methyl (1R,3r,5S)-3-hydroxy-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate | 1148006-39-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 哌啶类
• 英文名称: methyl (1R,3r,5S)-3-hydroxy-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate
• CAS: 1148006-39-6
• 化学式: C₉H₁₃NO₃
• 分子量: 183.207
• InChiKey: INXLNJIRZZQHIN-RNLVFQAGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.52
• 重原子数：
  13.0
• 可旋转键数：
  0.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  49.77
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  methyl (1R,3r,5S)-3-hydroxy-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate 在 碘代三甲硅烷 、 potassium tert-butylate 、 三乙胺 作用下， 生成 isopropyl (1R,3r,5S)-3-((5-methyl-6-((2-methylpyridin-3-yl)oxy)pyrimidin-4-yl)oxy)-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate
  参考文献：
  名称：

  Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

  摘要：

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.035
• 作为产物：
  描述：

  methyl 3-oxo-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate 在 L-Selectride 、 三苯基膦 、 sodium hydroxide 、 偶氮二甲酸二乙酯 作用下， 以 水 为溶剂， 生成 methyl (1R,3r,5S)-3-hydroxy-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate
  参考文献：
  名称：

  Discovery of a nortropanol derivative as a potent and orally active GPR119 agonist for type 2 diabetes

  摘要：

  The lead optimization studies of a series of GPR119 agonists incorporating a nortropanol scaffold are described. Extensive structure-activity relationship (SAR) studies of the lead compound 20f led to the identification of compound 36j as a potent, single digit nanomolar GPR119 agonist with high agonist activity. Compound 36j was orally active in lowering blood glucose levels in a mouse oral glucose tolerance test and increased plasma insulin levels in a rat hyperglycemic model. It showed good to excellent pharmacokinetic properties in rats and monkeys and no untoward activities in counter-screen assays. Compound 36j demonstrated an attractive in vitro and in vivo profile for further development. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.04.035

文献信息

• Enantioselective desymmetrisation of an epoxytropinone for peduncularine synthesis
  作者：Ruth E. Shelton、Serdar Sezer、David M. Hodgson

  DOI：10.1016/j.tet.2020.131701

  日期：2020.12

  A key 7-allyl-8-hydroxy-6-azabicyclo[3.2.1]octan-3-one intermediate in a synthesis of the alkaloid peduncularine is obtained enantioenriched, by desymmetrisation of an achiral 6,7-epoxy-8-azabicyclo[3.2.1]octan-3-one (epoxytropinone). Chiral lithium amide-assisted enantioselective silyl enol ether formation then TMSOTf/allyltrimethylsilane/2,6-lutidine-induced rearrangement−allylation proceeded in

  通过非对称的非手性6,7-环氧-8-氮杂双环[[]]对称化获得生物碱peduncularine合成中的关键7-烯丙基-8-羟基-6-氮杂双环[3.2.1] octan-3-one中间体。 3.2.1] octan-3-one（环氧丁酮）。手性锂酰胺辅助的对映选择性甲硅烷基烯醇醚的形成，然后TMSOTf /烯丙基三甲基硅烷/ 2,6-二甲基吡啶诱导的重排-烯丙基化反应的进行时间高达80:20 er，但总收率不高。取代2,6-二甲基吡啶的手性胺或（硫代）脲直接从环氧肌酮中释放了76:24 er。使用BINOL衍生的双（磺酰基）酰亚胺催化剂和烯丙基三甲基硅烷进行的直接，简化（无碱）工艺证明是最有前途的（80％，83：17 er）。