|
【结 构 式】 
|
【分子编号】10747 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-2-[(benzyloxy)methoxy]-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 【CA登记号】 |
【 分 子 式 】C55H59NO15 【 分 子 量 】974.0712 【元素组成】C 67.82% H 6.11% N 1.44% O 24.64% |
合成路线1
该中间体在本合成路线中的序号：(VII)The benzoylation of (IV) with benzoyl chloride (V) and triethylamine in ethyl acetate affords the fully protected Taxol derivative (VI), which is desillylated with HF in acetonitrile giving the partially protected Taxol derivative (VII). Finally, this compound is fully deprotected by hydrogenation with H2 over Pd/C in isopropanal at 40 atm to give taxol.
| 【1】 Sisti, N.J.; Swindell, C.S.; Chander, M.C. (NaPro BioTherapeutics, Inc.); Paclitaxel synthesis from precursor compounds and methods of producing the same. US 5675025 . |
| 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 | |
| (V) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (VI) | 10746 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-2-[(benzyloxy)methoxy]-3-phenylpropanoyl]oxy)-1-hydroxy-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 | C61H73NO15Si | 详情 | 详情 | |
| (VII) | 10747 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-2-[(benzyloxy)methoxy]-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 | C55H59NO15 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IV)The hydrogenation of the protected taxol derivative (I) with H2 over Pd/C in aqueous THF gives the 3'-amino-2'-O-Bom protected taxol derivative (II), which is N-benzoylated by means of benzoyl anhydride (III) to provide the 2'-O-Bom protected taxol (IV). Finally this compound is deprotected by hydrogenation with H2 over Pd/C in THF/water in the presence of HCl or H2SO4 to afford the target paclitaxel.
| 【1】 McChesney, J.D.; Zygmunt, J. (NaPro BioTherapeutics, Inc.); Three-step conversion of protected taxane ester to paclitaxel. WO 0285879 . |
| 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) | 56876 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-({(2R,3S)-3-{[(benzyloxy)carbonyl]amino}-2-[(benzyloxy)methoxy]-3-phenylpropanoyl}oxy)-9-{[(benzyloxy)carbonyl]oxy}-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C64H67NO18 | 详情 | 详情 | |
| (II) | 56877 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-15-({(2R,3S)-3-amino-2-[(benzyloxy)methoxy]-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 | C48H55NO14 | 详情 | 详情 | |
| (III) | 56878 | 1-phenylvinyl benzoate | C15H12O2 | 详情 | 详情 | |
| (IV) | 10747 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-([(2R,3S)-3-(benzoylamino)-2-[(benzyloxy)methoxy]-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 | C55H59NO15 | 详情 | 详情 |