5'-cyanonicotine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 5'-cyanonicotine
• 英文别名: (5S)-1-methyl-5-pyridin-3-ylpyrrolidine-2-carbonitrile
• 化学式: C₁₁H₁₃N₃
• 分子量: 187.244
• InChiKey: DUKKSGGNSSFORH-DTIOYNMSSA-N

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：
  0.45
• 拓扑面积：
  39.9
• 氢给体数：
  0
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  烟碱	nicotin	54-11-5	C10H14N2	162.235
  (+/-)-尼古丁	3-(1-methyl-pyrrolidin-2-yl)-pyridine	22083-74-5	C10H14N2	162.235
  吡啶吡咯酮	cotinine	486-56-6	C10H12N2O	176.218

反应信息

• 作为反应物：
  描述：

  5'-cyanonicotine 在 高氯酸 作用下， 以 乙醇 为溶剂， 生成 (S)-nicotine Δ-^1',5'-iminium bisperchlorate
  参考文献：
  名称：

  Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)-nicotine to the (S)-nicotine .DELTA.1'(5')-iminium species

  摘要：

  Mammals metabolize the tobacco alkaloid (S)-nicotine primarily to the lactam (S)-cotinine by a pathway involving an initial cytochrome P-450 catalyzed two-electron oxidation at the prochiral 5'-carbon atom. The stereochemical course of this oxidation was examined with human microsomal preparations and the E and Z diastereomers of (S)-nicotine-5'd1. The metabolically generated delta 1'(5')-iminium ion intermediate was trapped and analyzed as the corresponding diastereomeric 5'-cyano derivatives by a capillary column GC-EIMS selected ion monitoring assay. The results of these studies established that this biotransformation proceeds with the stereoselective abstraction of the 5'-pro-E proton, that is, the C-5' proton trans to the bulky pyridyl group. The observed stereoselectivity was independent of proton vs. deuteron abstraction. Additionally, the extent of (S)-cotinine formation was minor and did not influence the stereochemical composition of the metabolically derived alpha-cyano amines. Studies with male Dutch rabbit liver microsomal preparations gave similar results. These findings suggest that the structure of the complex formed between (S)-nicotine and the active site of cytochrome P-450 is highly ordered and dictates the stereochemical course of the reaction pathway.

  DOI：

  10.1021/jm00385a004
• 作为产物：
  描述：

  吡啶吡咯酮 在 溶剂黄146 、 红铝 作用下， 以 乙醚 、 水 为溶剂， 反应 3.0h， 生成 5'-cyanonicotine
  参考文献：
  名称：

  Stereochemical studies on the cytochrome P-450 catalyzed oxidation of (S)-nicotine to the (S)-nicotine .DELTA.1'(5')-iminium species

  摘要：

  Mammals metabolize the tobacco alkaloid (S)-nicotine primarily to the lactam (S)-cotinine by a pathway involving an initial cytochrome P-450 catalyzed two-electron oxidation at the prochiral 5'-carbon atom. The stereochemical course of this oxidation was examined with human microsomal preparations and the E and Z diastereomers of (S)-nicotine-5'd1. The metabolically generated delta 1'(5')-iminium ion intermediate was trapped and analyzed as the corresponding diastereomeric 5'-cyano derivatives by a capillary column GC-EIMS selected ion monitoring assay. The results of these studies established that this biotransformation proceeds with the stereoselective abstraction of the 5'-pro-E proton, that is, the C-5' proton trans to the bulky pyridyl group. The observed stereoselectivity was independent of proton vs. deuteron abstraction. Additionally, the extent of (S)-cotinine formation was minor and did not influence the stereochemical composition of the metabolically derived alpha-cyano amines. Studies with male Dutch rabbit liver microsomal preparations gave similar results. These findings suggest that the structure of the complex formed between (S)-nicotine and the active site of cytochrome P-450 is highly ordered and dictates the stereochemical course of the reaction pathway.

  DOI：

  10.1021/jm00385a004

文献信息

• A Highly Active System for the Metal-Free Aerobic Photocyanation of Tertiary Amines with Visible Light: Application to the Synthesis of Tetraponerines and Crispine A
  作者：Julio Cesar Orejarena Pacheco、Alexander Lipp、Alexander M. Nauth、Fabian Acke、Jule-Philipp Dietz、Till Opatz

  DOI：10.1002/chem.201504845

  日期：2016.4.4

  A highly efficient metal‐free catalytic system for the aerobic photocyanation of tertiary amines with visible light is reported. The use of air as terminal oxidant offers an improved safety profile compared with pure oxygen, the used compact fluorescent lamp (CFL) light sources are highly economical, and no halogenated solvents are required. This system not only proves to be effective for a wide variety

  报道了一种高效的无金属催化体系，用于可见光下叔胺的有氧光致氰化。与纯氧相比，使用空气作为终端氧化剂可提高安全性，所使用的紧凑型荧光灯（CFL）光源非常经济，并且不需要卤化溶剂。该系统不仅证明对多种三烷基胺，药物和生物碱有效，而且显着还使有机染料有史以来最低的催化剂负载量（0.00001 mol％或0.1 ppm）。对获得的α-氨基腈进行了Bruylants反应和C-烷基化/脱氰，以证明复杂分子的后功能化。
• Graphene oxide and Rose Bengal: oxidative C–H functionalisation of tertiary amines using visible light
  作者：Yuanhang Pan、Shuai Wang、Choon Wee Kee、Emilie Dubuisson、Yuanyong Yang、Kian Ping Loh、Choon-Hong Tan

  DOI：10.1039/c1gc15865a

  日期：——

  Visible light induced oxidative C–H functionalisation of tertiary amines catalysed by the combination of graphene oxide and Rose Bengal was developed. This reaction avoids the use of stoichiometric amounts of peroxy compounds as terminal oxidants. This reaction is useful for tri-alkyl amines including chiral tertiary amines. Both cyanide and trifluoromethyl nucleophiles were shown to participate in this reaction, providing α-cyano- and α-trifluoromethylated tertiary amines.

  在氧化石墨烯和玫瑰红的共同催化下，开发了可见光诱导的叔胺氧化 CâH 功能化。该反应避免了使用过氧化合物作为末端氧化剂。该反应适用于包括手性叔胺在内的三烷基胺。氰化物和三氟甲基亲核物均可参与该反应，提供δ-氰基和δ-三氟甲基化叔胺。
• NICOTINE COMPOUNDS AND ANALOGS THEREOF, SYNTHETIC METHODS OF MAKING COMPOUNDS, AND METHODS OF USE
  申请人：Kem William Reade

  公开号：US20130157995A1

  公开（公告）日：2013-06-20

  Embodiments of the present disclosure provide for compounds such as those shown in FIG. 1.1 (compounds A, B, C, and D), 2′substituted nicotine compounds, azetidine compounds, ether linked nicotine compounds (FIG. 1.2 , compounds E, F, G, and H), methods of synthesis of the compounds, methods of treatment of a condition using compounds A, B, C, D, 2′substituted nicotine compounds, azetidine compounds, or ether linked nicotine compounds, methods of selectively stimulating alpha7 nAChR and/or alpha4beta2 receptors, and the like.

  本公开的实施例提供了化合物，例如图1.1所示的化合物A、B、C和D，2'取代尼古丁化合物，氮杂环化合物，以太键结合的尼古丁化合物（图1.2，化合物E、F、G和H），化合物的合成方法，使用化合物A、B、C、D、2'取代尼古丁化合物、氮杂环化合物或以太键结合的尼古丁化合物治疗疾病的方法，选择性刺激α7 nAChR和/或α4beta2受体的方法等。
• Nicotinic attenuation of CNS inflammation and autoimmunity
  申请人：DIGNITY HEALTH

  公开号：US10080747B2

  公开（公告）日：2018-09-25

  The present invention relates to methods of treating and/or ameliorating the severity of inflammation and autoimmunity in the central nervous system (CNS). In one embodiment, the present invention provides a method of treating multiple sclerosis by administering a therapeutically effective dosage of nicotine, or a pharmaceutical equivalent, analog, derivative, or salt thereof.

  本发明涉及治疗和/或改善中枢神经系统（CNS）炎症和自身免疫严重程度的方法。在一个实施方案中，本发明提供了一种通过施用治疗有效剂量的尼古丁或其药物等效物、类似物、衍生物或盐来治疗多发性硬化症的方法。
• LIPOPHILIC ACTIVE AGENT INFUSED COMPOSITIONS WITH REDUCED FOOD EFFECT
  申请人：Poviva Corp.

  公开号：EP3780976A1

  公开（公告）日：2021-02-24