(1aR,1bS,6S,6aS)-6-butyltetrahydrooxireno[2′,3′:3,4]pyrrolo[1,2-c]oxazol-4(1aH)-one | 1268338-56-2

• 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: (1aR,1bS,6S,6aS)-6-butyltetrahydrooxireno[2′,3′:3,4]pyrrolo[1,2-c]oxazol-4(1aH)-one
• 英文别名: (1S,2R,4S,5S)-5-butyl-3,8-dioxa-6-azatricyclo[4.3.0.02,4]nonan-7-one
• CAS: 1268338-56-2
• 化学式: C₁₀H₁₅NO₃
• 分子量: 197.234
• InChiKey: BAQDZTLGONOUJY-XSPKLOCKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  42.1
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1aR,1bS,6S,6aS)-6-butyltetrahydrooxireno[2′,3′:3,4]pyrrolo[1,2-c]oxazol-4(1aH)-one 在 水 、 三氟乙酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醇 、 水 为溶剂， 反应 84.0h， 生成 1-n-butyl-L-aravinoiminofuranose
  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：

  (5R,7aR)-5-(hydroxymethyl)-5,7a-dihydro-1H-pyrrolo[1,2-c][1,3]oxazol-3-one 在 咪唑 、 Oxone 、 bis(1,5-cyclooctadiene)nickel (0) 、 乙二胺四乙酸 、 1,1,1-三氟丙酮 、 碘 、 碳酸氢钠 、 (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 、 水 、 乙腈 为溶剂， 反应 28.75h， 生成 (1aR,1bS,6S,6aS)-6-butyltetrahydrooxireno[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

文献信息

• The synthesis and biological evaluation of 1-C-alkyl-l-arabinoiminofuranoses, a novel class of α-glucosidase inhibitors
  作者：Yoshihiro Natori、Tatsushi Imahori、Keiichi Murakami、Yuichi Yoshimura、Shinpei Nakagawa、Atsushi Kato、Isao Adachi、Hiroki Takahata

  DOI：10.1016/j.bmcl.2010.11.112

  日期：2011.1

  The asymmetric synthesis of 1-C-alkyl-L-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC50 values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity (IC50 = 0.032 mu M) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs. (C) 2010 Elsevier Ltd. All rights reserved.
• [EN] AGENT FOR AMELIORATING POSTPRANDIAL HYPERGLYCEMIA, AND PYRROLIDINE IMINOSUGAR OR SALT THEREOF<br/>[FR] AGENT PERMETTANT D'AMÉLIORER L'HYPERGLYCÉMIE POST-PRANDIALE ET IMINOSUCRE DE PYRROLIDINE OU SEL DE CELUI-CI
  申请人：NAT UNIV CORP UNIV TOYAMA

  公开号：WO2011058975A1

  公开（公告）日：2011-05-19

  　下記一般式［１］で表されるピロリジン型イミノ糖またはその塩を含有する食後過血糖改善剤。［式中、Ｒ１は、アリール基、ヒドロキシ基、および、保護されたヒドロキシ基からなる群から選択される基で置換されていてもよいアルキル基を示し；Ｒ２は、水素原子、アルキル基またはイミノ保護基を示し；Ｒ３、Ｒ４およびＲ５はそれぞれ、同一または異なって、水素原子またはヒドロキシ保護基を示す。］
• 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.