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【结 构 式】 
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【药物名称】T-1095, RWJ-394718 【化学名称】3-(5-Benzofuranyl)-1-[2-hydroxy-6-[6-O-(methoxycarbonyl)- β-D-glucopyranosyloxy]-4-methylphenyl]-1- propanone 【CA登记号】 【 分 子 式 】C26H28O11 【 分 子 量 】516.50646 |
【开发单位】Tanabe 【药理作用】TREATMENT OF LIVER AND BILIARY TRACT DISORDERS |
合成路线1
Orcinol (I) was acetylated with Ac2O in pyridine to give diacetate (II), which was submitted to a Fries rearrangement in the presence of AlCl3 in chlorobenzene at 90 C to afford acetophenone (III). Subsequent condensation of (III) with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (IV) was effected either in the presence of CdCO3 in boiling toluene or K2CO3 and tributyl benzylammonium chloride in CH2Cl2 at r.t. The resulting (glucopyranosyloxy)acetophenone (V) was condensed with 5-formylbenzofuran (VI) in the presence of KOH to give chalcone (VII). Hydrogenation of (VII) over Pt/C then yielded the (benzofuranyl)propiophenone (VIII). After protection of the 6'-hydroxyl group of (VIII) as the allyl ether (X) with allyl bromide (IX) and K2CO3, the primary alcohol of (X) was acylated with ClCOOMe to furnish carbonate ester (XI). Finally, the O-allyl group of (XI) was cleaved with palladium catalyst and ammonium formate.
| 【1】 Doggrell, S.A.; Castañer, J.; T-1095. Drugs Fut 2001, 26, 8, 750. |
| 【2】 Tsujihara, K.; et al.; Na+-glucose contransporter (SGLT) inhibitors as antidiabetic agents. 4. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives substituted on the B ring. J Med Chem 1999, 42, 26, 5311. |
| 【3】 Hongu, M.; Matsumoto, M.; Oku, A.; Saito, K.; Tsujihara, K. (Tanabe Seiyaku Co., Ltd.); Propiophenone derivs. and process for preparing the same. EP 0850948; JP 1998237089; US 6048842 . |
| 中间体序号 | 中间体编号 | 品名 | CAS号 | 分子式 | 供应商 | 用于合成 |
|---|---|---|---|---|---|---|
| 16993 | methyl chlorocarbonate;Carbonochloridic acid methyl ester；[(chlorocarbonyl)oxy]methane；methyl chloroformate | 79-22-1 | C2H3ClO2 | 详情 | 详情 | |
| (I) | 27257 | 5-Methyl-1,3-benzenediol; Orcinol | 505-15-4 | C7H8O2 | 详情 | 详情 |
| (II) | 27258 | 3-(acetoxy)-5-methylphenyl acetate | C11H12O4 | 详情 | 详情 | |
| (III) | 27259 | 1-(2,6-dihydroxy-4-methylphenyl)-1-ethanone | C9H10O3 | 详情 | 详情 | |
| (IV) | 27260 | (2R,3R,4S,5S,6R)-4,5-bis(acetoxy)-6-[(acetoxy)methyl]-2-bromotetrahydro-2H-pyran-3-yl acetate | 572-09-8 | C14H19BrO9 | 详情 | 详情 |
| (V) | 27261 | (2R,3R,4S,5R,6S)-6-(2-acetyl-3-hydroxy-5-methylphenoxy)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-2H-pyran-3-yl acetate | C23H28O12 | 详情 | 详情 | |
| (VI) | 27262 | 1-benzofuran-5-carbaldehyde | C9H6O2 | 详情 | 详情 | |
| (VII) | 27263 | (E)-3-(1-benzofuran-5-yl)-1-(2-hydroxy-4-methyl-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-2-propen-1-one | C24H24O9 | 详情 | 详情 | |
| (VIII) | 27264 | 3-(1-benzofuran-5-yl)-1-(2-hydroxy-4-methyl-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-1-propanone | C24H26O9 | 详情 | 详情 | |
| (IX) | 11463 | 3-Bromo-1-propene; 3-Bromopropene；allyl bromide | 106-95-6 | C3H5Br | 详情 | 详情 |
| (X) | 27265 | 1-(2-(allyloxy)-4-methyl-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-3-(1-benzofuran-5-yl)-1-propanone | C27H30O9 | 详情 | 详情 | |
| (XI) | 27266 | ((2R,3S,4S,5R,6S)-6-[3-(allyloxy)-2-[3-(1-benzofuran-5-yl)propanoyl]-5-methylphenoxy]-3,4,5-trihydroxytetrahydro-2H-pyran-2-yl)methyl methyl carbonate | C29H32O11 | 详情 | 详情 |