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【结 构 式】 
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【分子编号】55696 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-15-{[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}-1,4-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]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 】C48H50Cl3NO15 【 分 子 量 】987.28084 【元素组成】C 58.4% H 5.1% Cl 10.77% N 1.42% O 24.31% |
合成路线1
该中间体在本合成路线中的序号：(XII)The reaction of (2R,3S)-phenylisoserine (I) with 2-propynyl chloroformate (II) in aq. NaHCO3 gives the N-acylated compound (III), which is treated with diazomethane in ethyl ether (CDI and methanol) to yield the corresponding methyl ester (IV). The reaction of (IV) with 2-methoxypropene (V) and pyridinium p-toluenesulfonate in toluene affords the oxazolidine (VI), which is treated with LiOH in water to provide the oxazolidine-5-carboxylic acid (VII). The esterification of 7-O-(trichloroethoxycarbonyl)baccatin (VIII) with acid (VII) by means of DCC in toluene gives the corresponding ester (IX), which is treated with ammonium tetrathiomolybdate to cleave the oxazolidine ring and yield the 3-amino-2-hydroxypropionyl ester (X). The reaction of (X) with benzoyl chloride (XI) and NaHCO3 in ethyl acetate affords the expected benzamido derivative (XII), which is finally deprotected by means of Zn and AcOH to afford the target paclitaxel.
| 【1】 Sharma, A.P.; Sarkar, S. (Dabur India Ltd.); Method of preparation of paclitaxel (Taxol) using 3-(alk-2-ynyloxy)carbonyl-5-oxazolidine carboxylic acid. WO 0266448 . |
| 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) | 54908 | (2R,3S)-3-amino-2-hydroxy-3-phenylpropanoic acid | 136561-53-0 | C9H11NO3 | 详情 | 详情 |
| (II) | 55690 | Propargyl chloroformate | C4H3ClO2 | 详情 | 详情 | |
| (III) | 55691 | (2R,3S)-2-hydroxy-3-phenyl-3-{[(2-propynyloxy)carbonyl]amino}propanoic acid | C13H13NO5 | 详情 | 详情 | |
| (IV) | 55692 | methyl (2R,3S)-2-hydroxy-3-phenyl-3-{[(2-propynyloxy)carbonyl]amino}propanoate | C14H15NO5 | 详情 | 详情 | |
| (V) | 17354 | isopropenyl methyl ether; 2-methoxy-1-propene | 116-11-0 | C4H8O | 详情 | 详情 |
| (VI) | 55693 | 5-methyl 3-(2-propynyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate | C17H19NO5 | 详情 | 详情 | |
| (VII) | 55694 | (4S,5R)-2,2-dimethyl-4-phenyl-3-[(2-propynyloxy)carbonyl]-1,3-oxazolidine-5-carboxylic acid | C16H17NO5 | 详情 | 详情 | |
| (VIII) | 10448 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,15-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C34H39Cl3O13 | 详情 | 详情 | |
| (IX) | 55695 | 5-((1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetyloxy)-2-(benzoyloxy)-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-15-yl) 3-(2-propynyl) (4S,5R)-2,2-dimethyl-4-phenyl-1,3-oxazolidine-3,5-dicarboxylate | C50H54Cl3NO17 | 详情 | 详情 | |
| (X) | 10554 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-amino-2-hydroxy-3-phenylpropanoyl]oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-9-[[(2,2,2-trichloroethoxy)carbonyl]oxy]-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C43H48Cl3NO15 | 详情 | 详情 | |
| (XI) | 10463 | Benzoyl chloride | 98-88-4 | C7H5ClO | 详情 | 详情 |
| (XII) | 55696 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-12-(acetyloxy)-15-{[(2R,3S)-3-(benzoylamino)-2-hydroxy-3-phenylpropanoyl]oxy}-1,4-dihydroxy-10,14,17,17-tetramethyl-11-oxo-9-{[(2,2,2-trichloroethoxy)carbonyl]oxy}-6-oxatetracyclo[11.3.1.0~3,10~.0~4,7~]heptadec-13-en-2-yl benzoate | C48H50Cl3NO15 | 详情 | 详情 |