(5S,7aR)-5-(4-phenylbutyl)-1,7a-dihydropyrrolo[1,2-c]oxazol-3(5H)-one | 1414857-84-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: (5S,7aR)-5-(4-phenylbutyl)-1,7a-dihydropyrrolo[1,2-c]oxazol-3(5H)-one
• 英文别名: (5S,7aR)-5-(4-phenylbutyl)-5,7a-dihydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one
• CAS: 1414857-84-3
• 化学式: C₁₆H₁₉NO₂
• 分子量: 257.332
• InChiKey: XGKQZSZYRYOVGR-LSDHHAIUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (5S,7aR)-5-(4-phenylbutyl)-1,7a-dihydropyrrolo[1,2-c]oxazol-3(5H)-one 在 Oxone 、 乙二胺四乙酸 、 1,1,1-三氟丙酮 、 碳酸氢钠 作用下， 以 水 、 乙腈 为溶剂， 反应 2.75h， 生成 (1aR,1bS,6S,6aS)-6-(4-phenylbutyl)tetrahydrooxireno[2',3':3,4]pyrrolo[1,2-c]oxazol-4(1aH)-one
  参考文献：
  名称：

  α-1-C-Butyl-1,4-dideoxy-1,4-imino-l-arabinitol as a Second-Generation Iminosugar-Based Oral α-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia

  摘要：

  We report on the synthesis and the biological evaluation of a series of alpha-1-C-alkylated 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. alpha-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 mu M, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of alpha-1-C-butyl-LAB and miglitol are clearly different. Furthermore, a-l-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. alpha-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.

  DOI：

  10.1021/jm301304e
• 作为产物：
  描述：

  (R)-3-((R)-1-hydroxybut-3-en-2-yl)-4-vinyloxazolidin-2-one 在 咪唑 、 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 bis(1,5-cyclooctadiene)nickel (0) 、 碘 、 (S,S)-2,6-双(4-异丙基-2-恶唑啉-2-基)吡啶 、 三苯基膦 作用下， 以 二氯甲烷 、 N,N-二甲基乙酰胺 为溶剂， 反应 27.0h， 生成 (5S,7aR)-5-(4-phenylbutyl)-1,7a-dihydropyrrolo[1,2-c]oxazol-3(5H)-one
  参考文献：
  名称：

  α-1-C-Butyl-1,4-dideoxy-1,4-imino-l-arabinitol as a Second-Generation Iminosugar-Based Oral α-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia

  摘要：

  We report on the synthesis and the biological evaluation of a series of alpha-1-C-alkylated 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. alpha-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 mu M, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of alpha-1-C-butyl-LAB and miglitol are clearly different. Furthermore, a-l-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. alpha-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.

  DOI：

  10.1021/jm301304e

文献信息

• α-1-<i>C</i>-Butyl-1,4-dideoxy-1,4-imino-<scp>l</scp>-arabinitol as a Second-Generation Iminosugar-Based Oral α-Glucosidase Inhibitor for Improving Postprandial Hyperglycemia
  作者：Atsushi Kato、Erina Hayashi、Saori Miyauchi、Isao Adachi、Tatsushi Imahori、Yoshihiro Natori、Yuichi Yoshimura、Robert J. Nash、Hideyuki Shimaoka、Izumi Nakagome、Jun Koseki、Shuichi Hirono、Hiroki Takahata

  DOI：10.1021/jm301304e

  日期：2012.12.13

  We report on the synthesis and the biological evaluation of a series of alpha-1-C-alkylated 1,4-dideoxy-1,4-imino-L-arabinitol (LAB) derivatives. The asymmetric synthesis of the derivatives was achieved by asymmetric allylic alkylation, ring-closing metathesis, and Negishi cross-coupling as key reactions. alpha-1-C-Butyl-LAB is a potent inhibitor of intestinal maltase, isomaltase, and sucrase, with IC50 values of 0.13, 4.7, and 0.032 mu M, respectively. Matrix-assisted laser desorption ionization time-of-flight mass spectrometric analysis revealed that this compound differs from miglitol in that it does not influence oligosaccharide processing and the maturation of glycoproteins. A molecular docking study of maltase-glucoamylase suggested that the interaction modes and the orientations of alpha-1-C-butyl-LAB and miglitol are clearly different. Furthermore, a-l-C-butyl-LAB strongly suppressed postprandial hyperglycemia at an early phase, similar to miglitol in vivo. It is noteworthy that the effective dose was about 10-fold lower than that for miglitol. alpha-1-C-Butyl-LAB therefore represents a new class of promising compounds that can improve postprandial hyperglycemia.