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【结 构 式】 
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【分子编号】28495 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-15-([(2R,3S)-3-[[(E,2Z)-2-methyl-2-butenylidene]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate 【CA登记号】 |
【 分 子 式 】C55H79NO12Si2 【 分 子 量 】1002.4028 【元素组成】C 65.9% H 7.94% N 1.4% O 19.15% Si 5.6% |
合成路线1
该中间体在本合成路线中的序号：(IVb)Several partial syntheses of docetaxel have been described: The selective hydrolysis of Taxol A (I, R = Ph), Taxol B (I, R = C(Me)=CHMe) or Taxol C (I, R = C5H11) with NaHCO3 in THF/water gives the corresponding 10-deacetyl derivatives (II), which by selective silylation with triethylsilyl chloride in pyridine are converted into the 10-deacetyl-2',7-bis(triethylsilyl) compounds (III). The reaction of compounds (III) with zirconocene chloride hydride [bis(cyclopentadienyl)zirconium chloride hydride] in THF afford the corresponding imino derivatives (IV), which, without isolation are hydrolyzed and desilylated by a treatment with concentrated aqueous HCl in ethanol giving 10-deacetyltaxolamine (V). Finally, this compound is acylated at the amino group by a treatment by di-tert-butyl dicarbonate and NaHCO3 in ethyl acetate/water.
| 【1】 Young, T.H. (Hauser, Inc.); Preparation of Taxol and docetaxel through primary amines. EP 0852581; WO 9623780 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 14346 | di(tert-butyl) malonate; Di-tert-butyl malonate | 541-16-2 | C11H20O4 | 详情 | 详情 | |
| (IIa) | 10470 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C45H49NO13 | 详情 | 详情 | |
| (Ia) | 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 |
| (Ib) | 10731 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9-dihydroxy-15-[((2R,3S)-2-hydroxy-3-[[(E)-2-methyl-2-butenoyl]amino]-3-phenylpropanoyl)oxy]-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C45H53NO14 | 详情 | 详情 | |
| (IIIa) | 12495 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C57H77NO13Si2 | 详情 | 详情 | |
| (IVa) | 12496 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-15-([(2R,3S)-3-phenyl-3-[[(E)-benzylidene]amino]-2-[(triethylsilyl)oxy]propanoyl]oxy)-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C57H77NO12Si2 | 详情 | 详情 | |
| (Ic) | 28490 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-[(cyclopentylcarbonyl)amino]-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 | C46H55NO14 | 详情 | 详情 | |
| (IIb) | 28491 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,9,12-trihydroxy-15-[((2R,3S)-2-hydroxy-3-[[(Z)-2-methyl-2-butenoyl]amino]-3-phenylpropanoyl)oxy]-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H51NO13 | 详情 | 详情 | |
| (IIc) | 28492 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(cyclopentylcarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C44H53NO13 | 详情 | 详情 | |
| (IIIb) | 28493 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-15-([(2R,3S)-3-[[(Z)-2-methyl-2-butenoyl]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C55H79NO13Si2 | 详情 | 详情 | |
| (IIIc) | 28494 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(cyclopentylcarbonyl)amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C56H81NO13Si2 | 详情 | 详情 | |
| (IVb) | 28495 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-15-([(2R,3S)-3-[[(E,2Z)-2-methyl-2-butenylidene]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C55H79NO12Si2 | 详情 | 详情 | |
| (IVc) | 28496 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[[(E)-cyclopentylmethylidene]amino]-3-phenyl-2-[(triethylsilyl)oxy]propanoyl]oxy)-1,12-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[(triethylsilyl)oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C56H81NO12Si2 | 详情 | 详情 | |
| (V) | 12497 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1,9,12-trihydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C38H45NO12 | 详情 | 详情 |