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【结 构 式】 
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【分子编号】49239 【品名】(1S,6R,9S,12R)-12-methoxy-6-methyl-9-(4-vinylphenyl)-10,11,13-trioxatricyclo[7.2.2.0(1,6)]tridecane; methyl (1S,6R,9S,12R)-6-methyl-9-(4-vinylphenyl)-10,11,13-trioxatricyclo[7.2.2.0(1,6)]tridec-12-yl ether 【CA登记号】 |
【 分 子 式 】C20H26O4 【 分 子 量 】330.42404 【元素组成】C 72.7% H 7.93% O 19.37% |
合成路线1
该中间体在本合成路线中的序号：(VIII)The reaction of cyclohexanone (I) with acrylonitrile (II) by means of pyrrolidine gives 3-(2-oxocyclohexyl)propionitrile (III), which is condensed with methoxymethyltriphenylphosphonium chloride (IV) in THF to yield the methoxymethylene derivative (V). The condensation of propionitrile (V) with 4-bromostyrene (VI) by means of n-BuLi ethyl ether affords the styryl ketone (VII), which is cyclized by means of triphenyl phosphite and O3 (or air, methylene blue and light) to provide trioxane (VIII) as a diastereomeric mixture that is separated by column chromatography. Finally, the vinyl group of the desired diastereomer (VIII) is oxidized with KMnO4 in acetone to afford the target compound.
| 【1】 Parker, M.H.; Krasavin, M.; Posner, G.H.; Paik, I.-H.; Jeon, H.B.; Shapiro, T.A.; Antimalarial simplified 3-aryltrioxanes: Synthesis and preclinical efficacy/toxicity testing in rodents. J Med Chem 2001, 44, 19, 3054. |
| 【2】 Posner, G.H.; Shapiro, T.A.; Parker, M.H.; Krasavin, M. (Johns Hopkins University); Water-soluble trioxanes as potent and safe antimalarial agents. US 6136847; WO 0059501 . |
| 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) | 11059 | Cyclohexanone | 108-94-1 | C6H10O | 详情 | 详情 |
| (II) | 10847 | Acrylonitrile | 107-13-1 | C3H3N | 详情 | 详情 |
| (III) | 49235 | 2-(beta-Cyanoethyl)cyclohexanone | C9H13NO | 详情 | 详情 | |
| (IV) | 39163 | (methoxymethyl)(triphenyl)phosphonium chloride | 4009-98-7 | C20H20ClOP | 详情 | 详情 |
| (V) | 49236 | 3-[2-[(Z)-methoxymethylidene]cyclohexyl]propanenitrile | C11H17NO | 详情 | 详情 | |
| (VI) | 49237 | 4-Bromostyrene; p-Bromostyrene | 2039-82-9 | C8H7Br | 详情 | 详情 |
| (VII) | 49238 | 3-[2-[(Z)-methoxymethylidene]cyclohexyl]-1-(4-vinylphenyl)-1-propanone | C19H24O2 | 详情 | 详情 | |
| (VIII) | 49239 | (1S,6R,9S,12R)-12-methoxy-6-methyl-9-(4-vinylphenyl)-10,11,13-trioxatricyclo[7.2.2.0(1,6)]tridecane; methyl (1S,6R,9S,12R)-6-methyl-9-(4-vinylphenyl)-10,11,13-trioxatricyclo[7.2.2.0(1,6)]tridec-12-yl ether | C20H26O4 | 详情 | 详情 |