|
【结 构 式】 
|
【分子编号】27513 【品名】(E)-3-(1-benzofuran-5-yl)-1-(2-hydroxy-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-2-propen-1-one 【CA登记号】 |
【 分 子 式 】C23H22O9 【 分 子 量 】442.42228 【元素组成】C 62.44% H 5.01% O 32.55% |
合成路线1
该中间体在本合成路线中的序号：(V)Reaction of 2,6-dihydroxyacetophenone (I) with acetylated bromoglucose (II) in the presence of CdCO3 in refluxing toluene, with water removal using a Dean Stark apparatus, afforded glycoside (III). Potassium hydroxide-promoted condensation of acetophenone (III) with benzofuran-5-carboxyaldehyde (IV), with concomitant hydrolysis of acetate esters, gave enone (V), which was hydrogenated over Pt/C in the presence of DMAP to provide dihydrochalcone derivative (VI). Treatment of (VI) with benzaldehyde dimethylacetal (VII) and p-TsOH gave benzylidene acetal (VIII). This compound was acetylated with Ac2O and pyridine to yield (IX).
| 【1】 Tsujihara, K.; et al.; Na+-glucose cotransporter inhibitors as antidiabetics. I. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives based on a new concept. Chem Pharm Bull 1996, 44, 6, 1174. |
| 【2】 Hongu, M.; et al.; Na+-Glucose cotransporter inhibitors as antidiabetic agents. II. Synthesis and structure-activity relationships of 4'-dehydroxyphlorizin derivatives. Chem Pharm Bull 1998, 46, 1, 22. |
| 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) | 27511 | 1-(2,6-dihydroxyphenyl)-1-ethanone | 699-83-2 | C8H8O3 | 详情 | 详情 |
| (II) | 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 |
| (III) | 27512 | (2R,3R,4S,5R,6S)-6-(2-acetyl-3-hydroxyphenoxy)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-2H-pyran-3-yl acetate | C22H26O12 | 详情 | 详情 | |
| (IV) | 27262 | 1-benzofuran-5-carbaldehyde | C9H6O2 | 详情 | 详情 | |
| (V) | 27513 | (E)-3-(1-benzofuran-5-yl)-1-(2-hydroxy-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-2-propen-1-one | C23H22O9 | 详情 | 详情 | |
| (VI) | 27514 | 3-(1-benzofuran-5-yl)-1-(2-hydroxy-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-1-propanone | C23H24O9 | 详情 | 详情 | |
| (VII) | 27515 | Methoxy(phenyl)methyl methyl ether; Dimethylacetal benzaldehyde; Benzaldehyde dimethylacetal | 1125-88-8 | C9H12O2 | 详情 | 详情 |
| (VIII) | 27516 | 1-(2-[[(4aR,6S,7R,8R,8aS)-7,8-dihydroxy-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-6-yl]oxy]-6-hydroxyphenyl)-3-(1-benzofuran-5-yl)-1-propanone | C30H28O9 | 详情 | 详情 | |
| (IX) | 27517 | (4aR,6S,7R,8S,8aR)-7-(acetoxy)-6-[3-(acetoxy)-2-[3-(1-benzofuran-5-yl)propanoyl]phenoxy]-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl acetate | C36H34O12 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(V)Reaction of 2,6-dihydroxyacetophenone (I) with acetylated bromoglucose (II) in the presence of CdCO3 in refluxing toluene, with water removal using a Dean Stark apparatus, afforded glycoside (III). Potassium hydroxide-promoted condensation of acetophenone (III) with benzofuran-5-carboxyaldehyde (IV), with concomitant hydrolysis of acetate esters, gave enone (V), which was hydrogenated over Pt/C in the presence of DMAP to provide dihydrochalcone derivative (VI). Treatment of (VI) with 4-nitrophenyl chloroformate (VII) and 2,4,6-collidine gave the intermediate 6-O-(4-nitrophenylcarbonyl) compound, which is cyclized to the cyclic carbonate (VIII) by heating at 50 C. The ring opening reaction of (VIII) with TsOH and methanol afforded the target 4-O-(methoxycarbonyl) compound along with some 6-O-methoxycarbonyl isomer, which is separated by column chromatography.
| 【1】 Hongu, M.; et al.; Na+-Glucose cotransporter inhibitors as antidiabetic agents. II. Synthesis and structure-activity relationships of 4'-dehydroxyphlorizin derivatives. Chem Pharm Bull 1998, 46, 1, 22. |
| 【2】 Tsujihara, K.; et al.; Na+-glucose cotransporter inhibitors as antidiabetics. I. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives based on a new concept. Chem Pharm Bull 1996, 44, 6, 1174. |
| 【3】 Hongu, M.; Funami, N.; Takahashi, Y.; Saito, K.; Arakawa, K.; Matsumoto, M.; Yamakita, H.; Tsujihara, K.; Na+-glucose cotransporter inhibitors as antidiabetic agents. III. Synthesis and pharmacological properties of 4'-dehydroxyphlorizin derivatives modified at the OH groups of the glucose moiety. Chem Pharm Bull 1998, 46, 10, 1545. |
| 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) | 27511 | 1-(2,6-dihydroxyphenyl)-1-ethanone | 699-83-2 | C8H8O3 | 详情 | 详情 |
| (II) | 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 |
| (III) | 27512 | (2R,3R,4S,5R,6S)-6-(2-acetyl-3-hydroxyphenoxy)-4,5-bis(acetoxy)-2-[(acetoxy)methyl]tetrahydro-2H-pyran-3-yl acetate | C22H26O12 | 详情 | 详情 | |
| (IV) | 27262 | 1-benzofuran-5-carbaldehyde | C9H6O2 | 详情 | 详情 | |
| (V) | 27513 | (E)-3-(1-benzofuran-5-yl)-1-(2-hydroxy-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-2-propen-1-one | C23H22O9 | 详情 | 详情 | |
| (VI) | 27514 | 3-(1-benzofuran-5-yl)-1-(2-hydroxy-6-[[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yl]oxy]phenyl)-1-propanone | C23H24O9 | 详情 | 详情 | |
| (VII) | 16605 | 4-Nitrophenyl chloroformate; 1-[(Chlorocarbonyl)oxy]-4-nitrobenzene | 7693-46-1 | C7H4ClNO4 | 详情 | 详情 |
| (VIII) | 27520 | (4aR,6S,7R,8R,8aS)-6-[2-[3-(1-benzofuran-5-yl)propanoyl]-3-hydroxyphenoxy]-7,8-dihydroxyhexahydropyrano[3,2-d][1,3]dioxin-2-one | C24H22O10 | 详情 | 详情 |