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【结 构 式】 
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【分子编号】35411 【品名】5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-isopropoxy-3-methyl-1-naphthol 【CA登记号】 |
【 分 子 式 】C38H47NO4 【 分 子 量 】581.79552 【元素组成】C 78.45% H 8.14% N 2.41% O 11% |
合成路线1
该中间体在本合成路线中的序号：(XIII)Further intramolecular Friedel-Crafts acylation in boiling acetic anhydride gave rise to naphthalene (XI). Reduction of the ethyl ester group of (XI) with LiAlH4 also produced the reductive cleavage of the phenolic acetate to furnish diol (XII). Conversion of the hydroxymethyl group of (XII) into the required methyl group was achieved by chlorination upon treatment with dibromotetrachloroethane and triphenylphosphine, followed by reductive dehalogenation to the methyl analogue (XIII) with LiAlH4. The free hydroxyl group of (XIII) was then methylated with dimethyl sulfate using phase-transfer catalysis to provide methyl ether (XIV), which was treated with BCl3 in order to eliminate the isopropyl protecting groups yielding the trihydroxy derivative (XV). Finally, hydrogenolysis of the N-benzyl protecting group of (XV) over Pd/C yielded the title compound.
| 【1】 Bringmann, G.; et al.; First atropo-divergent total synthesis of the antimalarial korupensamines A and B by the "lactone method". J Org Chem 2000, 65, 7, 2069. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 35408 | (E)-4-[2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxyphenyl]-3-(ethoxycarbonyl)-3-butenoic acid | C40H51NO7 | 详情 | 详情 | |
| (XI) | 35409 | ethyl 4-(acetoxy)-8-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxy-2-naphthoate | C42H51NO7 | 详情 | 详情 | |
| (XII) | 35410 | 5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-3-(hydroxymethyl)-8-isopropoxy-1-naphthol | C38H47NO5 | 详情 | 详情 | |
| (XIII) | 35411 | 5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-isopropoxy-3-methyl-1-naphthol | C38H47NO4 | 详情 | 详情 | |
| (XIV) | 35412 | 5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-isopropoxy-3-methyl-1-naphthyl methyl ether; (1R,3R)-2-benzyl-6,8-diisopropoxy-5-(4-isopropoxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C39H49NO4 | 详情 | 详情 | |
| (XV) | 35413 | (1R,3R)-2-benzyl-5-(4-hydroxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol | C30H31NO4 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XIII)Further intramolecular Friedel-Crafts acylation in boiling acetic anhydride gave rise to naphthalene (XI). Reduction of the ethyl ester group of (XI) with LiAlH4 also produced the reductive cleavage of the phenolic acetate to furnish diol (XII). Conversion of the hydroxymethyl group of (XII) into the required methyl group was achieved by chlorination upon treatment with dibromotetrachloroethane and triphenylphosphine, followed by reductive dehalogenation to the methyl analogue (XIII) with LiAlH4. The free hydroxyl group of (XIII) was then methylated with dimethyl sulfate using phase-transfer catalysis to provide methyl ether (XIV), which was treated with BCl3 in order to eliminate the isopropyl protecting groups yielding the trihydroxy derivative (XV). Finally, hydrogenolysis of the N-benzyl protecting group of (XV) over Pd/C yielded the title compound.
| 【1】 Bringmann, G.; et al.; First atropo-divergent total synthesis of the antimalarial korupensamines A and B by the "lactone method". J Org Chem 2000, 65, 7, 2069. |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| (X) | 35408 | (E)-4-[2-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxyphenyl]-3-(ethoxycarbonyl)-3-butenoic acid | C40H51NO7 | 详情 | 详情 | |
| (XI) | 35409 | ethyl 4-(acetoxy)-8-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-5-isopropoxy-2-naphthoate | C42H51NO7 | 详情 | 详情 | |
| (XII) | 35410 | 5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-3-(hydroxymethyl)-8-isopropoxy-1-naphthol | C38H47NO5 | 详情 | 详情 | |
| (XIII) | 35411 | 5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-isopropoxy-3-methyl-1-naphthol | C38H47NO4 | 详情 | 详情 | |
| (XIV) | 35412 | 5-[(1R,3R)-2-benzyl-6,8-diisopropoxy-1,3-dimethyl-1,2,3,4-tetrahydro-5-isoquinolinyl]-8-isopropoxy-3-methyl-1-naphthyl methyl ether; (1R,3R)-2-benzyl-6,8-diisopropoxy-5-(4-isopropoxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydroisoquinoline | C39H49NO4 | 详情 | 详情 | |
| (XV) | 35413 | (1R,3R)-2-benzyl-5-(4-hydroxy-5-methoxy-7-methyl-1-naphthyl)-1,3-dimethyl-1,2,3,4-tetrahydro-6,8-isoquinolinediol | C30H31NO4 | 详情 | 详情 |