【结 构 式】 |
【分子编号】54166 【品名】{(2S,3S,4R,5S)-3-(benzoyloxy)-4-fluoro-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl benzoate 【CA登记号】n/a |
【 分 子 式 】C24H21FN2O7 【 分 子 量 】468.4384232 【元素组成】C 61.54% H 4.52% F 4.06% N 5.98% O 23.91% |
合成路线1
该中间体在本合成路线中的序号:(XI)A new synthesis of clevudine has been described: Peracetylation of L-arabinose (I) with acetic anhydride and pyridine provides acetylated arabinose (II), which is then brominated by means of HBr in AcOH/Ac2O to furnish the bromo-sugar (III). Treatment of the sugar (III) with Zn dust, CuSO4 and NaOAc in AcOH/H2O, followed by chromatographic separation, gives L-arabinal (IV), which is then converted to the fluoro derivative (V) by reaction with Selectfluor?(F-TEDA-BF4) in refluxing nitromethane/H2O. Deacetylation of compound (V) with NaOMe in MeOH yields compound (VI), which is then converted into the methyl furanoside (VII) by treatment with H2SO4 in MeOH. Benzoylation of the furanoside (VII) with benzoyl chloride in pyridine affords a mixture of isomers, from which (VIII) is separated by chromatography and then brominated with HBr/AcOH in CH2Cl2 to provide the bromo-sugar (IX). Condensation of the sugar (IX) with the silylated pyrimidine derivative (X) in refluxing chloroform affords 3,5-di-O-benzoylclevudine (XI), which is finally deprotected by treatment with n-butylamine in refluxing methanol. Compound (X) is obtained by treatment of thymine (XII) with HMDS (1,1,1,3,3,3-hexamethyldisilazane) and ammonium sulfate in refluxing chloroform.
【1】 Almond, M.R.; Pesyan, A.; Sznaidman, M.L.; New synthesis of L-FMAU from L-arabinose. Nucleosides Nucleotides Nucleic Acids 2002, 21, 2, 155. |
中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
---|---|---|---|---|---|---|
(I) | 17520 | (3R,4S,5S)tetrahydro-2H-pyran-2,3,4,5-tetrol; L-(+)-Arabinose | 7296-56-2 | C5H10O5 | 详情 | 详情 |
(II) | 48936 | D-Arabinose tetraacetate | C13H18O9 | 详情 | 详情 | |
(III) | 54161 | (2R,3R,4S,5S)-3,5-bis(acetyloxy)-2-bromotetrahydro-2H-pyran-4-yl acetate | n/a | C11H15BrO7 | 详情 | 详情 |
(IV) | 54162 | (3S,4R)-3-(acetyloxy)-3,4-dihydro-2H-pyran-4-yl acetate | n/a | C9H12O5 | 详情 | 详情 |
(V) | 54163 | (3R,4S,5S)-5-(acetyloxy)-3-fluoro-2-hydroxytetrahydro-2H-pyran-4-yl acetate | n/a | C9H13FO6 | 详情 | 详情 |
(VI) | 54164 | (3R,4S,5S)-3-fluorotetrahydro-2H-pyran-2,4,5-triol | n/a | C5H9FO4 | 详情 | 详情 |
(VII) | 54167 | (2S,3S,4R)-4-fluoro-2-(hydroxymethyl)-5-methoxytetrahydro-3-furanol | n/a | C6H11FO4 | 详情 | 详情 |
(VIII) | 54165 | [(2S,3S,4R,5R)-3-(benzoyloxy)-4-fluoro-5-methoxytetrahydro-2-furanyl]methyl benzoate | n/a | C20H19FO6 | 详情 | 详情 |
(IX) | 17524 | [(2S,3S,4R,5S)-3-(benzoyloxy)-5-bromo-4-fluorotetrahydro-2-furanyl]methyl benzoate | C19H16BrFO5 | 详情 | 详情 | |
(X) | 41900 | 5-methyl-2,4-bis[(trimethylsilyl)oxy]pyrimidine; 5-methyl-2-[(trimethylsilyl)oxy]-4-pyrimidinyl trimethylsilyl ether | 7288-28-0 | C11H22N2O2Si2 | 详情 | 详情 |
(XI) | 54166 | {(2S,3S,4R,5S)-3-(benzoyloxy)-4-fluoro-5-[5-methyl-2,4-dioxo-3,4-dihydro-1(2H)-pyrimidinyl]tetrahydro-2-furanyl}methyl benzoate | n/a | C24H21FN2O7 | 详情 | 详情 |
(XII) | 12204 | 5-Methyl-2,4(1H,3H)-pyrimidinedione; Thymine | 65-71-4 | C5H6N2O2 | 详情 | 详情 |