8-benzoyl-8-azabicyclo[3.2.1]octan-3-one

• 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: 8-benzoyl-8-azabicyclo[3.2.1]octan-3-one
• 英文别名: (1R,5S)-8-benzoyl-8-azabicyclo-[3.2.1]octan-3-one；(1S,5R)-8-benzoyl-8-azabicyclo[3.2.1]octan-3-one
• 化学式: C₁₄H₁₅NO₂
• 分子量: 229.279
• InChiKey: OATQBSPRXZUSJZ-TXEJJXNPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  37.4
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-benzoyl-8-azabicyclo[3.2.1]octan-3-one 、 三甲基碘化亚砜 在 sodium hydride 作用下， 以 二甲基亚砜 、 mineral oil 为溶剂， 反应 4.25h， 以88%的产率得到8-benzoylspiro[8-azabicyclo[3.2.1]octane-3,2'-oxirane]
  参考文献：
  名称：

  Novel Pyridylmethylamines as Highly Selective 5-HT_1A Superagonists

  摘要：

  To further improve the maximal serotonergic efficacy and better understand the configurational requirements for 5-HT1A binding and activation, we generated and biologically investigated structural variants of the lead structure befiradol. For a bioisosteric replacement of the 3-chloro-4-fluoro moiety, a focused library of 63 compounds by solution phase parallel synthesis was developed. Target binding of our compound collection was investigated, and their affinities for 5-HT2, alpha(1), and alpha(2)-adrenergic as well as D-1-D-4 at dopamine receptors were compared. For particularly interesting test compounds, intrinsic activities at 5-HT1A were examined in vitro employing a GTP gamma S assay. The investigation guided as to highly selective 5HT(1A) superagonists. The benzothiophene-3-carboxamide 8bt revealed almost exclusive 5HT(1A) recognition with a K-i value of 2.7 nM and a maximal efficacy of 124%. To get insights into the bioactive conformation of our compound collection, we synthesized conformationally constrained bicyclic scaffolds when SAR data indicated a chair-type geometry and an equatorially dispositioned aminomethyl substituent for the 4,4-disubstituted piperidine moiety.

  DOI：

  10.1021/jm100835q
• 作为产物：
  描述：

  tropinone 在 1-氯乙基氯甲酸酯 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 4.67h， 生成 8-benzoyl-8-azabicyclo[3.2.1]octan-3-one
  参考文献：
  名称：

  Synthesis and Antibacterial Activity of Novel [3-(4-substitutedphenylamino)-8-azabicyclo [3.2.1] oct-8yl]-phenyl-methanone Derivatives

  摘要：

  本文描述了新型[3-(4-取代苯基氨基)-8-氮杂双环[3.2.1]辛-8-基]-苯基-甲酮衍生物的合成、光谱和生物学研究。所有合成的化合物均通过元素分析FTIR、$^1H$-NMR、$^{13}C$ NMR和质谱数据进行了表征。所有合成的化合物均表现出体外抗菌活性。

  DOI：

  10.5012/jkcs.2011.55.6.969

文献信息

• Amide Bond Formation through Iron-Catalyzed Oxidative Amidation of Tertiary Amines with Anhydrides
  作者：Yuanming Li、Lina Ma、Fan Jia、Zhiping Li

  DOI：10.1021/jo400804p

  日期：2013.6.7

  for synthesis of tertiary amides from readily available tertiary amines and anhydrides in the presence of FeCl2 as catalyst and tert-butyl hydroperoxide in water (T-Hydro) as oxidant. Mechanistic studies indicated that the in situ-generated α-amino peroxide of tertiary amine and iminium ion act as key intermediates in this oxidative transformation.

  已经开发了用于酰胺键合成的通用且有效的方法。该方法允许在FeCl 2作为催化剂和叔丁基过氧化氢水溶液（T-Hydro）存在下由易得的叔胺和酸酐合成叔酰胺。机理研究表明，原位生成的叔胺和亚胺离子的α-氨基过氧化物是该氧化转化过程中的关键中间体。
• Selective Synthesis of N-Acylnortropane Derivatives in Palladium-Catalysed Aminocarbonylation
  作者：László Kollár、Ádám Erdélyi、Haroon Rasheed、Attila Takács

  DOI：10.3390/molecules26061813

  日期：——

  catalysts. In the presence of several iodo(hetero)arenes, the application of the bidentate Xantphos was necessary to produce the target compounds selectively. The new carboxamides of varied structure, formed in palladium-catalyzed aminocarbonylation reactions, were isolated and fully characterized. In this way, a novel synthetic method has been developed for the producing of N-acylnortropane derivatives of

  各种烯基碘和（杂）芳基碘化物的氨基羰基化反应均使用具有生物重要性的基于环烷的胺进行，例如8-氮杂双环[3.2.1]辛丹-3-酮（降冰片碱）和3α-羟基-8-氮杂双环[ 3.2.1]辛烷（降冰片）为N-亲核试剂。使用iodOAlkenes，两个亲核体被选择性地转化为相应的酰胺在Pd的存在下（OAC）2 / 2pph的3催化剂。在几种碘（杂）芳烃的存在下，必须应用双齿黄药来选择性地生产目标化合物。分离并充分表征了在钯催化的氨基羰基化反应中形成的各种结构的新酰胺。通过这种方式，已经开发出一种新颖的合成方法来生产具有重要生物意义的N-酰基邻苯烷。
• Organocatalytic Enantioselective Synthesis of Seven‐Membered Ring with Inherent Chirality
  作者：Jia‐Hao Li、Xiao‐Kai Li、Jia Feng、Wang Yao、Huan Zhang、Chuan‐Jun Lu、Ren‐Rong Liu

  DOI：10.1002/anie.202319289

  日期：2024.2.19

  Developing efficient protocols to construct inherent chirality is highly desirable owing to its tremendous application in chiral recognition and enantioselective synthesis. Herein, we report the first enantioselective synthesis of 7-membered inherently chiral derivatives via chiral phosphoric acid-catalyzed condensation. This chemistry highlights the broad substrate scope and excellent stereocontrol

  由于其在手性识别和对映选择性合成中的巨大应用，开发有效的方案来构建固有手性是非常可取的。在此，我们报告了通过手性磷酸催化缩合首次对映选择性合成7元固有手性衍生物。这种化学特性突出了广泛的底物范围和出色的立体控制（高达 99% ee）。