6'-allyloxy-3-(benzo[b]furan-5-yl)-2'-hydroxypropiophenone 2'-O-β-D-glucopyranoside | 217634-73-6

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 6'-allyloxy-3-(benzo[b]furan-5-yl)-2'-hydroxypropiophenone 2'-O-β-D-glucopyranoside
• 英文别名: 6'-allyloxy-2-(benzofuran-5-yl)-2'-hydroxypropiophenone 2'-O-β-D-glucopyranoside；3-(1-benzofuran-5-yl)-1-[2-prop-2-enoxy-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]propan-1-one
• CAS: 217634-73-6
• 化学式: C₂₆H₂₈O₉
• 分子量: 484.503
• InChiKey: AMQCTMWXNRIGEH-XDXGNBCUSA-N

物化性质

• 沸点：
  725.3±60.0 °C(predicted)
• 密度：
  1.367±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  35
• 可旋转键数：
  10
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  139
• 氢给体数：
  4
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  6'-allyloxy-3-(benzo[b]furan-5-yl)-2'-hydroxypropiophenone 2'-O-β-D-glucopyranoside 在 2,4,6-三甲基吡啶 、 bis-triphenylphosphine-palladium(II) chloride 、 ammonium formate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 6.5h， 生成 [(2R,3S,4S,5R,6S)-6-[2-[3-(1-benzofuran-5-yl)propanoyl]-3-hydroxyphenoxy]-3,4,5-trihydroxyoxan-2-yl]methyl N-phenylcarbamate
  参考文献：
  名称：

  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.

  摘要：

  为了克服消化道中β-葡萄糖苷酶对4'-去氢氧基根皮苷衍生物（1、2、3）的水解作用，对其葡萄糖部分上的羟基进行了多种模式的修饰，随后评估了这些修饰化合物对大鼠尿糖排泄的影响。其中，三乙酰化（9）、2,3-二乙酰化（17）、6-O-甲氧羰基化（34）、4-O-甲氧羰基化（38）和2-O-乙酰化（41）衍生物通过口服给药（p.o.）显示出比母体化合物2更强的效果。化合物34、38和41对β-葡萄糖苷酶的稳定性高于化合物2。口服活性的增加与对β-葡萄糖苷酶稳定性的增强相关。

  DOI：

  10.1248/cpb.46.1545
• 作为产物：
  描述：

  3-溴丙烯 、 2'-(β-D-glucopyranosyloxy)-6'-hydroxy-3-(5-benzo[b]-furanyl)propiophenone 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 反应 5.0h， 以89%的产率得到6'-allyloxy-3-(benzo[b]furan-5-yl)-2'-hydroxypropiophenone 2'-O-β-D-glucopyranoside
  参考文献：
  名称：

  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.

  摘要：

  为了克服消化道中β-葡萄糖苷酶对4'-去氢氧基根皮苷衍生物（1、2、3）的水解作用，对其葡萄糖部分上的羟基进行了多种模式的修饰，随后评估了这些修饰化合物对大鼠尿糖排泄的影响。其中，三乙酰化（9）、2,3-二乙酰化（17）、6-O-甲氧羰基化（34）、4-O-甲氧羰基化（38）和2-O-乙酰化（41）衍生物通过口服给药（p.o.）显示出比母体化合物2更强的效果。化合物34、38和41对β-葡萄糖苷酶的稳定性高于化合物2。口服活性的增加与对β-葡萄糖苷酶稳定性的增强相关。

  DOI：

  10.1248/cpb.46.1545

文献信息

• Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring
  作者：Kenji Tsujihara、Mitsuya Hongu、Kunio Saito、Hiroyuki Kawanishi、Kayoko Kuriyama、Mamoru Matsumoto、Akira Oku、Kiichiro Ueta、Minoru Tsuda、Akira Saito

  DOI：10.1021/jm990175n

  日期：1999.12.1

  In our studies of Na+-glucose cotransporter (SGLT) inhibitors as antidiabetic agents, a series of novel 4'-dehydroxyphlorizin derivatives substituted on the B ring was prepared and their effects on urinary glucose excretion were evaluated in rats. Introduction of only a small alkyl group at the 4'-position increased the activity, and 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-beta-D-glucopyranoside (4) showed the most potent effect. To overcome hydrolysis of compound 4 by beta-glucosidase in the digestive tract, the OH groups on the glucose moiety of compound 4 were modified. Three prodrugs (5, 42, and 55) were more potent than the parent compound 4 by oral administration, and finally 3-(benzo[b]furan-5-yl)-2',6'-dihydroxy-4'-methylpropiophenone 2'-O-(6-O-methoxycarbonyl-beta-D-glucopyranoside) (5) was selected as a new promising candidate. Compound 5 was metabolized mainly by liver esterase to the active form (4), which was about 10 times more potent than 5 in inhibiting SGLT. In oral glucose tolerance test in db/db mice, compound 5 dose-dependently suppressed the elevation of glucose levels. Single administration of 5 reduced hyperglycemia concurrently with increase of glucose excretion into urine in diabetic KK-A(y) mice. Furthermore, compound 5 suppressed the elevation of blood glucose levels but did not lower it below the normal level even in fasted conditions in KK-A(y) mice. Additionally, long-term treatment with 5 dose-dependently reduced hyperglycemia and HbA1c in KK-A(y) mice. These pharmacological data strongly suggest that compound 5 has a therapeutic potential in the treatment of NIDDM.