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【结 构 式】 
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【药物名称】 【化学名称】3-(Benzofuran-5-yl)-2'-hydroxy-6'-[4-O-(methoxycarbonyl)-beta-D-glucopyranosyloxy]propiophenone 【CA登记号】190777-98-1 【 分 子 式 】C25H26O11 【 分 子 量 】502.47937 |
【开发单位】Tanabe Seiyaku (Originator) 【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS |
合成路线1
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 |