3-Oxo-8-aza-bicyclo[3.2.1]oct-6-ene-8-carboxylic acid benzyl ester | 446873-84-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 3-Oxo-8-aza-bicyclo[3.2.1]oct-6-ene-8-carboxylic acid benzyl ester
• 英文别名: Benzyl 3-oxo-8-azabicyclo[3.2.1]oct-6-ene-8-carboxylate
• CAS: 446873-84-3
• 化学式: C₁₅H₁₅NO₃
• 分子量: 257.289
• InChiKey: HLPITGIQEMVIRG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-Oxo-8-aza-bicyclo[3.2.1]oct-6-ene-8-carboxylic acid benzyl ester 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 48.0h， 以82%的产率得到benzyl 7-oxo-3-oxa-9-azatricyclo[3.3.1.0(2,4)]nonane-9-carboxylate
  参考文献：
  名称：

  从生物碱生物碱：（±）-7a-的总合成外延-hyacinthacine阿1从ž通过拜尔-维利格氧化-保护tropenone

  摘要：

  已经研究了几种托烷衍生物的Baeyer-Villiger氧化反应。曲波酮15a – c仅进行环氧化成21a – c，而相应的6-氧代托环烷衍生物28则产生了所需的内酯29。对于O-异亚丙基保护的二醇32a，b，也可能进行Baeyer-Villiger氧化。将得到的内酯33A，b中的总合成方法采用（±）-7a-外延-hyacinthacine阿1（图7A- EPI - 7）通过将分子内亲核烷基锂加到氨基甲酸酯上作为关键的内酰胺化步骤。由曲戊酮15b分十步制备目标化合物，总产率为14％。吡咯烷（±）-36的酶解提供了对7的两个对映异构体的正式总合成。

  DOI：

  10.1016/j.tet.2009.05.071
• 作为产物：
  描述：

  benzyl 1H-pyrrole-1-carboxylate 在 diethylzinc 、 氯化铵 作用下， 以 甲醇 、 甲苯 为溶剂， 生成 3-Oxo-8-aza-bicyclo[3.2.1]oct-6-ene-8-carboxylic acid benzyl ester
  参考文献：
  名称：

  Synthesis and biological evaluation of both enantiomers of [18F]flubatine, promising radiotracers with fast kinetics for the imaging of α4β2-nicotinic acetylcholine receptors

  摘要：

  Both enantiomers of the epibatidine analogue flubatine display high affinity towards the alpha 4 beta 2 nicotinic acetylcholine receptor (nAChR) in vitro, accompanied by negligible interactions with diverse off-target proteins. Extended single dose toxicity studies in rodent indicated a NOEL (No Observed Effect Level) of 6.2 mu g/kg for (-)-flubatine and 1.55 mu g/kg for (+)-flubatine. We developed syntheses for both flubatine enantiomers and their corresponding precursors for radiolabeling. The newly synthesized trimethylammonium precursors allowed for highly efficient F-18-radiolabelling in radiochemical yields >60% and specific activities >750 GBq/mu mol, thus making the radioligands practical for clinical investigation. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.12.011

文献信息

• Enantioselective Desymmetrization of Tropinone Derivatives by Hydroboration
  作者：Sabine Laschat、Nicolai Cramer、Angelika Baro、Wolfgang Frey

  DOI：10.1055/s-2003-42080

  日期：——

  N-Protected tropenone derivatives 3, prepared from the respective pyrroles 5 and tetrabromoacetone (6), were used as starting materials for desymmetrization by hydroboration of the C-C double bond. Hydroboration of 3a with (-)-(Ipc)2BH followed by oxidation, however, gave the desired 6-hydroxylated product 4a only in low yield due to byproduct formation. After acetalization of the carbonyl group in 3, the corresponding acetals 8 were desymmetrized with (Ipc)2BH and oxidative workup to chiral alcohols 11 in good yields with excellent enantiomeric excesses in most cases.

  N-保护的热烯酮衍生物3，由相应的吡咯5和四溴乙酮（6）制备而成，被用作通过氢硼化对C-C双键进行不对称化的起始材料。然而，用(-)-(Ipc)2BH对3a进行氢硼化后，再进行氧化，得到所需的6-羟基化产物4a的产量仅很低，原因是副产物的形成。在对3中的羰基进行缩醛化后，得到相应的缩醛8，使用(Ipc)2BH进行不对称化，并通过氧化工序转化为手性醇11，在大多数情况下获得了良好的产率和优异的对映体过量。
• Acylation of Tropane Alkaloids Displaying Reversed Diastereoselectivities under Enzymatic versus Chemical Conditions
  作者：Olena Affolter、Angelika Baro、Sabine Laschat、Peter Fischer

  DOI：10.1515/znb-2007-0112

  日期：2007.1.1

  Lipase-mediated monoacetylation of 6,7-dihydroxytropinones 4 gave acetates 5, ent-5 which were analyzed as Mosher esters 9a, b by ¹H NMR spectroscopy. However, the hydroxy groups in 4 were not differentiated by lipases. Reduction of the keto function and subsequent silylation afforded a mixture of endo/exo-TBS ethers 11, which were dihydroxylated to give the corresponding diols endo/exo-12. In chemical acetylation a change of the endo/exo ratio in favor of the endo-derivative endo-13 was observed, whereas the formation of the exo-acetate exo-13 dominated in lipase-catalyzed acylation reactions. A mechanistic proposal is given.

  使用脂肪酶介导的单乙酰化反应，将6,7-二羟基曲酮4转化为醋酸酯5和ent-5，并通过1H NMR光谱分析其为Mosher酯9a,b。然而，脂肪酶无法区分4中的羟基基团。将酮基还原并随后进行硅基化，得到内/外TBS醚11的混合物，这些醚经过二羟基化反应得到相应的二醇内/外-12。在化学乙酰化反应中，内/外比率向内衍生物endo-13转化，而在脂肪酶催化的乙酰化反应中，exo-13的生成占优势。还提出了一个机理假设。