3-(benzo[b]furan-5-yl)-6'-tert-butyldimethylsilyloxy-2'-hydroxy-4'-methylpropiophenone 2'-O-(2-O-acetyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-β-D-glucopyranoside) | 209746-77-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-(benzo[b]furan-5-yl)-6'-tert-butyldimethylsilyloxy-2'-hydroxy-4'-methylpropiophenone 2'-O-(2-O-acetyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-β-D-glucopyranoside)
• 英文别名: 3-(5-benzo[b]furanyl)-2'-(2-O-acetyl-3-O-t-butyldimethylsilyl-4,6-O-benzylidene-β-D-glucopyranosyloxy)-6'-t-butyldimethylsilyloxy-4'-methylpropiophenone；[(4aR,6S,7R,8S,8aR)-6-[2-[3-(1-benzofuran-5-yl)propanoyl]-3-[tert-butyl(dimethyl)silyl]oxy-5-methylphenoxy]-8-[tert-butyl(dimethyl)silyl]oxy-2-phenyl-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-7-yl] acetate
• CAS: 209746-77-0
• 化学式: C₄₅H₆₀O₁₀Si₂
• 分子量: 817.136
• InChiKey: ZBJQGWBYPFINDE-RCIQQWFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  10.48
• 重原子数：
  57
• 可旋转键数：
  15
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.51
• 拓扑面积：
  112
• 氢给体数：
  0
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  3-(benzo[b]furan-5-yl)-6'-tert-butyldimethylsilyloxy-2'-hydroxy-4'-methylpropiophenone 2'-O-(2-O-acetyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-β-D-glucopyranoside) 在 四丁基氟化铵 、 溶剂黄146 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 生成 3-(5-benzo[b]furanyl)-2'-(2-O-acetyl-3-O-t-butyldimethylsilyl-4,6-O-benzylidene-β-D-glucopyranosyloxy)-6'-hydroxy-4'-methylpropiophenone
  参考文献：
  名称：

  Propiophenone derivatives and process for preparing the same

  摘要：

  一种具有以下结构的丙酮苯甲酮衍生物（I）：其中OX是一个氢氧基团，可以选择性地受保护，Y是一个较低的烷基基团，Z是一个β-D-葡萄糖吡喃基团，其中一个或多个氢氧基团可以选择性地受保护，或其药用盐。这些化合物具有出色的降糖活性，因此它们在糖尿病的预防或治疗中非常有用。

  公开号：

  US06048842A1
• 作为产物：
  描述：

  (E)-3-(1-benzofuran-5-yl)-1-[2-hydroxy-4-methyl-6-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]prop-2-en-1-one 在 platinum on activated charcoal 吡啶 、 咪唑 、 4-二甲氨基吡啶 、 对甲苯磺酸 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 36.5h， 生成 3-(benzo[b]furan-5-yl)-6'-tert-butyldimethylsilyloxy-2'-hydroxy-4'-methylpropiophenone 2'-O-(2-O-acetyl-4,6-O-benzylidene-3-O-tert-butyldimethylsilyl-β-D-glucopyranoside)
  参考文献：
  名称：

  Na⁺-Glucose Cotransporter (SGLT) Inhibitors as Antidiabetic Agents. 4. Synthesis and Pharmacological Properties of 4‘-Dehydroxyphlorizin Derivatives Substituted on the B Ring

  摘要：

  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.

  DOI：

  10.1021/jm990175n