(1-carbobenzyloxy-2(S)-pyrrolidynyl)oxirane | 623938-32-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (1-carbobenzyloxy-2(S)-pyrrolidynyl)oxirane
• 英文别名: (2S)-phenylmethyl 2-(oxiran-2-yl)pyrrolidine-1-carboxylate；(RS,S)-(1-carbobenzyloxy-2-pyrrolidinyl)oxirane；benzyl (2S)-2-(oxiran-2-yl)pyrrolidine-1-carboxylate
• CAS: 623938-32-9
• 化学式: C₁₄H₁₇NO₃
• 分子量: 247.294
• InChiKey: VQVQKTLIXHDXCW-UEWDXFNNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.19
• 重原子数：
  18.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  42.07
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (1-carbobenzyloxy-2(S)-pyrrolidynyl)oxirane 在 盐酸 、 lithium aluminium tetrahydride 、 对甲苯磺酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 异丙醇 为溶剂， 反应 24.0h， 生成 (S)-1,1-Dimethyl-2-((2R,5R)-2-methyl-[1,3]oxathiolan-5-yl)-pyrrolidinium; iodide
  参考文献：
  名称：

  Synthesis and cholinergic affinity of diastereomeric and enantiomeric isomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)- pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and of Their iodomethylates

  摘要：

  Four out of the eight possible stereoisomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2methyl-1.3-oxathiolan-5-,I)pyrrolidine and the corresponding iodomethylates have been synthesised. They were formally derived from hybridisation of potent though unselective agonists studied before, such as 1,3-dioxolane 1 and 1,3-oxathiolane 2, with the structure of nicotine. It was expected that, by exalting the molecular complexity of the parent compounds, in particular through stereochemical complication in the proximity of the critical cationic head of the molecule, the chance to find agonists able to discriminate among cholinergic receptors subtypes would increase. The relative and absolute configuration of the compounds obtained has been established by means of NMR spectroscopy and X-ray crystallography. In preliminary studies, their binding affinity has been evaluated on rat brain nicotinic and muscarinic receptors. While none of the compounds showed any nicotinic affinity up to the dose of 10 muM, most of the iodomethylates were endowed with promising affinity for the muscarinic receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00236-0
• 作为产物：
  描述：

  (2S)-(-)-phenylmethyl 2-vinylpyrrolidine-1-carboxylate 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以90%的产率得到(1-carbobenzyloxy-2(S)-pyrrolidynyl)oxirane
  参考文献：
  名称：

  Synthesis and cholinergic affinity of diastereomeric and enantiomeric isomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)- pyrrolidine, 1-methyl-2-(2-methyl-1,3-oxathiolan-5-yl)pyrrolidine and of Their iodomethylates

  摘要：

  Four out of the eight possible stereoisomers of 1-methyl-2-(2-methyl-1,3-dioxolan-4-yl)pyrrolidine, 1-methyl-2-(2methyl-1.3-oxathiolan-5-,I)pyrrolidine and the corresponding iodomethylates have been synthesised. They were formally derived from hybridisation of potent though unselective agonists studied before, such as 1,3-dioxolane 1 and 1,3-oxathiolane 2, with the structure of nicotine. It was expected that, by exalting the molecular complexity of the parent compounds, in particular through stereochemical complication in the proximity of the critical cationic head of the molecule, the chance to find agonists able to discriminate among cholinergic receptors subtypes would increase. The relative and absolute configuration of the compounds obtained has been established by means of NMR spectroscopy and X-ray crystallography. In preliminary studies, their binding affinity has been evaluated on rat brain nicotinic and muscarinic receptors. While none of the compounds showed any nicotinic affinity up to the dose of 10 muM, most of the iodomethylates were endowed with promising affinity for the muscarinic receptors. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00236-0

文献信息

• Synthesis and α4β2 nicotinic affinity of unichiral 5-(2-pyrrolidinyl)oxazolidinones and 2-(2-pyrrolidinyl)benzodioxanes
  作者：Marco Pallavicini、Barbara Moroni、Cristiano Bolchi、Antonio Cilia、Francesco Clementi、Laura Fumagalli、Cecilia Gotti、Fiorella Meneghetti、Loredana Riganti、Giulio Vistoli、Ermanno Valoti

  DOI：10.1016/j.bmcl.2006.08.020

  日期：2006.11

  candidate nicotinoids. One of the two benzodioxane stereoisomers reasonably fits the pharmacophore elements of (S)-nicotine and binds at alpha4beta2 nicotinic acetylcholine receptor with submicromolar affinity. Interestingly, both the synthesized pyrrolidinylbenzodioxanes exhibit analogous affinity at alpha(2) adrenergic receptor resembling the behaviour of some known alpha(2)-AR ligands recently proved to

  合成了分别在5-和2-位带有2-吡咯烷基取代基的2-恶唑烷酮和1,4-苯并二恶烷的RS和SR对映体，作为候选烟碱类化合物。两种苯并二恶烷立体异构体之一合理地适合（S）-尼古丁的药效团元素，并以亚微摩尔亲和力结合在α4beta2烟碱型乙酰胆碱受体上。有趣的是，两个合成的吡咯烷基苯并二恶烷在α（2）肾上腺素能受体上都表现出相似的亲和力，类似于一些最近被证明具有神经元烟碱亲和力的已知α（2）-AR配体的行为。
• 5-(2-Pyrrolidinyl)oxazolidinones and 2-(2-pyrrolidinyl)benzodioxanes: Synthesis of all the stereoisomers and α4β2 nicotinic affinity
  作者：Marco Pallavicini、Cristiano Bolchi、Matteo Binda、Antonio Cilia、Francesco Clementi、Rossana Ferrara、Laura Fumagalli、Cecilia Gotti、Milena Moretti、Alessandro Pedretti、Giulio Vistoli、Ermanno Valoti

  DOI：10.1016/j.bmcl.2008.12.002

  日期：2009.2

  The four stereoisomers of 2-oxazolidinone 5-substituted with 1-methyl-2-pyrrolidinyl (1), of 1,4-benzodioxane 2-substituted with the same residue (2) and of the nor-methyl analogue of this latter (2a) were synthesized as candidate nicotinoids. Of the 12 compounds, two N-methylated pyrrolidinyl-benzodioxane stereoisomers, namely those with the same relative configuration at the pyrrolidine stereocentre as (S)-nicotine, bind at alpha 4 beta 2 nicotinic acetylcholine receptor with submicromolar affinity. Consistently with the biological data, docking analysis enlightens significant differences in binding site interactions not only between 1 and 2, but also between 2 and 2a and between the stereoisomers of 2 accounting for the critical role played, in the case of the pyrrolidinyl-benzodioxanes, by the chirality of both the stereolabile and stereostable stereogenic atoms, namely the protonated tertiary nitrogen and the two asymmetric carbons. (C) 2008 Elsevier Ltd. All rights reserved.