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【结 构 式】 
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【分子编号】23894 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-azido-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl ben 【CA登记号】 |
【 分 子 式 】C44H45Cl6N3O16 【 分 子 量 】1084.56812 【元素组成】C 48.73% H 4.18% Cl 19.61% N 3.87% O 23.6% |
合成路线1
该中间体在本合成路线中的序号：(VII)A new synthesis of docetaxel has been developed: The stereoselective dihydroxylation of methyl cinnamate (I) by the Sharpless AD process gives the enantiopure diol (II), which was treated first with tosyl chloride/triethylamine and then with K2CO3 in DMF yielding epoxide (III). Hydrolysis of the ester group of (III) with LiOH in methanol/water affords the epoxy-acid (IV), which is coupled with 7,10-bis(2,2,2-trichloroethoxycarbonyl)-10-deacetylbaccatin III (V) by means of dicyclohexylcarbodiimide (CDD) and dimethylaminopyridine in hot toluene to give the ester (VI). Regioselective cleavage of the epoxide ring of (VI) with NaN3 in aqueous methanol yielded the azide derivative (VII), which was treated with triphenylphosphine in the presence of tert-butoxycarbonyl anhydride and K2CO3 in dichloromethane affording the tert-butoxycarbonylamino derivative (VIII). Finally, (VIII) was submitted to a reductive deprotection with zinc powder in acetic acid.
| 【1】 Harada, N.; Yamaguchi, T.; Hashiyama, T.; Ozaki, K.; Synthesis of taxoids 3. A novel and efficient method for preparation of taxoids employing cis-glycidic acid. Tetrahedron Lett 1998, 39, 5575. |
| 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) | 23888 | methyl (E)-3-phenyl-2-propenoate | 103-26-4 | C10H10O2 | 详情 | 详情 |
| (II) | 23889 | methyl (2S,3R)-2,3-dihydroxy-3-phenylpropanoate | C10H12O4 | 详情 | 详情 | |
| (III) | 23890 | methyl (2R,3R)-3-phenyl-2-oxiranecarboxylate | 99528-65-1 | C10H10O3 | 详情 | 详情 |
| (IV) | 23891 | (2R,3R)-3-phenyl-2-oxiranecarboxylic acid | C9H8O3 | 详情 | 详情 | |
| (V) | 23892 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C35H38Cl6O14 | 详情 | 详情 | |
| (VI) | 23893 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (2R,3R)-3-phenyl-2-oxiranecarboxylate | C44H44Cl6O16 | 详情 | 详情 | |
| (VII) | 23894 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-[[(2R,3S)-3-azido-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl ben | C44H45Cl6N3O16 | 详情 | 详情 | |
| (VIII) | 23895 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4-(acetoxy)-15-([(2R,3S)-3-[(tert-butoxycarbonyl)amino]-2-hydroxy-3-phenylpropanoyl]oxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9,12-bis[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)] | C49H55Cl6NO18 | 详情 | 详情 |