1-(8-甲基-8-氮杂双环[3.2.1]辛-2-烯-2-基)乙酮 | 137331-57-8

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 1-(8-甲基-8-氮杂双环[3.2.1]辛-2-烯-2-基)乙酮
• 英文名称: 8-Methyl-2-(methylcarbonyl)-8-azabicyclo<3.2.1>oct-2-ene
• 英文别名: 8-methyl-2-(2-methylcarbonyl)-8-azabicyclo[3.2.1]oct-2-ene；(+/-)-ferruginine；N-Methyl-2-acetyl-8-azabicyclo-[3.2.1]oct-2-ene；N-Methyl-2-acetyl-8-azabicyclo[3.2.1]oct-2-ene；Ethanone, 1-(8-methyl-8-azabicyclo[3.2.1]oct-2-en-2-yl)-(9CI)；1-(8-methyl-8-azabicyclo[3.2.1]oct-2-en-2-yl)ethanone
• CAS: 137331-57-8
• 化学式: C₁₀H₁₅NO
• 分子量: 165.235
• InChiKey: KQIRSQYBYQBMIG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.7
• 拓扑面积：
  20.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(8-甲基-8-氮杂双环[3.2.1]辛-2-烯-2-基)乙酮 、 对甲苯基溴化镁 在 copper bromide-dimethyl sulfide 作用下， 以 乙醚 为溶剂， 以55%的产率得到2β-acetyl-8-methyl-3β-p-tolyl-8-azabicyclo<3.2.1>octane
  参考文献：
  名称：

  Synthesis of 2.beta.-Acyl-3.beta.-aryl-8-azabicyclo[3.2.1]octanes and Their Binding Affinities at Dopamine and Serotonin Transport Sites in Rat Striatum and Frontal Cortex

  摘要：

  A novel entry to tropane analogs of cocaine was developed on the basis of the reaction of rhodium-stabilized vinylcarbenoids with pyrroles. These analogs were tested:in binding to dopamine and serotonin (5-HT) transporters in:membranes from rat striatum and frontal cortex. In all the analogs, the aryl group at the 3-position was directly bound to the tropane ring (as in WIN-35,428), and methyl or ethyl ketone moieties were present at the a-position instead of the typical ester group. The series of analogs containing a 2-naphthyl group at the 3-position were most potent, with K-i values < 1 nM in binding to both dopamine and 5-HT transporters. Although the unsubstituted 2-naphthyl analog was nonselective at dopamine and 5-HT transport sites, other compounds:were selective for either site. In general, compounds with relatively small substituents on the aromatic moiety (such as p-methyl or p-fluoro) were relatively selective for the dopamine transporters, while a p-isopropylphenyl derivative was selective:for the 5-HT transport sites. This latter compound represents the first N-methyltropane derivative specific for 5-HT transporters. Resolution of two of the most significant analogs was achieved by HPLC on a chiral stationary phase; the active enantiomer of a 2-naphthyl analog exhibited K-i values of <0.1 nM at both dopamine and 5-HT transporter sites.

  DOI：

  10.1021/jm00035a005
• 作为产物：
  描述：

  3-Diazo-4-penten-2-one 在 RhCl(PPh₃)3 rhodium(II) octanoate 、 四丁基氟化铵 、 氢气 、 sodium cyanoborohydride 作用下， 以 四氢呋喃 、 乙醇 、 水 、 甲苯 、 乙腈 为溶剂， 25.0 ℃ 、310.27 kPa 条件下， 反应 36.25h， 生成 1-(8-甲基-8-氮杂双环[3.2.1]辛-2-烯-2-基)乙酮
  参考文献：
  名称：

  Synthesis of (.+-.)-ferruginine and (.+-.)-anhydroecgonine methyl-ester by a tandem cyclopropanation/Cope rearrangement

  摘要：

  Rhodium(II) acetate catalyzed decomposition of vinyldiazomethanes in the presence of N-(alkoxycarbonyl)pyrroles led to the synthesis of 8-azabicyclo[3.2.1]octa-2,6-dienes. The vinylcarbenoids generated from vinyldiazomethanes with a single electron-withdrawing group exhibited competing reactivity at the vinyl terminus in addition to the carbenoid site. Good regiocontrol was possible, however, by appropriate choice of catalyst and solvent. The practicality of this new approach to tropane alkaloids was demonstrated through short syntheses of (+/-)-ferruginine, (+/-)-anhydroecgonine methyl ester, and the lower homologue of (+/-)-anatoxin a.

  DOI：

  10.1021/jo00019a044

文献信息

• BF₃-Induced Rearrangement of Aziridino Cyclopropanes Derived from 2-Phenylsulfonyl 1,3-Dienes. Application to the Total Synthesis of (±)-Ferruginine
  作者：Sandra Y. Jonsson、Claes M. G. Löfström、Jan-E. Bäckvall

  DOI：10.1021/jo001147b

  日期：2000.12.1

  Total synthesis of the alkaloid (+/-)-ferruginine (1) has been developed via the 2-phenylsulfonyl 1,3-diene approach. BF(3)-induced rearrangement of the N-protected cyclohexane aziridino cyclopropane 8, derived from its corresponding epoxy cyclopropane, afforded the desired tropane alkaloid skeleton 9 in good yield. Michael addition of nitroethane (as an acyl anion equivalent) and transformation of

  已经通过2-苯基磺酰基1，3-二烯方法开发了生物碱（+/-）-铁精氨酸（1）的全合成。BF（3）诱导的N保护的环己烷叠氮基叠氮基环丙烷8的重排衍生自其相应的环氧环丙烷，以高收率提供了所需的托烷生物碱骨架9。迈克尔·迈克尔加成硝基乙烷（以酰基阴离子当量计）并将加合物10的硝基转化为酮基官能团，得到11。除去苯亚磺酸，随后用甲基取代甲苯磺酰基，得到标题化合物1。
• Azabicyclo and azacyclo oxime and amine cholinergic agents and methods
  申请人：Warner-Lambert Company

  公开号：US05346911A1

  公开（公告）日：1994-09-13

  Pharmaceutically useful nitrogen containing cyclic oxime and amine substituted compounds which are azabicyclo[2.2.1]oximes, azabicyclo[2.2.2]oximes, azabicyclo[2.2.1]amines, azabicyclo[2.2.2]amines, azabicyclo[3.2.1]oximes, and amine containing heterocyclic oximes wherein the heterocyclic ring contains from 3 to 7 carbon atoms are disclosed.

  本发明涉及一种在制药方面有用的氮杂环氧胺和胺取代化合物，其中所述化合物包括：azabicyclo[2.2.1]氧杂环己烯、azabicyclo[2.2.2]氧杂环庚烯、azabicyclo[2.2.1]胺、azabicyclo[2.2.2]胺、azabicyclo[3.2.1]氧杂环己烯以及含有胺的杂环氧胺，其中所述杂环环中含有3至7个碳原子。
• Azabicyclo and azacyclo oxime and amine cholinergic agents and pharmaceutically acceptable salts thereof
  申请人：WARNER-LAMBERT COMPANY

  公开号：EP0445731A1

  公开（公告）日：1991-09-11

  Pharmaceutically useful nitrogen containing cyclic oxime and amine substituted compounds of the formula which are azabicyclo[2.2.1]oximes, azabizyclo[2.2.2]oximes, azabicyclo[2.2.1]amines, azabicyclo[2.2.2]amines, azabicyclo[3.2.1]oximes and amine containing heterocyclic oximes wherein the heterocyclic ring contains from 3 to 7 carbon atoms. These compounds are useful as analgesics and for the treatment of cognitive decline in a patient.

  药用含氮环肟和胺取代的式化合物 其中包括氮杂双环[2.2.1]肟、氮杂双环[2.2.2]肟、氮杂双环[2.2.1]胺、氮杂双环[2.2.2]胺、氮杂双环[3.2.1]肟和含胺杂环肟，其中杂环含有 3 至 7 个碳原子。这些化合物可用作镇痛剂和治疗患者认知能力下降。
• US5306718A
  申请人：——

  公开号：US5306718A

  公开（公告）日：1994-04-26
• US5346911A
  申请人：——

  公开号：US5346911A

  公开（公告）日：1994-09-13