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【结 构 式】 
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【药物名称】Chackol 【化学名称】Benzoic acid (2aR,4S,4aS,6R,9S,11S,12S,12aR,12bS)-6,12b-diacetoxy-9-[3(S)-benzamido-2(R)-[3-[N-[4-oxo-4-(D-glucopyranosyloxy)butyl]carbamoyl]propionyloxy]-3-phenylpropionyloxy]-4,11-dihydroxy-4a,8,13,13-tetramethyl-5-oxo-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benzo[1,2-b]oxet-12-yl ester 【CA登记号】 【 分 子 式 】C61H72N2O23 【 分 子 量 】1201.25359 |
【开发单位】Organomed (Originator) 【药理作用】Oncolytic Drugs, Taxanes |
合成路线1
Esterification of glucose diacetonide (I) with N-Boc-gamma-aminobutyric acid (II) in the presence of DCC and DMAP provides the protected glucose-3-ester (III). Hydrolysis of (III) with trifluoroacetic acid in CH2Cl2 leads to the 3-GABA-glucose (IV).
| 【1】 Jacob, J.N. (Organomed Corporation); Paclitaxel-carbohydrate conjugates: Design, synthesis and biological evaluations. US 6218367 . |
| 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) | 59011 | (5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol | C12H20O6 | 详情 | 详情 | |
| (II) | 39226 | 4-[(tert-butoxycarbonyl)amino]butyric acid;4-((tert-butoxycarbonyl)amino)butanoic acid | 57294-38-9 | C9H17NO4 | 详情 | 详情 |
| (III) | 59012 | (5S,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl 4-[(tert-butoxycarbonyl)amino]butanoate | C21H35NO9 | 详情 | 详情 | |
| (IV) | 59013 | (3R,4S,5R,6R)-2,3,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl 4-aminobutanoate | C10H19NO7 | 详情 | 详情 |
合成路线2
Condensation of paclitaxel (V) with succinic anhydride (VI) affords the hemisuccinate ester (VII). This is subsequently coupled with amino ester (IV) in the presence of DCC to furnish the title compound.
| 【1】 Jacob, J.N. (Organomed Corporation); Paclitaxel-carbohydrate conjugates: Design, synthesis and biological evaluations. US 6218367 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IV) | 59013 | (3R,4S,5R,6R)-2,3,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl 4-aminobutanoate | C10H19NO7 | 详情 | 详情 | |
| (V) | 10595 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | 33069-62-4 | C47H51NO14 | 详情 | 详情 |
| (VI) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |
| (VII) | 59014 | 4-{[(1R,2S)-2-(benzoylamino)-1-({[(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1,9-dihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-15-yl]oxy}carbonyl)-2-phenylethyl]oxy}-4-oxobutano | C51H55NO17 | 详情 | 详情 |