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【结 构 式】 
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【分子编号】27261 【品名】(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 【CA登记号】 |
【 分 子 式 】C23H28O12 【 分 子 量 】496.46812 【元素组成】C 55.64% H 5.68% O 38.67% |
合成路线1
该中间体在本合成路线中的序号：(V)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 |
合成路线2
该中间体在本合成路线中的序号：(V)Orcinol (I) is acetylated with Ac2O in pyridine giving the diacetate (II), which is submitted to a Fries rearrangement with AlCl3 in hot chlorobenzene yielding acetophenone (III). Subsequent condensation of (III) with 2,3,4,6-tetra-O-acetyl-alpha-D-glucopyranosyl bromide (IV) by means of CdCO3 in refluxing toluene (or K2CO3 and tributylbenzylammonium chloride in dichloromethane) affords the glycosylated acetophenone (V), which is condensed with benzofuran-5-carbaldehyde (VI) by means of KOH in ethanol affording deacetylated chalcone (VII). Finally, this compound is hydrogenated with H2 over Pt/C in ethanol.
| 【1】 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. |
| 【2】 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 |
|---|---|---|---|---|---|---|
| (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 |