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【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%

与该中间体有关的原料药合成路线共 2 条

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
Extended Information