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【结 构 式】 
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【分子编号】38192 【品名】4-hydroxy-7-([(7R,8R,9R,10R)-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-9-[(triethylsilyl)oxy]-6-oxaspiro[4.5]dec-7-yl]oxy)-8-methyl-2H-chromen-2-one 【CA登记号】 |
【 分 子 式 】C31H46O9Si 【 分 子 量 】590.78634 【元素组成】C 63.02% H 7.85% O 24.37% Si 4.75% |
合成路线1
该中间体在本合成路线中的序号：(XII)Grignard reagent (II), prepared from 1,4-dibromobutane (I), was added to lactone (III) to produce the cyclopentanol derivative (IV). Oxidation of the primary alcohol of (IV) with sulfur trioxide-pyridine complex in the presence of DMSO gave rise to lactone (V), which was reduced to the corresponding lactol (VI) by means of DIBAL at low temperature. Subsequent acid hydrolysis of the ketal group of (VI) afforded triol (VII). Mitsunobu coupling with 4-(diphenylmethoxy)-7-hydroxycoumarin (VIII) furnished ether (IX). After selective hydroxyl group protection of (IX) with chlorotriethylsilane to give (X), the remaining free hydroxyl was further protected as the tetrahydropyranyl ether (XI). Then, removal of the benzhydryl protecting group of (XI) was achieved by hydrogenation over Pd/C to give (XII).
| 【1】 Periers, A.-M.; Laurin, P.; Klich, M.; Musicki, B.; Haesslein, J.-L. (Aventis Pharma SA); Novel aromatic amides, preparation method and application as medicines. FR 2773369; WO 9935155 . |
| 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) | 11883 | 1,4-Dibromobutane; 1,4-Butylene bromide | 110-52-1 | C4H8Br2 | 详情 | 详情 |
| (II) | 38182 | 1,4-Bis(bromomagnesio)butane | 23708-48-7 | C4H8Br2Mg2 | 详情 | 详情 |
| (III) | 38183 | (3aS,7R,7aR)-7-methoxy-2,2-dimethyltetrahydro-6H-[1,3]dioxolo[4,5-c]pyran-6-one | C9H14O5 | 详情 | 详情 | |
| (IV) | 38184 | 1-[(R)-[(4R,5S)-5-(hydroxymethyl)-2,2-dimethyl-1,3-dioxolan-4-yl](methoxy)methyl]cyclopentanol | C13H24O5 | 详情 | 详情 | |
| (V) | 38185 | C13H20O5 | 详情 | 详情 | ||
| (VI) | 38186 | C13H22O5 | 详情 | 详情 | ||
| (VII) | 38187 | (8R,9S,10R)-10-methoxy-6-oxaspiro[4.5]decane-7,8,9-triol | C10H18O5 | 详情 | 详情 | |
| (VIII) | 38188 | 4-(benzhydryloxy)-7-hydroxy-8-methyl-2H-chromen-2-one | C23H18O4 | 详情 | 详情 | |
| (IX) | 38189 | 4-(benzhydryloxy)-7-[[(7R,8R,9S,10R)-8,9-dihydroxy-10-methoxy-6-oxaspiro[4.5]dec-7-yl]oxy]-8-methyl-2H-chromen-2-one | C33H34O8 | 详情 | 详情 | |
| (X) | 38190 | 4-(benzhydryloxy)-7-([(7R,8R,9S,10R)-8-hydroxy-10-methoxy-9-[(triethylsilyl)oxy]-6-oxaspiro[4.5]dec-7-yl]oxy)-8-methyl-2H-chromen-2-one | C39H48O8Si | 详情 | 详情 | |
| (XI) | 38191 | 4-(benzhydryloxy)-7-([(7R,8R,9R,10R)-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-9-[(triethylsilyl)oxy]-6-oxaspiro[4.5]dec-7-yl]oxy)-8-methyl-2H-chromen-2-one | C44H56O9Si | 详情 | 详情 | |
| (XII) | 38192 | 4-hydroxy-7-([(7R,8R,9R,10R)-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-9-[(triethylsilyl)oxy]-6-oxaspiro[4.5]dec-7-yl]oxy)-8-methyl-2H-chromen-2-one | C31H46O9Si | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(XII)Acylation of (XII) with acetic anhydride and DMAP yielded the 3-acetyl coumarin (XIII). Following desilylation of (XIII) with tetrabutylammonium fluoride to give (XIV), condensation with O-methyl hydroxylamine gave oxime (XV). Treatment of (XV) with p-nitrophenyl chloroformate and DMAP generated carbonate (XVI), which was further coupled with O-propargyl hydroxylamine (XVII) to yield carbamate (XVIII). The tetrahydropyranyl group of (XVIII) was finally deprotected by methanolysis in the presence of p-toluenesulfonic acid.
| 【1】 Periers, A.-M.; Laurin, P.; Klich, M.; Musicki, B.; Haesslein, J.-L. (Aventis Pharma SA); Novel aromatic amides, preparation method and application as medicines. FR 2773369; WO 9935155 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 | |
| (XII) | 38192 | 4-hydroxy-7-([(7R,8R,9R,10R)-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-9-[(triethylsilyl)oxy]-6-oxaspiro[4.5]dec-7-yl]oxy)-8-methyl-2H-chromen-2-one | C31H46O9Si | 详情 | 详情 | |
| (XIII) | 38193 | 3-acetyl-4-hydroxy-7-([(7R,8R,9R,10R)-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-9-[(triethylsilyl)oxy]-6-oxaspiro[4.5]dec-7-yl]oxy)-8-methyl-2H-chromen-2-one | C33H48O10Si | 详情 | 详情 | |
| (XIV) | 38194 | 3-acetyl-4-hydroxy-7-[[(7R,8R,9R,10R)-9-hydroxy-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-6-oxaspiro[4.5]dec-7-yl]oxy]-8-methyl-2H-chromen-2-one | C27H34O10 | 详情 | 详情 | |
| (XV) | 38195 | 3-ethanimidoyl-4-hydroxy-7-[[(7R,8R,9R,10R)-9-hydroxy-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-6-oxaspiro[4.5]dec-7-yl]oxy]-8-methyl-2H-chromen-2-one | C28H37NO10 | 详情 | 详情 | |
| (XVI) | 38196 | (7R,8R,9R,10R)-7-[(3-ethanimidoyl-4-hydroxy-8-methyl-2-oxo-2H-chromen-7-yl)oxy]-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-6-oxaspiro[4.5]dec-9-yl 4-nitrophenyl carbonate | C35H40N2O14 | 详情 | 详情 | |
| (XVII) | 38197 | O-(2-propynyl)hydroxylamine; 3-(aminooxy)-1-propyne | C3H5NO | 详情 | 详情 | |
| (XVIII) | 38198 | (7R,8R,9R,10R)-7-[(3-ethanimidoyl-4-hydroxy-8-methyl-2-oxo-2H-chromen-7-yl)oxy]-10-methoxy-8-(tetrahydro-2H-pyran-2-yloxy)-6-oxaspiro[4.5]dec-9-yl 2-propynyloxycarbamate | C32H40N2O12 | 详情 | 详情 |