(1R,5S)-2-acetyl-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene | 172277-49-5

• 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: (1R,5S)-2-acetyl-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene
• 英文别名: (1R,5S)-2-acetyl-8-(tert-butoxycarbonyl)-8-azabicyclo<3.2.1>-2-octene；(1R,5S)-2-acetyl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylic acid tert-butyl ester；(-)-(1R,5S)-N-Boc-norferruginine；tert-butyl (1R,5S)-2-acetyl-8-azabicyclo[3.2.1]oct-2-ene-8-carboxylate
• CAS: 172277-49-5
• 化学式: C₁₄H₂₁NO₃
• 分子量: 251.326
• InChiKey: VNFKXJBTBWRZAD-ZYHUDNBSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 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：

  (1R,5S)-2-acetyl-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene 在 sodium cyanoborohydride 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 生成 (-)-Ferruginine
  参考文献：
  名称：

  Enantiospecific Synthesis of (+)- and (−)-Ferruginine from l-Glutamic Acid. Synthesis of Tropanes via Intramolecular Iminium Ion Cyclization

  摘要：

  Iminium ions, generated by decarbonylation of N-benzyl-5-[1-(methoxycarbonyl)-4-oxopentyl]-prolines, prolines, undergo intramolecular cyclization to afford 2,4-disubstituted tropanes in good yields. This transformation is also shown to be a stereospecific reaction. The value of these substituted tropanes has been demonstrated by functional group manipulation, leading to the enantiospecific synthesis of (+)-ferruginine, an alkaloid isolated from Darlinga ferruginea, and its unnatural enantiomer, (-)-ferruginine.

  DOI：

  10.1021/jo9515081
• 作为产物：
  描述：

  endo-8-azabicyclo[3.2.1]octane-2,8-dicarboxylic acid 8-tert-butyl ester 2-methyl ester 在 氢氧化钾 、 sodium periodate 、 苯基氯化硒 、 甲基锂 、 三乙胺 、 lithium diisopropyl amide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醚 、 异丙醇 为溶剂， 反应 42.58h， 生成 (1R,5S)-2-acetyl-8-<(1,1-dimethylethoxy)carbonyl>-8-azabicyclo<3.2.1>octa-2-ene
  参考文献：
  名称：

  Enantiospecific Synthesis of (+)- and (−)-Ferruginine from l-Glutamic Acid. Synthesis of Tropanes via Intramolecular Iminium Ion Cyclization

  摘要：

  Iminium ions, generated by decarbonylation of N-benzyl-5-[1-(methoxycarbonyl)-4-oxopentyl]-prolines, prolines, undergo intramolecular cyclization to afford 2,4-disubstituted tropanes in good yields. This transformation is also shown to be a stereospecific reaction. The value of these substituted tropanes has been demonstrated by functional group manipulation, leading to the enantiospecific synthesis of (+)-ferruginine, an alkaloid isolated from Darlinga ferruginea, and its unnatural enantiomer, (-)-ferruginine.

  DOI：

  10.1021/jo9515081

文献信息

• Total Synthesis of (−)-Cocaine and (−)-Ferruginine
  作者：Guolin Cheng、Xinyan Wang、Rui Zhu、Changwei Shao、Jimin Xu、Yuefei Hu

  DOI：10.1021/jo200069m

  日期：2011.4.15

  synthesis of tropane alkaloids (−)-cocaine and (−)-ferruginine were accomplished in nine steps each and in 55% and 46% overall yields, respectively, starting from the known Betti base derivative (+)-(7aR,10R,12S)-10-(1H-benzotriazol-1-yl)-7a,8,9,10-tetrahydro-12-phenyl-12H-naphtho[1,2-e]pyrrolo[2,1-b][1,3]oxazine. In this novel route, RCM reaction and 1,3-dipolar cycloaddition were employed as key steps

  从已知的Betti基础衍生物（+）-（7a R，10 R，12 S）-10-（1 H-苯并三唑-1-基）-7a，8,9,10-四氢-12-苯基-12 H-萘[1,2- e ]吡咯并[2,1- b ] [1,3]恶嗪。在该新颖途径中，RCM反应和1，3-偶极环加成被用作对映烷骨架的对映选择性构建和3-溴-2-异恶唑啉环的区域选择性引入作为掩蔽的顺式-2，3-二取代基的关键步骤。获得所需的前体（2 S，5R）-2-烯丙基-5-乙烯基吡咯烷用于RCM反应，我们开发了一种通用且实用的方法，用于制备带有烯键和/或炔烃取代基的对映体纯的顺式-2,5-二取代的吡咯烷。我们还提供了两种高效的途径，可将3-溴-2-异恶唑啉环转化为（-）-可卡因和（-）-铁精氨酸中所需的顺式-2,3-二取代基。
• Formal Synthesis of (+)- and (–)-Ferruginine
  作者：Riccardo Piccardi、Philippe Renaud

  DOI：10.1002/ejoc.200700427

  日期：2007.10

  commercially available tropinone is reported. The desymmetrization of tropinone was achieved through formation of diastereomeric unsaturated sulfoxides using the Andersen procedure. Introduction of the acetyl C(2) side chain was achieved by conjugate addition of lithiated ethyl vinyl ether to an unsaturated sulfone. N-Boc-Norferruginine, an advanced intermediate for the synthesis of ferruginine, was prepared

  据报道，从市售的托品酮开始，天然存在的 (+)-铁蛋白及其对映异构体的正式合成。托品酮的去对称化是通过使用安德森程序形成非对映异构不饱和亚砜来实现的。乙酰基 C(2) 侧链的引入是通过将锂化乙基乙烯基醚共轭添加到不饱和砜来实现的。N-Boc-Norferruginine 是一种用于合成铁蛋白碱的高级中间体，分六步制备，总产率为 19%。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)
• Enantioselective Synthesis of Functionalized Tropanes by Rhodium(II) Carboxylate-Catalyzed Decomposition of Vinyldiazomethanes in the Presence of Pyrroles
  作者：Huw M. L. Davies、Julius J. Matasi、L. Mark Hodges、Nicholas J. S. Huby、Craig Thornley、Norman Kong、Jeffrey H. Houser

  DOI：10.1021/jo961920w

  日期：1997.2.1

  A series of enantiomerically enriched tropanes was synthesized by the rhodium(II) octanoate-catalyzed reaction of various N-BOC-protected pyrroles with vinyldiazomethanes. The overall 3 + 4 annulation occurs by a tandem cyclopropanation/Cope rearrangement. Asymmetric induction was best achieved in these transformations by using either (S)-lactate or (R)-pantolactone as a chiral auxiliary on the vinyldiazomethanes. Reactions carried out with the chiral catalyst tetrakis[N-( 4-tert-butylbenzenesulfonyl)-(L)-prolinato]dirhodium (2) provided moderate asymmetric induction, but also resulted in the formation of isomeric azabicyclooctane side products. The utility of the synthetic process was demonstrated through the asymmetric synthesis of(-)-anhydroecgonine methyl ester and (-)-ferruginine.