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【结 构 式】 
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【分子编号】10672 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-(2-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-(methoxymethoxy)-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 】C55H65NO17 【 分 子 量 】1012.11764 【元素组成】C 65.27% H 6.47% N 1.38% O 26.87% |
合成路线1
该中间体在本合成路线中的序号：(LV)The stereoselective reduction of the lesshindered ketonic group of (II) followed by benzoylation yields the polycyclic ketone (L), which is submitted to an allylic oxidation to afford the unsaturated dione (LI). The sequential selective reduction of the less hindered ketone with a bulky borohydride gives an alpha-alcohol, which is then benzylated with benzyl chloride and finally treated with H2 and Raney Nickel to eliminate the dithiane group and afford the polycyclic ketone (LII). The regioselective Franklin Davis hydroxylation of (LII) followed by desilylation with TBAF and peracetylation with acetic anhydride yields the triacetoxy ketone (LIII), which is debenzylated by hydrogenation with H2 over Pd/C to the secondary alcohol (LIV). The attachment of the propenoyl side-chain of paclitaxel to (LIV) according to J Amer Chem Soc 1988, 110: 5917 gives the protected paclitaxel derivative (LV), which is submitted to a selective deacetylation to the paclitaxel precursor (LVI). Finally, this compound is deprotected to paclitaxel.
| 【1】 Danishefsky, S.J.; Bornmann, W.G.; Queneau, Y.; Magee, T.V.; Krol, W.J. (Sloan-Kettering Institute); Total synthesis of taxol. US 5416225 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (IL) | 10666 | (2aR,4S,11S,12aR,12bS)-11-(Methoxymethyl)-4a,8,13,13-tetramethyl-4,12b-bis(tert-butyldimethylsilyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxete-5,6,12-trione 6,6-propyleneditihoketal | C37H64O7S2Si2 | 详情 | 详情 | |
| (L) | 10667 | (2aR,4S,11S,12S,12aR,12bS)-12-(Benzoyloxy)-11-(methoxymethyl)-4a,8,13,13-tetramethyl-4,12b-bis(tert-butyldimethylsilyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxete-5,6-dione 6,6-propyleneditihoketal | C44H70O8S2Si2 | 详情 | 详情 | |
| (LI) | 10668 | (2aR,4S,11S,12S,12aR,12bS)-12-(Benzoyloxy)-11-(methoxymethyl)-4a,8,13,13-tetramethyl-4,12b-bis(tert-butyldimethylsilyloxy)-2a,3,4,4a,5,6,9,10,11,12,12a,12b-dodecahydro-1H-7,11-methanocyclodeca[3,4]benz[1,2-b]oxete-5,6,9-trione 6,6-propyleneditihoketal | C44H68O9S2Si2 | 详情 | 详情 | |
| (LII) | 10669 | (1S,2S,3R,4S,7R,9S,10S,15S)-15-(benzyloxy)-4,9-bis[[tert-butyl(dimethyl)silyl]oxy]-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C48H72O9Si2 | 详情 | 详情 | |
| (LIII) | 10670 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetoxy)-15-(benzyloxy)-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C42H50O13 | 详情 | 详情 | |
| (LIV) | 10671 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetoxy)-15-hydroxy-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C35H44O13 | 详情 | 详情 | |
| (LV) | 10672 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,9,12-tris(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-(2-ethoxyethoxy)-3-phenylpropanoyl]oxy]-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C55H65NO17 | 详情 | 详情 | |
| (LVI) | 10673 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-(2-ethoxyethoxy)-3-phenylpropanoyl]oxy]-9-hydroxy-1-(methoxymethoxy)-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-2-yl benzoate | C53H63NO16 | 详情 | 详情 |