(1S,8aR)-8-(1,3-dioxolan-2-yl)-1-hydroxy-1,5,6,8a-tetrahydro-2H-indolizin-3-one | 1127424-74-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (1S,8aR)-8-(1,3-dioxolan-2-yl)-1-hydroxy-1,5,6,8a-tetrahydro-2H-indolizin-3-one
• 英文别名: (1S,8aR)-8-(1,3-dioxolan-2-yl)-1-hydroxy-2,5,6,8a-tetrahydro-1H-indolizin-3-one
• CAS: 1127424-74-1
• 化学式: C₁₁H₁₅NO₄
• 分子量: 225.244
• InChiKey: BIJIFOXGVJCULO-WCBMZHEXSA-N

物化性质

• 熔点：
  143.5-144.0 °C(Solvent: Hexane; Ethyl acetate)
• 沸点：
  428.7±45.0 °C(predicted)
• 密度：
  1.38±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.5
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  59
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,8aR)-8-(1,3-dioxolan-2-yl)-1-hydroxy-1,5,6,8a-tetrahydro-2H-indolizin-3-one 在 4-二甲氨基吡啶 、 硫代氯甲酸苯酯 、 偶氮二异丁腈 、 三正丁基氢锡 作用下， 以 1,2-二氯乙烷 、 苯 为溶剂， 反应 0.5h， 生成 (8aS)-8-(1,3-dioxolan-2-yl)-1,5,6,8a-tetrahydro-2H-indolizin-3-one
  参考文献：
  名称：

  Synthesis and evaluation of opioid receptor-binding affinity of elaeocarpenine and its analogs

  摘要：

  Both enantiomers of elaeocarpenine (1) and its analogs, 21, 22, 25, and 27, were synthesized from bicyclic aldehydes 8-10 via a flexible route previously established for total synthesis of grandisines, and their binding affinities for mu-, kappa- and delta-opioid receptor subtypes were evaluated. We found that (9R)-1 exhibited higher affinity than (9S)-1 for all the subtypes, but the enantiomers showed little subtype selectivity. Analogs 21 having a pyrrolizidine skeleton and 27 having a stemona-type skeleton in place of the indolizidine unit of (9S)-1 showed mu-selective and mu-, kappa-selective binding, respectively. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.01.062
• 作为产物：
  描述：

  (1S,8aR)-8-[1,3-dioxolan-2-yl]-3-oxo-1,2,3,5,6,8a-hexahydroindolizin-1-yl acetate 在 乙醇 、 sodium ethanolate 作用下， 以70%的产率得到(1S,8aR)-8-(1,3-dioxolan-2-yl)-1-hydroxy-1,5,6,8a-tetrahydro-2H-indolizin-3-one
  参考文献：
  名称：

  大黄素D的全合成

  摘要：

  通过布朗斯台德酸介导的森田-贝利斯-希尔曼（MBH）闭环反应和立体选择性醛醇缩合反应（S）-5-甲基环己烯酮（9）作为关键步骤，实现了金刚烷D（5）的总合成。MBH方法也可用于吡咯烷和草醚生物碱的氮杂稠合双环系统的构建。

  DOI：

  10.1021/ol900032h

文献信息

• A Flexible Approach to Grandisine Alkaloids: Total Synthesis of Grandisines B, D, and F
  作者：Haruaki Kurasaki、Iwao Okamoto、Nobuyoshi Morita、Osamu Tamura

  DOI：10.1002/chem.200901843

  日期：2009.11.23

  first total synthesis of grandisine alkaloids, grandisines B, D, and F, which show affinity for the human δ‐opioid receptor. The key steps in this synthesis are construction of the isoquinuclidinone moiety of 2 by intramolecular imine formation and the tetracyclic ring system of 4 by stereoselective ring closure of the enolate of amine 8 generated by 1,4‐addition of ammonia to 9. Synthesis of key intermediate

  本文详细介绍了金丝雀碱生物碱，金丝雀碱B，D和F的第一种全合成方法，它们对人的δ阿片受体具有亲和力。该合成的关键步骤是通过分子内亚胺的形成来构建2的异奎宁环酮部分，并通过将1，4加成氨到9生成的胺8的烯醇的立体选择性闭环来构建4的四环体系。关键中间体9的合成具有通过N-酰基亚胺离子高度立体选择性的布朗斯台德酸介导的森田-贝利斯-希尔曼（MBH）反应。
• Total Synthesis of Grandisine D
  作者：Haruaki Kurasaki、Iwao Okamoto、Nobuyoshi Morita、Osamu Tamura

  DOI：10.1021/ol900032h

  日期：2009.3.5

  Total synthesis of grandisine D (5) was achieved by a Brønsted acid mediated Morita−Baylis−Hillman (MBH) ring-closure reaction and stereoselective aldol condensation with (S)-5-methylcyclohexenone (9) as key steps. The MBH approach was also applicable for the construction of the aza-fused bicyclic systems of pyrrolizidine and stemona alkaloids.

  通过布朗斯台德酸介导的森田-贝利斯-希尔曼（MBH）闭环反应和立体选择性醛醇缩合反应（S）-5-甲基环己烯酮（9）作为关键步骤，实现了金刚烷D（5）的总合成。MBH方法也可用于吡咯烷和草醚生物碱的氮杂稠合双环系统的构建。
• Synthesis and evaluation of opioid receptor-binding affinity of elaeocarpenine and its analogs
  作者：Haruaki Kurasaki、Iwao Okamoto、Nobuyoshi Morita、Osamu Tamura

  DOI：10.1016/j.bmcl.2010.01.062

  日期：2010.3

  Both enantiomers of elaeocarpenine (1) and its analogs, 21, 22, 25, and 27, were synthesized from bicyclic aldehydes 8-10 via a flexible route previously established for total synthesis of grandisines, and their binding affinities for mu-, kappa- and delta-opioid receptor subtypes were evaluated. We found that (9R)-1 exhibited higher affinity than (9S)-1 for all the subtypes, but the enantiomers showed little subtype selectivity. Analogs 21 having a pyrrolizidine skeleton and 27 having a stemona-type skeleton in place of the indolizidine unit of (9S)-1 showed mu-selective and mu-, kappa-selective binding, respectively. (C) 2010 Elsevier Ltd. All rights reserved.