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【结 构 式】 
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【分子编号】32011 【品名】(1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-9-[(tert-butoxycarbonyl)oxy]-1,15-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 】C36H46O13 【 分 子 量 】686.75344 【元素组成】C 62.96% H 6.75% O 30.29% |
合成路线1
该中间体在本合成路线中的序号：(VII)3) The selective protection of baccatin III (I) with tert-butoxycarbonyl anhydride and Li-HMDS in DMF gives 7-O-(tert-butoxycarbonyl)baccatin III (VII), which is condensed with the chiral oxazolidine (III) by means of DCC and DMAP in toluene affording the 13-O-oxazolidinyl derivative (VIII). Finally, this compound is deprotected with formic or acetic acids, and the oxazolidine ring is cleaved with trifluoroacetic acid/acetic acid.
| 【1】 Gibson, F.S. (Bristol-Myers Squibb Co.); Synthesis of paclitaxel baccatin III by protecting the 7-hydroxyl using a strong base and an electrophile. WO 9945001 . |
| 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) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-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 | C31H38O11 | 详情 | 详情 | |
| (III) | 10597 | (4S,5R)-2,4-Diphenyl-4,5-dihydro-1,3-oxazole-5-carboxylic acid | C16H13NO3 | 详情 | 详情 | |
| (VII) | 32011 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-9-[(tert-butoxycarbonyl)oxy]-1,15-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 | C36H46O13 | 详情 | 详情 | |
| (VIII) | 32012 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-2-(benzoyloxy)-9-[(tert-butoxycarbonyl)oxy]-1-hydroxy-10,14,17,17-tetramethyl-11-oxo-6-oxatetracyclo[11.3.1.0(3,10).0(4,7)]heptadec-13-en-15-yl (4S,5R)-2,4-diphenyl-4,5-dihydro-1,3-oxazole-5-carbox | C52H57NO15 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)5) The selective protection of baccatin III (I) with benzyloxycarbonyl anhydride and Li-HMDS in DMF gives 7-O-(benzyloxycarbonyl)baccatin III (V), which is condensed with the chiral azetidinone (IX) by means of lithium tert-butoxide or Li-HMDS in THF and the reaction product, without isolation, is treated with trifluoroacetic acid and acetic acid to afford the protected taxol derivative (XI). Finally, this compound is deprotected by hydrogenation with H2 over Pd/C in ethanol.
| 【1】 Gibson, F.S. (Bristol-Myers Squibb Co.); Synthesis of paclitaxel baccatin III by protecting the 7-hydroxyl using a strong base and an electrophile. WO 9945001 . |
| 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) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-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 | C31H38O11 | 详情 | 详情 | |
| (V) | 32009 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-9-[[(benzyloxy)carbonyl]oxy]-1,15-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 | C39H44O13 | 详情 | 详情 | |
| (IX) | 32011 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-9-[(tert-butoxycarbonyl)oxy]-1,15-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 | C36H46O13 | 详情 | 详情 | |
| (XI) | 32016 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-15-[[(2R,3S)-3-(benzoylamino)-2-hydroxy-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 benzoa | C55H57NO16 | 详情 | 详情 |
合成路线3
该中间体在本合成路线中的序号：(VII)6) The selective protection of baccatin III (I) with tert-butoxycarbonyl anhydride and Li-HMDS in DMF gives 7-O-(tert-butoxycarbonyl)baccatin III (VII), which is condensed with the chiral azetidinone (IX) by means of lithium tert-butoxide or Li-HMDS in THF and the reaction product, without isolation, is treated with trifluoroacetic acid and acetic acid.
| 【1】 Gibson, F.S. (Bristol-Myers Squibb Co.); Synthesis of paclitaxel baccatin III by protecting the 7-hydroxyl using a strong base and an electrophile. WO 9945001 . |
| 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) | 10447 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-1,9,15-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 | C31H38O11 | 详情 | 详情 | |
| (VII) | 32011 | (1S,2S,3R,4S,7R,9S,10S,12R,15S)-4,12-bis(acetoxy)-9-[(tert-butoxycarbonyl)oxy]-1,15-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 | C36H46O13 | 详情 | 详情 | |
| (IX) | 32014 | (3R,4S)-1-benzoyl-3-(1-methoxy-1-methylethoxy)-4-phenyl-2-azetidinone | C20H21NO4 | 详情 | 详情 |