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【结 构 式】 
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【分子编号】64028 【品名】(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-(2-{[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]methyl}-2-propenyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecane 【CA登记号】 |
【 分 子 式 】C34H52O8 【 分 子 量 】588.78208 【元素组成】C 69.36% H 8.9% O 21.74% |
合成路线1
该中间体在本合成路线中的序号：(VI)Reduction of artemisinin (I) with DIBAL, followed by acetylation of the resultant lactol (II) with Ac2O/DMAP leads to dihydroartemisinin acetate (III). Treatment of the allylic dichloride (IV) with trimethylsilyllithium provides the bis-silane derivative (V). Then, coupling of dihydroartemisinin acetate (III) with bis-silane (V) in the presence of SnCl4 gives rise to the artemisinin dimer (VI).
| 【1】 Posner, G.H.; Paik, I.-P.; Sur, S.; McRiner, A.J.; Borstnik, K.; Zie, S.; Shapiro, T.A.; Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy. J Med Chem 2003, 46, 6, 1060. |
| 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) | 22369 | Qinghaosu; Artemisine; (1R,4S,5R,8S,9R,12S,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadecan-10-one | 63968-64-9 | C15H22O5 | 详情 | 详情 |
| (II) | 22370 | Dihydroartemisinin; (1R,4S,5R,8S,9R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0(4,13).0(8,13)]hexadecan-10-ol | C15H24O5 | 详情 | 详情 | |
| (III) | 56087 | (1R,4S,5R,8S,9R,10S,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl acetate | C17H26O6 | 详情 | 详情 | |
| (IV) | 64026 | 3-chloro-2-(chloromethyl)-1-propene | C4H6Cl2 | 详情 | 详情 | |
| (V) | 64027 | trimethyl{2-[(trimethylsilyl)methyl]-2-propenyl}silane | C10H24Si2 | 详情 | 详情 | |
| (VI) | 64028 | (1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-(2-{[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]methyl}-2-propenyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecane | C34H52O8 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(VI)Hydroboration of the double bond of (VI), followed by quenching with NaBO3 yields the primary alcohol (VII). This is then acylated by succinic anhydride (VIII) in the presence of DMAP to provide the target succinate ester.
| 【1】 Posner, G.H.; Paik, I.-P.; Sur, S.; McRiner, A.J.; Borstnik, K.; Zie, S.; Shapiro, T.A.; Orally active, antimalarial, anticancer, artemisinin-derived trioxane dimers with high stability and efficacy. J Med Chem 2003, 46, 6, 1060. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (VI) | 64028 | (1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-10-(2-{[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]methyl}-2-propenyl)-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadecane | C34H52O8 | 详情 | 详情 | |
| (VII) | 64030 | 3-[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]-2-{[(1R,4S,5R,8S,9R,10R,12R,13R)-1,5,9-trimethyl-11,14,15,16-tetraoxatetracyclo[10.3.1.0~4,13~.0~8,13~]hexadec-10-yl]methyl}-1-propanol | C34H54O9 | 详情 | 详情 | |
| (VIII) | 11291 | Dihydro-2,5-furandione; Succinic anhydride | 108-30-5 | C4H4O3 | 详情 | 详情 |