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【结 构 式】 
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【分子编号】45587 【品名】2-(trimethylsilyl)ethyl (3S,4S,6S)-4-hydroxy-6-[[(2R,3S,4R,5R,6R)-4,5,6-trihydroxy-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl(methyl)carbamate 【CA登记号】 |
【 分 子 式 】C19H37NO10Si 【 分 子 量 】467.58902 【元素组成】C 48.81% H 7.98% N 3% O 34.22% Si 6.01% |
合成路线1
该中间体在本合成路线中的序号：(VII)The Grignard condensation of pyrrolinedione (I) with 7-chloroindol-1-ylmagnesium bromide (II) in toluene gives the monoaddition product (III), which is condensed with indol-1-ylmagnesium bromide (IV) to yield the disubstituted compound (V). The hydrogenation of (V) with H2 over Pd/C in DMF affords the tetrahydro derivative (VI), which is condensed with the aminosugar (VII) in DMF and dehydrogenated with DDQ or DBU to afford the adduct (VIII). Finally, the methylamino group of (VIII) is deprotected by means of TBAF in THF.
| 【1】 Van Vranken, D.L.; Chisholm, J.D.; Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1. J Org Chem 2000, 65, 22, 7541. |
| 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) | 31468 | 3,4-dibromo-1-methyl-1H-pyrrole-2,5-dione | C5H3Br2NO2 | 详情 | 详情 | |
| (II) | 45582 | bromo(7-chloro-1H-indol-1-yl)magnesium | C8H5BrClMgN | 详情 | 详情 | |
| (III) | 45583 | 3-bromo-4-(7-chloro-1H-inden-3-yl)-1-methyl-1H-pyrrole-2,5-dione | C14H9BrClNO2 | 详情 | 详情 | |
| (IV) | 45584 | bromo(1H-indol-1-yl)magnesium | C8H6BrMgN | 详情 | 详情 | |
| (V) | 45585 | 3-(7-chloro-1H-indol-3-yl)-4-(1H-indol-3-yl)-1-methyl-1H-pyrrole-2,5-dione | C21H14ClN3O2 | 详情 | 详情 | |
| (VI) | 45586 | (4bR,4cR,7aR,12bS)-1-chloro-6-methyl-7a,12,12b,13-tetrahydro-4bH-indolo[2,3-a]pyrrolo[3,4-c]carbazole-5,7(4cH,6H)-dione | 577-59-3 | C21H16ClN3O2 | 详情 | 详情 |
| (VII) | 45587 | 2-(trimethylsilyl)ethyl (3S,4S,6S)-4-hydroxy-6-[[(2R,3S,4R,5R,6R)-4,5,6-trihydroxy-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl(methyl)carbamate | C19H37NO10Si | 详情 | 详情 | |
| (VIII) | 45588 | 2-(trimethylsilyl)ethyl (3S,4S,6S)-6-[[(2R,3S,4R,5R,6R)-6-(11-chloro-6-methyl-5,7-dioxo-5,6,7,13-tetrahydro-12H-indolo[2,3-a]pyrrolo[3,4-c]carbazol-12-yl)-4,5-dihydroxy-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]-4-hydroxytetrahydro-2H-pyran-3-yl(methyl)carbamate | C40H47ClN4O11Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VII)The intermediate aminosugar (VII) has been obtained as follows: The protection of the alcohol (IX) with Bn-Br and NaH in DMF gives the benzyl ether (X), which is oxidized with OsO4 and NaIO4 in acetone/THF to yield the aldehyde (XI). The cyclization of (XI) by means of Ts-OH in dioxane/water affords the lactol (XII), which is treated with diethylamino sulfurtrifluoride (DAST) to provide the glycosyl fluoride (XIII). The condensation of (XIII) with the benzylated glucose derivative (XIV) by means of AgClO4 and SnCl2 in THF/ethyl ether gives the disaccharide (XV). The reduction of the carbamoyl group of (XV) with LiAlH4 in refluxing THF yields the methylamino derivative (XVI), which is protected at the methylamino group with trimethylsilylethyl(p-methylphenyl)carbonate (teoc-O-PNP) to afford the carbamate (XVII). Finally, this compound is debenzylated by hydrogenation over Pd/C in ethanol/THF to afford the target aminosugar (VIII).
| 【1】 Van Vranken, D.L.; Chisholm, J.D.; Regiocontrolled synthesis of the antitumor antibiotic AT2433-A1. J Org Chem 2000, 65, 22, 7541. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VII) | 45587 | 2-(trimethylsilyl)ethyl (3S,4S,6S)-4-hydroxy-6-[[(2R,3S,4R,5R,6R)-4,5,6-trihydroxy-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl(methyl)carbamate | C19H37NO10Si | 详情 | 详情 | |
| (IX) | 45589 | tert-butyl (4S)-4-(1-hydroxy-3-butenyl)-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C14H25NO4 | 详情 | 详情 | |
| (X) | 45590 | tert-butyl (4S)-4-[1-(benzyloxy)-3-butenyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | 15930-53-7 | C21H31NO4 | 详情 | 详情 |
| (XI) | 45591 | tert-butyl (4S)-4-[1-(benzyloxy)-3-oxopropyl]-2,2-dimethyl-1,3-oxazolidine-3-carboxylate | C20H29NO5 | 详情 | 详情 | |
| (XII) | 45592 | tert-butyl (3S,4S)-4-(benzyloxy)-6-hydroxytetrahydro-2H-pyran-3-ylcarbamate | C17H25NO5 | 详情 | 详情 | |
| (XIII) | 45593 | tert-butyl (3S,4S)-4-(benzyloxy)-6-fluorotetrahydro-2H-pyran-3-ylcarbamate | C17H24FNO4 | 详情 | 详情 | |
| (XIV) | 45594 | [(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methanol | C28H32O6 | 详情 | 详情 | |
| (XV) | 45595 | tert-butyl (3S,4S,6S)-4-(benzyloxy)-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-ylcarbamate | C45H55NO10 | 详情 | 详情 | |
| (XVI) | 45596 | N-((3S,4S,6S)-4-(benzyloxy)-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl)-N-methylamine; (3S,4S,6S)-4-(benzyloxy)-N-methyl-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-amine | C41H49NO8 | 详情 | 详情 | |
| (XVII) | 45597 | 2-(trimethylsilyl)ethyl (3S,4S,6S)-4-(benzyloxy)-6-[[(2R,3S,4S,5R,6R)-4,5,6-tris(benzyloxy)-3-methoxytetrahydro-2H-pyran-2-yl]methoxy]tetrahydro-2H-pyran-3-yl(methyl)carbamate | C47H61NO10Si | 详情 | 详情 |