitors |
合成路线1
4,7-Dihydroxy-8-methylcoumarin (I) was selectively protected as the monosilylated derivative (II) using tert-butyldiphenylsilyl chloride and Et3N. Subsequent Mitsunobu coupling of (II) with 2-bromoethanol (A) produced the bromoethoxy coumarin (III). After desilylation of (III) with a mixture of HF and KF, the resulting phenol (IV) was coupled with noviose triol (V) under Mitsunobu conditions to afford the alpha-glycoside (VI) as the major isomer. Esterification of (VI) with 5-methylpyrrole-2-carboxylic anhydride (VII) in the presence of CoCl2 yielded the desired 3'-ester (VIII) along with minor amounts of 2'-ester, which was separated by column chromatography. Finally, displacement of the bromide of (VIII) by 2-mercaptoimidazole (IX) furnished the corresponding thioether.
| 【1】 Ferroud, D.; Laurin, P.; Schio, L.; et al.; Structure-activity relationship in two series of aminoalkyl substituted coumarin inhibitors of gyrase B. Bioorg Med Chem Lett 1999, 9, 19, 2875. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (A) | 10059 | Ethylene bromohydrin; 2-Bromo-1-ethanol | 540-51-2 | C2H5BrO | 详情 | 详情 |
| (I) | 40543 | 4,7-dihydroxy-8-methyl-2H-chromen-2-one | C10H8O4 | 详情 | 详情 | |
| (II) | 40544 | 7-[[tert-butyl(diphenyl)silyl]oxy]-4-hydroxy-8-methyl-2H-chromen-2-one | C26H26O4Si | 详情 | 详情 | |
| (III) | 40545 | 4-(2-bromoethoxy)-7-[[tert-butyl(diphenyl)silyl]oxy]-8-methyl-2H-chromen-2-one | C28H29BrO4Si | 详情 | 详情 | |
| (IV) | 40546 | 4-(2-bromoethoxy)-7-hydroxy-8-methyl-2H-chromen-2-one | C12H11BrO4 | 详情 | 详情 | |
| (V) | 40547 | (3R,4S,5R)-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2,3,4-triol | C8H16O5 | 详情 | 详情 | |
| (VI) | 40548 | 4-(2-bromoethoxy)-7-[[(2R,3R,4S,5R)-3,4-dihydroxy-5-methoxy-6,6-dimethyltetrahydro-2H-pyran-2-yl]oxy]-8-methyl-2H-chromen-2-one | C20H25BrO8 | 详情 | 详情 | |
| (VII) | 40549 | 5-methyl-1H-pyrrole-2-carboxylic anhydride | C12H12N2O3 | 详情 | 详情 | |
| (VIII) | 40550 | (3R,4S,5R,6R)-6-[[4-(2-bromoethoxy)-8-methyl-2-oxo-2H-chromen-7-yl]oxy]-5-hydroxy-3-methoxy-2,2-dimethyltetrahydro-2H-pyran-4-yl 5-methyl-1H-pyrrole-2-carboxylate | C26H30BrNO9 | 详情 | 详情 | |
| (IX) | 34456 | 1H-imidazole-2-thiol; 1H-imidazol-2-ylhydrosulfide | 872-35-5 | C3H4N2S | 详情 | 详情 |