-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】2'-(2-O-Acetyl-beta-D-glucopyranosyloxy)-3-(benzofuran-5-yl)-6'-hydroxypropiophenone

【CA登记号】190777-97-0

【分子式】C₂₅H₂₆O₁₀

【分子量】486.47997

【开发单位】Tanabe Seiyaku (Originator)

【药理作用】Antidiabetic Drugs, ENDOCRINE DRUGS

合成路线1 合成路线2

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 benzaldehyde dimethylacetal (VII) and p-TsOH gave benzylidene acetal (VIII). This compound was acetylated with Ac2O and pyridine to yield (IX).

参考文献中间体

【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

Then, the phenolic acetate group of the resulting triacetate (IX) was selectively removed by treatment with NaHCO3 in MeOH affording (X). Subsequent hydrolysis of the benzylidene acetal of (X) with aqueous AcOH at 70 C gave diacetyl compound (XI). Finally, selective deacetylation in MeOH in the presence of p-TsOH at 40 C provided the desired 2-O-acetyl derivative accompanied by some 3-O-acetyl isomer, which was separated by column chromatography.

参考文献中间体

【1】 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	分子式	供应商	用于合成
(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
(X)	27518	(4aR,6S,7R,8S,8aR)-7-(acetoxy)-6-[2-[3-(1-benzofuran-5-yl)propanoyl]-3-hydroxyphenoxy]-2-phenylhexahydropyrano[3,2-d][1,3]dioxin-8-yl acetate	C₃₄H₃₂O₁₁	详情	详情
(XI)	27519	(2S,3R,4S,5R,6R)-3-(acetoxy)-2-[2-[3-(1-benzofuran-5-yl)propanoyl]-3-hydroxyphenoxy]-5-hydroxy-6-(hydroxymethyl)tetrahydro-2H-pyran-4-yl acetate	C₂₇H₂₈O₁₁	详情	详情

Extended Information