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【结 构 式】 
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【药物名称】L-759656 【化学名称】3-(1,1-Dimethylheptyl)-1-methoxy-6,6-dimethyl-9-methylene-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene 【CA登记号】 【 分 子 式 】C26H40O2 【 分 子 量 】384.6075 |
【开发单位】Merck Frosst (Originator) 【药理作用】Pharmacological Tools, Cannabinoid CB2 Agonists |
合成路线1
Nabilone (I) was converted to the methylene analogue (II). Then, methylation of phenol group provided the title compound.
| 【1】 Tremblay, N.; Labelle, M.; Rochette, C.; Dufresne, C.; Gallant, M.; Gareau, Y.; Metters, K.M.; Sawyer, N.; Slipetz, D.M.; Weech, P.K.; Structure activity relatioships of tetrahydrocannabibol analogues on human cannabinoid receptors. Bioorg Med Chem Lett 1996, 6, 2, 189. |
合成路线2
The cyclization of aldehyde (I) or verbenol (II) with resorcinol (III) by means of BF3 in dichloromethane gives the tetrahydrocannabiol analoge (IV) after column chromatography purification. The methylation of (IV) by means of methyl iodide and K2CO3 in refluxing DMF yields the methyl ether (V), which is treated with anhydrous ZnCl2 and HCl in chloroform affording the HCl adduct (VI). Finally, this compound is dehydrochlorinated to the target compound by means of potassium tricyclopentylcarbinolate (K-tcpc) in refluxing toluene.
| 【1】 Teshima, K.; et al.; J Org Chem 1971, 36, 5, 721. |
| 【2】 Tremblay, N.; Labelle, M.; Rochette, C.; Dufresne, C.; Gallant, M.; Gareau, Y.; Metters, K.M.; Sawyer, N.; Slipetz, D.M.; Weech, P.K.; Structure activity relatioships of tetrahydrocannabibol analogues on human cannabinoid receptors. Bioorg Med Chem Lett 1996, 6, 2, 189. |
| 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) | 34542 | (2E)-3,7-dimethyl-2,6-octadienal | 5392-40-5 | C10H16O | 详情 | 详情 |
| (II) | 34543 | 4,6,6-trimethylbicyclo[3.1.1]hept-3-en-2-ol | C10H16O | 详情 | 详情 | |
| (III) | 20233 | 5-(1,1-dimethylheptyl)-1,3-benzenediol | C15H24O2 | 详情 | 详情 | |
| (IV) | 31571 | 3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-ol | C25H38O2 | 详情 | 详情 | |
| (V) | 34544 | 3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromen-1-yl methyl ether; 3-(1,1-dimethylheptyl)-1-methoxy-6,6,9-trimethyl-6a,7,10,10a-tetrahydro-6H-benzo[c]chromene | C26H40O2 | 详情 | 详情 | |
| (VI) | 34545 | 9-chloro-3-(1,1-dimethylheptyl)-1-methoxy-6,6,9-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromene; 9-chloro-3-(1,1-dimethylheptyl)-6,6,9-trimethyl-6a,7,8,9,10,10a-hexahydro-6H-benzo[c]chromen-1-yl methyl ether | C26H41ClO2 | 详情 | 详情 |