(-)-epiquinamide | 885111-38-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹嗪类
• 英文名称: (-)-epiquinamide
• 英文别名: (1R,9aR)-Epiquinamide；(1R*,10R*)-1-Acetamidoquinolizidine；N-[(1R,9aR)-2,3,4,6,7,8,9,9a-octahydro-1H-quinolizin-1-yl]acetamide
• CAS: 885111-38-6
• 化学式: C₁₁H₂₀N₂O
• 分子量: 196.293
• InChiKey: ZFOJLLQHJIXKHO-GHMZBOCLSA-N

物化性质

• 熔点：
  122-123 °C(Solv: ethyl acetate (141-78-6); ligroine (8032-32-4))
• 沸点：
  363.0±21.0 °C(Predicted)
• 密度：
  1.05±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (-)-epiquinamide 在 盐酸 作用下， 以 乙醚 为溶剂， 生成 N-((1R,9aR)-octahydro-2H-quinolizin-1-yl)acetamide hydrochloride
  参考文献：
  名称：

  Epiquinamide: A Poison That Wasn’t from a Frog That Was

  摘要：

  In 2003, we reported the isolation, structure elucidation, and pharmacology of epiquinamide (1), a novel alkaloid isolated from an Ecuadoran poison frog, Epipedobates tricolor. Since then, several groups, including ours, have undertaken synthetic efforts to produce this compound, which appeared initially to be a novel, beta 2-selective nicotinic acetylcholine receptor agonist. Based on prior chiral GC analysis of synthetic and natural samples, the absolute structure of this alkaloid was established as (1S,9aS)-1-acetamidoquinolizidine. We have synthesized the (1R*,9aS*)-isomer (epi-epiquinamide) using an iminium ion nitroaldol reaction as the key step. We have also synthesized ent-1 semisynthetically from (-)-lupinine. Synthetic epiquinamide is inactive at nicotinic receptors, in accord with recently published reports. We have determined that the activity initially reported is due to cross-contamination from co-occurring epibatidine in the isolated material.

  DOI：

  10.1021/np8005452
• 作为产物：
  描述：

  N^α-Z-N^δ-Boc-D-Orn-OMe 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 palladium on activated charcoal 4-二甲氨基吡啶 、 sodium hydroxide 、 氢气 、 potassium carbonate 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium tri-t-butoxyaluminum hydride 、 三乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 乙醚 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 77.33h， 生成 (-)-epiquinamide
  参考文献：
  名称：

  表喹酰胺对映异构体的实用的全合成。

  摘要：

  表喹酰胺及其对映异构体的短而实用的合成是从容易获得的起始原料中以较高的总收率和较高的立体选择性完成的。

  DOI：

  10.1021/ol061736p

文献信息

• Divergent Method to <i>trans</i>-5-Hydroxy-6-alkynyl/alkenyl-2-piperidinones: Syntheses of (−)-Epiquinamide and (+)-Swainsonine
  作者：Chang-Mei Si、Zhuo-Ya Mao、Han-Qing Dong、Zhen-Ting Du、Bang-Guo Wei、Guo-Qiang Lin

  DOI：10.1021/acs.joc.5b00803

  日期：2015.6.5

  An efficient diastereoselective approach to access trans-5-hydroxy-6-alkynyl/alkenyl-2-piperidinones has been developed through nucleophilic addition of α-chiral aldimines using alkynyl/alkenyl Grignard reagents. The diastereoselectivity of alkenyl in C-6 position of 2-piperidinone was controlled by α-alkoxy substitution, while the alkynyl was controlled by the coordination of the α-alkoxy substitution

  通过使用炔基/烯基格利雅试剂试剂亲核加成α-手性醛亚胺，已经开发了一种有效的非对映选择性方法，可用于反式-5-羟基-6-炔基/烯基-2-哌啶酮。α-烷氧基取代控制2-哌啶酮C-6位置链烯基的非对映选择性，而α-烷氧基取代和亚磺酰胺的立体化学则控制炔基。（-）-表喹酰胺和（+）-swainsonine的不对称合成证明了这种简单的级联过程的实用性。
• Stereoflexible total synthesis of (−)-epiquinamide
  作者：S. Chandrasekhar、Bibhuti Bhusan Parida、Ch. Rambabu

  DOI：10.1016/j.tetlet.2009.02.051

  日期：2009.7

  Hydroxy propiolate rearrangement to conjugated diene, Sharpless asymmetric dihydroxylation and one-pot quinolizine construction have been used as key steps in the total synthesis of (−)-epiquinamide.

  羟基丙酸酯重排至共轭二烯，Sharpless不对称二羟基化反应和一锅喹诺嗪结构已被用作（-）-表喹酰胺全合成的关键步骤。
• [EN] PREPARATION OF PHANTASMIDINE AND ANALOGUES THEREOF<br/>[FR] PRÉPARATION DE PHANTASMIDINE ET DE SES ANALOGUES
  申请人：UNIV BRANDEIS

  公开号：WO2012078608A1

  公开（公告）日：2012-06-14

  Described are methods of synthesizing phantasmidine and analogues thereof from commercially available starting materials. The compounds are useful as pharmacological probes and potential lead compounds for the development of selective nicotinic receptor therapeutics.

  描述了从商业可获得的起始物质中合成幻影啉及其类似物的方法。这些化合物可用作药理学探针，也可作为选择性尼古丁受体治疗药物开发的潜在先导化合物。
• Short Total Synthesis of (-)-Lupinine and (-)-Epiquinamide by Double Mitsunobu Reaction
  作者：Leonardo Santos、Yaneris Mirabal-Gallardo、Nagula Shankaraiah、Mario Simirgiotis

  DOI：10.1055/s-0030-1258356

  日期：2011.1

  (-)-epiquinamide (2) have been described via the key intermediate 3 obtained from the addition of 2-trialkylsilyloxyfuran 5 to N-acyliminium intermediate derived from 4. The major R,R-isomer 8 obtained from the Mannich reaction was converted into its R,S-isomer through Mitsunobu reaction. Then, a second Mitsunobu reaction of 3 led to cyano 9 and azido 11 derivatives, which were converted into 1 and 2 in 33 and

  （-）-羽扇豆碱（1）和（-）-表喹酰胺（2）的替代总合成物已通过关键中间体3进行了描述，该中间体是将2-三烷基甲硅烷基氧基呋喃5加到由4衍生的N-酰基亚胺中间产物而获得的。由曼尼希反应获得的主要的R，R-异构体8通过Mitsunobu反应转化为它的R，S-异构体。然后，第二次3的Mitsunobu反应导致了氰基9和叠氮基11衍生物，它们被转化为1和分别占33％和2％的产率（来自4）。合成途径适合于产生几种喹诺唑烷生物碱。 喹喔啉生物碱-叠氮基还原-硼化镍-微波辐射-Mitsunobu反应
• A new approach to asymmetric synthesis of (−)-epiquinamide from d-glucose
  作者：Kanyapat Lumyong、Boonsong Kongkathip、Nutthawat Chuanopparat、Ngampong Kongkathip

  DOI：10.1016/j.tet.2018.12.045

  日期：2019.1

  The asymmetric total synthesis of (−)-epiquinamide has been achieved starting from a 5-iodofuranoside synthon derived from d-glucose. The methods featured Bernet-Vasella reaction followed by Horner-Wadsworth-Emmons (HWE) reaction to provide a new chiral building block diene as the key steps. The bicyclic framework of this quinolizidine was constructed by selective reduction of α,β-unsaturated ester

  的不对称全合成（ - ） - epiquinamide已经实现从衍生自5- iodofuranoside合成子起始d -葡萄糖。该方法的特色是Bernet-Vasella反应，然后进行Horner-Wadsworth-Emmons（HWE）反应，以提供一种新的手性结构单元二烯作为关键步骤。通过选择性还原α，β-不饱和酯，分子内亲核取代和闭环易位，构建了该喹喔啉的双环骨架。