N-methoxycarbonylcytisine | 125109-97-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 羽扇豆生物碱
• 英文名称: N-methoxycarbonylcytisine
• 英文别名: (-)-N-methoxycarbonyl-1,2,3,4,5,6-hexahydro-1,5-methano-pyrido[1,2-a][1,5]diazocin-8-one；(-)-methyl (1R,9S)-6-oxo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-diene-11-carboxylate；(1R,5S)-1,5,6,8-tetrahydro-8-oxo-1,5-methano-2H-pyrido[1,2-a][1,5]diazocine-3(4H)-carboxylic acid methyl ester；(1R,5S)-N-Methoxycarbonyl-1,2,3,4,5,6-hexahydro-1,5-methanopyrido-[1,2-a][1,5]diazocin-8-one (-)-2；methyl (1R,9R)-6-oxo-7,11-diazatricyclo[7.3.1.02,7]trideca-2,4-diene-11-carboxylate
• CAS: 125109-97-9
• 化学式: C₁₃H₁₆N₂O₃
• 分子量: 248.282
• InChiKey: XPJCPQOVGUMVLU-VHSXEESVSA-N

物化性质

• 沸点：
  464.8±44.0 °C(Predicted)
• 密度：
  1.32±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  49.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-methoxycarbonylcytisine 在 lithium chloride 水 、 氯化铵 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 3.5h， 以79%的产率得到6α-methoxycarbonylcytisine
  参考文献：
  名称：

  Regio- and diastereoselective functionalization of (−)-cytisine: an unusual N–C acyl migration

  摘要：

  In order to test (-)-cytisine as a potential chiral inductor, N-propionyl cytisine was treated with LDA and then with benzyl bromide. Instead of the expected alpha-benzyl substituted propionamide, (-)-N-benzyl 6alpha-propionyl cytisine was formed, arising from an unusual diastereoselective nitrogen to carbon acyl migration. Using LDA in the presence of an excess of LiCl, the 6-substituted cytisine was isolated in yields of up to 79%. The efficiency of the N-C acyl transfer was shown to be dependent on the nature of the N-acyl group. Complete epimerization of the newly created stereocenter was observed under basic conditions. This methodology allows the stereoelective functionalization of the C-6 position of cytisine, an important agonist of nicotinic receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(02)00271-9
• 作为产物：
  描述：

  氯甲酸甲酯 、 cytisine 生成 N-methoxycarbonylcytisine
  参考文献：
  名称：

  在 O-烷基氨基甲酸酯的对映选择性锂化-亲电捕获中评价类斯巴丁手性二胺

  摘要：

  在二胺介导的 O-烷基氨基甲酸酯的不对称锂化捕获中评估了七种 (+)-sparteine 样二胺和 (-)-sparteine。(+)-sparteine 样二胺（手性位移 NMR 光谱≥98:2 er）由 (-)-金雀花碱（N-苄基金雀花碱的手性 HPLC 得到 >99:1 er）和两个新的 (+)含有 N-CD3 取代基的类sparteine 二胺被包括在本研究中。从配体评估研究中获得了以下结果： (-)-sparteine 在诱导近乎完美的对映选择性 (99 : 1 er) 的能力方面无与伦比；N-甲基二胺和两种 N-CD3-取代的二胺是最佳的 (+)-sparteine 替代物（高达 96 : 4 er）；空间位阻更大的 N-烷基取代基降低了对映选择性（N-异丙基：86：14 er；N-CH2tBu：54：46 er）。从合成的角度来看，

  DOI：

  10.1039/b600032k

文献信息

• 5-Substituted Derivatives of the Tricyclic (+)-Sparteine Surrogate in the Enantioselective Lithiation/Stannylation of an<i>O</i>-Alkyl Carbamate
  作者：Matthias Breuning、David Hein

  DOI：10.1002/ejoc.201300987

  日期：2013.11

  5-Mono- and 5,5-disubstituted tricyclic bispidines, derivatives of the known (+)-sparteine surrogate, have been synthesized in four-to-six steps from the natural alkaloid (–)-cytisine and evaluated as chiral ligands in the enantioselective lithiation/stannylation of an O-alkyl carbamate. Structure–selectivity studies revealed that a small 5-endo substituent is tolerated, whereas larger 5-endo substituents

  5-单和 5,5-二取代的三环双吡啶是已知 (+)-sparteine 替代物的衍生物，已从天然生物碱 (-)-cytisine 以四到六个步骤合成，并被评估为手性配体O-烷基氨基甲酸酯的对映选择性锂化/甲锡烷基化。结构选择性研究表明，可以耐受较小的 5-endo 取代基，而较大的 5-endo 取代基甚至较小的 5-exo 取代基会导致手性转移水平显着降低。
• SYNTHESIS OF (+)-(1R,2S,9S)-11-METHYL-7,11-DIAZATRICYCLO[7.3.1.02,7]TRIDECANE, A (+)-SPARTEINE SURROGATE
  作者：Dixon, Amanda J.、McGrath, Matthew J.、O’Brien, Peter、Holle, Sigrid、Fürstner, Alois

  DOI：10.15227/orgsyn.083.0141

  日期：——
• Synthesis of Analogues of (−)-Cytisine for in Vivo Studies of Nicotinic Receptors Using Positron Emission Tomography
  作者：Eddie Marrière、Jacques Rouden、Vincent Tadino、Marie-Claire Lasne

  DOI：10.1021/ol005685m

  日期：2000.4.1

  9-Substituted analogues of (-)-cytisine were synthesized in high yields via palladium-mediated couplings of either 9- (-)-bromocytisine and organostannanes or 9-(-) trimethylstannylcytisine and fluorobromobenzene. The protection of the amine with a nitroso group and the use of PdCl2(PPh3)(2) to carry out the Stille reaction allowed the rapid synthesis of 9-(4'-[F-18]fluorophenyl)cytisine (F-18: t(1/2) = 109.7 min), a new promising radioligand (radiochemical yield: 10% from [F-18]KF, 150 min, four steps) for positron emission tomography studies of alpha(4)beta(2) nicotinic receptors.
• Regio- and diastereoselective functionalization of (−)-cytisine: an unusual N–C acyl migration
  作者：Jacques Rouden、Alexis Ragot、Sonia Gouault、Dominique Cahard、Jean-Christophe Plaquevent、Marie-Claire Lasne

  DOI：10.1016/s0957-4166(02)00271-9

  日期：2002.7

  In order to test (-)-cytisine as a potential chiral inductor, N-propionyl cytisine was treated with LDA and then with benzyl bromide. Instead of the expected alpha-benzyl substituted propionamide, (-)-N-benzyl 6alpha-propionyl cytisine was formed, arising from an unusual diastereoselective nitrogen to carbon acyl migration. Using LDA in the presence of an excess of LiCl, the 6-substituted cytisine was isolated in yields of up to 79%. The efficiency of the N-C acyl transfer was shown to be dependent on the nature of the N-acyl group. Complete epimerization of the newly created stereocenter was observed under basic conditions. This methodology allows the stereoelective functionalization of the C-6 position of cytisine, an important agonist of nicotinic receptors. (C) 2002 Elsevier Science Ltd. All rights reserved.
• Evaluation of sparteine-like chiral diamines in the enantioselective lithiation–electrophilic trapping of an O-alkyl carbamate
  作者：Cédric Genet、Matthew J. McGrath、Peter O'Brien

  DOI：10.1039/b600032k

  日期：——

  Seven (+)-sparteine-like diamines and (−)-sparteine were evaluated in the diamine-mediated asymmetric lithiation–trapping of an O-alkyl carbamate. The (+)-sparteine-like diamines (≥98 : 2 er by chiral shift NMR spectroscopy) were prepared from (−)-cytisine (>99 : 1 er by chiral HPLC of N-benzyl cytisine) and two new (+)-sparteine-like diamines containing N-CD3 substituents were included as part of

  在二胺介导的 O-烷基氨基甲酸酯的不对称锂化捕获中评估了七种 (+)-sparteine 样二胺和 (-)-sparteine。(+)-sparteine 样二胺（手性位移 NMR 光谱≥98:2 er）由 (-)-金雀花碱（N-苄基金雀花碱的手性 HPLC 得到 >99:1 er）和两个新的 (+)含有 N-CD3 取代基的类sparteine 二胺被包括在本研究中。从配体评估研究中获得了以下结果： (-)-sparteine 在诱导近乎完美的对映选择性 (99 : 1 er) 的能力方面无与伦比；N-甲基二胺和两种 N-CD3-取代的二胺是最佳的 (+)-sparteine 替代物（高达 96 : 4 er）；空间位阻更大的 N-烷基取代基降低了对映选择性（N-异丙基：86：14 er；N-CH2tBu：54：46 er）。从合成的角度来看，