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【结 构 式】 
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【分子编号】30694 【品名】2,2,2-trifluoro-N-[(2S,4S,6R)-6-methoxy-2-methyl-3-oxotetrahydro-2H-pyran-4-yl]acetamide 【CA登记号】 |
【 分 子 式 】C9H12F3NO4 【 分 子 量 】255.1938296 【元素组成】C 42.36% H 4.74% F 22.33% N 5.49% O 25.08% |
合成路线1
该中间体在本合成路线中的序号：(III)A suspension of methyl 2,3,6-trideoxy-3-amino-alpha-L-lyxo-hexopyranoside (I) is acylated with trifluoroacetic anhydride in ether yielding methyl 2,3,6-trideoxy-3-trifluoroacetamido-alpha-L-lyxo-hexopyranoside (II), which is oxidized with potassium periodate and ruthenium dioxide in CH2Cl2 water to afford methyl 2,3,6-trideoxy-3-trifluoroacetamido-alpha-L-threo-hexapyranosid-4-ulose (III). The reduction of (III) with NaBH4 in dioxane-water gives methyl 2,3,6-trideoxy-3-trifluoroacetamido-alpha-L-arabino-hexopyranoside (IV), which is demethylated by treatment with aqueous acetic acid to yield 2,3,6-trideoxy-4-trifluoroacetamido-alpha-L-arabino-hexopyranose (V). Acylation of (V) with trifluoroacetic anhydride in ether affords 2,3,6-trideoxy-3-trifluoroacetamido-1,4-di-O-trifluoroacetyl-alpha-L-arabino-hexopyranose (VI), which by treatment with dry HCl in ether is converted into 2,3,6-trideoxy-3-trifluoroacetamido-4-O-trifluoroacetyl-alpha-L-arabino-hexopyranosyl chloride (VII). The condensation of (VII) with 9-deacetyl-9-(2',2'-dimethyl-4'-methoxydioxolan-4'-yl)daunomycinone (VIII) [prepared from adriamycinone (IX) and 2,2-dimethoxypropane-p-toluenesulfonic acid in dioxane - CHCl3] by means of HgO and HgBr2 in CH2Cl2 gives 4'-epi-3'-N-trifluoroacetyladriamycin protected in the hydroxylacetyl group (X). Finally, this compound is deprotected by treatment with NaOH in acetone water.
| 【1】 Franchi, G.; Formelli, F.; Redaelli, S.; Dasdia, T.; Soranzo, C.; Arcamone, F.; Penco, S.; Casazza, A.M.; Vigevani, A.; Di Marco, A.; Necco, A.; Synthesis and antitumor properties of new glycosides daunomycin and daunorubicin. J Med Chem 1975, 18, 7, 703-707. |
| 【2】 Serradell, M.N.; Castaner, J.; Hopkins, S.J.; Blancafort, P.; Epirubicin. Drugs Fut 1983, 8, 5, 402. |
| 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) | 30692 | (2S,3S,4S,6R)-4-amino-6-methoxy-2-methyltetrahydro-2H-pyran-3-ol | C7H15NO3 | 详情 | 详情 | |
| (II) | 30693 | 2,2,2-trifluoro-N-[(2S,3S,4S,6R)-3-hydroxy-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl]acetamide | C9H14F3NO4 | 详情 | 详情 | |
| (III) | 30694 | 2,2,2-trifluoro-N-[(2S,4S,6R)-6-methoxy-2-methyl-3-oxotetrahydro-2H-pyran-4-yl]acetamide | C9H12F3NO4 | 详情 | 详情 | |
| (IV) | 30695 | 2,2,2-trifluoro-N-[(2S,3R,4S,6R)-3-hydroxy-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl]acetamide | C9H14F3NO4 | 详情 | 详情 | |
| (V) | 30696 | N-[(2S,3R,4S,6R)-3,6-dihydroxy-2-methyltetrahydro-2H-pyran-4-yl]-2,2,2-trifluoroacetamide | C8H12F3NO4 | 详情 | 详情 | |
| (VI) | 30697 | (2S,3R,4S,6S)-2-methyl-4-[(2,2,2-trifluoroacetyl)amino]-6-[(2,2,2-trifluoroacetyl)oxy]tetrahydro-2H-pyran-3-yl 2,2,2-trifluoroacetate | C12H10F9NO6 | 详情 | 详情 | |
| (VII) | 30698 | (2S,3R,4S,6S)-6-chloro-2-methyl-4-[(2,2,2-trifluoroacetyl)amino]tetrahydro-2H-pyran-3-yl 2,2,2-trifluoroacetate | C10H10ClF6NO4 | 详情 | 详情 | |
| (VIII) | 30699 | (8S,10S)-6,8,10,11-tetrahydroxy-1-methoxy-8-[(4R)-4-methoxy-2,2-dimethyl-1,3-dioxolan-4-yl]-7,8,9,10-tetrahydro-5,12-naphthacenedione | C25H26O10 | 详情 | 详情 | |
| (IX) | 30700 | (8S,10S)-8-glycoloyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | C21H18O9 | 详情 | 详情 | |
| (X) | 30701 | 2,2,2-trifluoro-N-[(2S,3R,4S,6R)-3-hydroxy-2-methyl-6-([(1S,3S)-3,5,12-trihydroxy-10-methoxy-3-[(4R)-4-methoxy-2,2-dimethyl-1,3-dioxolan-4-yl]-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy)tetrahydro-2H-pyran-4-yl]acetamide | C33H36F3NO13 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)
| 【1】 Van Der Rijst M, Scheeren JW, et aL.1998. A process for preparing epirubicin or acid addition salts thereof from daunorubicin. EP 848009 |
| 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) | 66341 | (8S,10S)-8-acetyl-10-((4-amino-5-hydroxy-6-methyltetrahydro-2H-pyran-2-yl)oxy)-6,8,11-trihydroxy-1-methoxy-7,8,9,10-tetrahydrotetracene-5,12-dione hydrochloride | C27H29NO10.HCl | 详情 | 详情 | |
| (II) | 16223 | (8S,10S)-8-acetyl-6,8,10,11-tetrahydroxy-1-methoxy-7,8,9,10-tetrahydro-5,12-naphthacenedione | 21794-55-8 | C21H18O8 | 详情 | 详情 |
| (III) | 66342 | 4-amino-6-methoxy-2-methyltetrahydro-2H-pyran-3-ol hydrochloride | C7H15NO3.HCl | 详情 | 详情 | |
| (IV) | 66346 | 2-oxo-2-(2,4,5,12-tetrahydroxy-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl)ethyl acetate | C23H20O10 | 详情 | 详情 | |
| (V) | 30693 | 2,2,2-trifluoro-N-[(2S,3S,4S,6R)-3-hydroxy-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl]acetamide | C9H14F3NO4 | 详情 | 详情 | |
| (VI) | 30694 | 2,2,2-trifluoro-N-[(2S,4S,6R)-6-methoxy-2-methyl-3-oxotetrahydro-2H-pyran-4-yl]acetamide | C9H12F3NO4 | 详情 | 详情 | |
| (VII) | 30695 | 2,2,2-trifluoro-N-[(2S,3R,4S,6R)-3-hydroxy-6-methoxy-2-methyltetrahydro-2H-pyran-4-yl]acetamide | C9H14F3NO4 | 详情 | 详情 | |
| (VIII) | 30696 | N-[(2S,3R,4S,6R)-3,6-dihydroxy-2-methyltetrahydro-2H-pyran-4-yl]-2,2,2-trifluoroacetamide | C8H12F3NO4 | 详情 | 详情 | |
| (IX) | 66343 | 5-hydroxy-6-methyl-4-(2,2,2-trifluoroacetamido)tetrahydro-2H-pyran-2-yl 2,2,2-trifluoroacetate | C10H11F6NO5 | 详情 | 详情 | |
| (X) | 66344 | 2-oxo-2-(2,5,12-trihydroxy-4-((5-hydroxy-6-methyl-4-(2,2,2-trifluoroacetamido)tetrahydro-2H-pyran-2-yl)oxy)-7-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-2-yl)ethyl acetate | C31H30F3NO13 | 详情 | 详情 | |
| (XI) | 66345 | 2,2,2-trifluoro-N-(3-hydroxy-2-methyl-6-((3,5,12-trihydroxy-3-(2-hydroxyacetyl)-10-methoxy-6,11-dioxo-1,2,3,4,6,11-hexahydrotetracen-1-yl)oxy)tetrahydro-2H-pyran-4-yl)acetamide | C29H28F3NO12 | 详情 | 详情 | |
| (XII) | 30701 | 2,2,2-trifluoro-N-[(2S,3R,4S,6R)-3-hydroxy-2-methyl-6-([(1S,3S)-3,5,12-trihydroxy-10-methoxy-3-[(4R)-4-methoxy-2,2-dimethyl-1,3-dioxolan-4-yl]-6,11-dioxo-1,2,3,4,6,11-hexahydro-1-naphthacenyl]oxy)tetrahydro-2H-pyran-4-yl]acetamide | C33H36F3NO13 | 详情 | 详情 |