【结 构 式】 |
【分子编号】10731 【品名】(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 【CA登记号】 |
【 分 子 式 】C45H53NO14 【 分 子 量 】831.91416 【元素组成】C 64.97% H 6.42% N 1.68% O 26.92% |
合成路线1
该中间体在本合成路线中的序号:(VI)2) The silylation of Taxol B (VI) with triethylsilyl chloride as before gives the bis(triethylsilyl) compound (VII), which by reduction with zirconocene chloride hydride as described yields compound (VIII). Finally, the hydrolytic cleavage of (VIII) with simultaneous desilylation with HCl in ethanol affords the previously reported compound (IV) with its free amino group easily benzoylated to Taxol. 3) The ozonolysis of the silylated Taxol B (VII) with O3 in methanol gives compound (IX), which is reduced with zirconocene as before yielding the 2-oxopropylideneimine (X). Finally, the hydrolytic cleavage of (X) with simultaneous desilylation with HCl in ethanol affords the previously reported compound (IX) with its free amino group easiely benzoylated to Taxol.
【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 |
---|---|---|---|---|---|---|
(IV) | 10729 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-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 | C40H47NO13 | 详情 | 详情 | |
(VI) | 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 | |
(VII) | 10732 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-15-([(2R,3S)-3-[[(E)-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 | C57H81NO14Si2 | 详情 | 详情 | |
(VIII) | 10733 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9-dihydroxy-15-[((2R,3S)-2-hydroxy-3-[[(E,2E)-2-methyl-2-butenylidene]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 | C45H53NO13 | 详情 | 详情 | |
(IX) | 10734 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-([(2R,3S)-3-phenyl-3-(pyruvoylamino)-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 | C55H77NO15Si2 | 详情 | 详情 | |
(X) | 10735 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-15-([(2R,3S)-3-[[(E)-2-oxopropylidene]amino]-3-phenyl-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 | C55H77NO14Si2 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号:(Ib)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 |