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【结 构 式】 
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【分子编号】44367 【品名】4-hydroxy-4-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-1-butanone 【CA登记号】 |
【 分 子 式 】C24H32O9S 【 分 子 量 】496.57868 【元素组成】C 58.05% H 6.5% O 29% S 6.46% |
合成路线1
该中间体在本合成路线中的序号：(VII)The reaction of 3,4,5-trimethoxyacetophenone (I) with diethylamine and formaldehyde gives 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)-1-propanone (II), which is treated with methyl iodide at 80 C to yield 1-(3,4,5-trimethoxyphenyl)-2-propen-1-one (III). The condensation of (III) with 3-methoxy-5-(methylsulfonyl)-4-propoxybenzaldehyde (IV) by means of TEA and the thiazolium derivative (V) affords the asymmetric butane-1,4-dione (VI), which is reduced with LiAlH4 or NaBH4 to provide the (RS,RS)-butane-1,4-diol (VIII). Finally, this compound is dehydrated to the target tetrahydrofuran by means of TFA, PdCl2/Cu(NO3)2 or MsCl/pyridine.
| 【1】 Biftu, T.; Chabala, J.C.; Acton, J.; Kuo, C.-H.; Stevenson, R.; 2,5-DIARYLTETRAHYDROFURANS: PAF ANTAGONISTS. Drugs Fut 1989, 14, 4, 359. |
| 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) | 44362 | 1-(3,4,5-trimethoxyphenyl)-1-ethanone | 1136-86-3 | C11H14O4 | 详情 | 详情 |
| (II) | 44363 | 3-(dimethylamino)-1-(3,4,5-trimethoxyphenyl)-1-propanone | C14H21NO4 | 详情 | 详情 | |
| (III) | 27941 | 1-(3,4,5-trimethoxyphenyl)-2-propen-1-one | C12H14O4 | 详情 | 详情 | |
| (IV) | 44364 | 3-methoxy-5-(methylsulfonyl)-4-propoxybenzaldehyde | C12H16O5S | 详情 | 详情 | |
| (V) | 44365 | 3,4-diethyl-5-(2-hydroxyethyl)-1,3-thiazol-3-ium bromide | C9H16BrNOS | 详情 | 详情 | |
| (VI) | 44366 | 1-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-4-(3,4,5-trimethoxyphenyl)-1,4-butanedione | C24H30O9S | 详情 | 详情 | |
| (VII) | 44367 | 4-hydroxy-4-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-1-butanone | C24H32O9S | 详情 | 详情 | |
| (VIII) | 44368 | (1R,4R)-1-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-4-(3,4,5-trimethoxyphenyl)-1,4-butanediol | C24H34O9S | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(II)The selective monoreduction of the already known (see scheme 14265002a) 1-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-4-(3,4,5-trimethoxyphenyl)butane-1,4-dione (I) with LiAlH(O-t-Bu)3 in THF gives the hydroxybutanone (II) as a racemic mixture that is separated by esterification with (-)-(R)-mandelic acid, separation of diastereomers and hydrolysis with KOH in ethanol yielding (S)-(III) and (R)-(IV) as pure enantiomers. The reduction of both (S)-(III) and (R)-(IV) with NaBH4 in hot ethanol gives (S)-(V) and (R)-(VI) diols that are cyclized by means of TFA in chloroform to afford trans-(S,S)- and trans-(R,R)-target compounds. Both compounds are impurified with about 25% of the corresponding cis-isomer that is separated by chromatography.
| 【1】 Chabala, J.C.; Buglanesi, R.L.; Ponpipom, M.M.; Enantioselective cyclization of chiral butane-1, 4-diols to chiral tetrahydrofurans: Synthesis of chiral trans-2-(3-methoxy-5-methylsulfonyl-4-propoxyphenyl)-5-(3,4,5-trimethoxyphenyl)tetrahydrofuran (L-659,989), a potent PAF-receptor antagonist. Tetrahedron Lett 1988, 29, 48, 6211. |
| 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) | 44366 | 1-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-4-(3,4,5-trimethoxyphenyl)-1,4-butanedione | C24H30O9S | 详情 | 详情 | |
| (II) | 44367 | 4-hydroxy-4-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-1-butanone | C24H32O9S | 详情 | 详情 | |
| (III) | 44371 | (4S)-4-hydroxy-4-[3-methoxy-5-(methylsulfonyl)-4-propoxyphenyl]-1-(3,4,5-trimethoxyphenyl)-1-butanone | C24H32O9S | 详情 | 详情 | |
| (IV) | 44372 | 5-methoxy-1,1-bis(phenylsulfanyl)-3,4-dihydro-2(1H)-naphthalenone | C23H20O2S2 | 详情 | 详情 | |
| (V) | 44373 | tert-butyl 2-(bromomethyl)acrylate | C8H13BrO2 | 详情 | 详情 | |
| (VI) | 44374 | tert-butyl 2-[[8-methoxy-3-oxo-4,4-bis(phenylsulfanyl)-1,2,3,4-tetrahydro-2-naphthalenyl]methyl]acrylate | C31H32O4S2 | 详情 | 详情 |