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【结 构 式】 
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【药物名称】 【化学名称】5-Fluoro-1-[4-(hydroxymethyl)-2,5-dihydro-2-furanyl]-1,2,3,4-tetrahydropyrimidine-2,4-dione 【CA登记号】 【 分 子 式 】C9H9FN2O4 【 分 子 量 】228.18148 |
【开发单位】Ewha Womans University (Originator), Korea Res. Inst. Chem. Technol. (Originator), Yonsei University (Originator) 【药理作用】Anti-Cytomegalovirus Drugs, ANTIINFECTIVE THERAPY, Antiviral Drugs |
合成路线1
Catalytic hydrogenation of dihydrofuranone (I) over Pd/C afforded the saturated lactone (II). Treatment of (II) with chlorotrimethylsilane and lithium hexamethyldisilazide produced the silyl enol ether (III) which, without isolation, was treated with phenylselenenyl bromide to yield the trans-selenide (IV). Lactone reduction by means of DIBAL followed by acetylation of the resulting lactol (Va-b) gave acetate (VIa-b). The glycosylation of the silylated fluorouracil (VII) with (VIa-b) in the presence of trimethylsilyl triflate furnished adduct (VIIIa-b). Subsequent oxidative elimination of the phenylselenenyl group of (VIIIa-b) via an intermediate selenoxide produced the dihydrofuran derivative (IX), which was finally desilylated by treatment with tetrabutylammonium fluoride.
| 【1】 Kim, H.O.; Moon, H.R.; Lee, C.-K.; Jeong, L.S.; Choi, W.J.; Chun, M.W.; Hong, J.H.; Yoo, S.J.; Synthesis and structure-activity relationships of novel apio and thioapio dideoxydidehydronucleosides as anti-HCMV agents. J Med Chem 2001, 44, 5, 806. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (Va) | 47855 | (2R,3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2-furanol | C27H32O3SeSi | 详情 | 详情 | |
| (Vb) | 47856 | (2S,3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2-furanol | C27H32O3SeSi | 详情 | 详情 | |
| (VIa) | 47857 | (2S,3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2-furanyl acetate | C29H34O4SeSi | 详情 | 详情 | |
| (VIb) | 47858 | (2R,3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2-furanyl acetate | C29H34O4SeSi | 详情 | 详情 | |
| (VIIIa) | 47860 | 1-[(2R,3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione | C31H33FN2O4SeSi | 详情 | 详情 | |
| (VIIIb) | 47861 | 1-[(2S,3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)tetrahydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione | C31H33FN2O4SeSi | 详情 | 详情 | |
| (I) | 47851 | 4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2(5H)-furanone | C21H24O3Si | 详情 | 详情 | |
| (II) | 47852 | 4-([[tert-butyl(diphenyl)silyl]oxy]methyl)dihydro-2(3H)-furanone | C21H26O3Si | 详情 | 详情 | |
| (III) | 47853 | tert-butyl(diphenyl)silyl [5-[(trimethylsilyl)oxy]-2,3-dihydro-3-furanyl]methyl ether; [[4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-4,5-dihydro-2-furanyl]oxy](trimethyl)silane | C24H34O3Si2 | 详情 | 详情 | |
| (IV) | 47854 | (3S,4S)-4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-3-(phenylselanyl)dihydro-2(3H)-furanone | C27H30O3SeSi | 详情 | 详情 | |
| (VII) | 47859 | 5-fluoro-2-[(trimethylsilyl)oxy]-4-pyrimidinyl trimethylsilyl ether; 5-fluoro-2,4-bis[(trimethylsilyl)oxy]pyrimidine | 17242-85-2 | C10H19FN2O2Si2 | 详情 | 详情 |
| (IX) | 47862 | 1-[4-([[tert-butyl(diphenyl)silyl]oxy]methyl)-2,5-dihydro-2-furanyl]-5-fluoro-2,4(1H,3H)-pyrimidinedione | C25H27FN2O4Si | 详情 | 详情 |