(2S)-(-)-phenylmethyl 2-(1,2-dihydroxyethyl)pyrrolidine-1-carboxylate | 623938-26-1

• 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: (2S)-(-)-phenylmethyl 2-(1,2-dihydroxyethyl)pyrrolidine-1-carboxylate
• 英文别名: (2S)-N-benzyloxycarbonyl-2-(1,2-dihydroxyethyl)pyrrolidine
• CAS: 623938-26-1
• 化学式: C₁₄H₁₉NO₄
• 分子量: 265.309
• InChiKey: ZTILVFSKVNXIEX-UEWDXFNNSA-N

物化性质

• 沸点：
  457.1±25.0 °C(Predicted)
• 密度：
  1.271±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.14
• 重原子数：
  19.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  70.0
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (2S)-(-)-phenylmethyl 2-(1,2-dihydroxyethyl)pyrrolidine-1-carboxylate 在 lithium aluminium tetrahydride 、 sodium hydride 、 三乙胺 、 偶氮二甲酸二乙酯 、 三甲基膦 作用下， 以 四氢呋喃 、 乙二醇二甲醚 为溶剂， 反应 24.25h， 生成 (S,R)-3-(N-methyl-2-pyrrolidinyl)-2,3-dihydro-1,4-dioxino[2,3-b]pyridine
  参考文献：
  名称：

  From pyrrolidinyl-benzodioxane to pyrrolidinyl-pyridodioxanes, or from unselective antagonism to selective partial agonism at α4β2 nicotinic acetylcholine receptor

  摘要：

  Each of the four aromatic -CH= of (S,R)-2-pyrrolidinyl-1,4-benzodioxane [(S,R)-6] and of its epimer at the dioxane stereocenter (S,S)-6, previously reported as alpha 4 beta 2 nAChR ligands, was replaced with nitrogen. The resulting four diastereoisomeric pairs of pyrrolidinyl-pyridodioxanes were studied for the nicotinic affinity and activity at alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes and compared to their common carbaisostere. It turned out that such isosteric substitutions are highly detrimental, but with the important exception of the S,R stereoisomer of the pyrrolidinyl-pyridodioxane with the pyridine nitrogen adjacent to the dioxane and seven atoms distant from the pyrrolidine nitrogen. Indeed, this stereo/regioisomer not only maintained the alpha 4 beta 2 affinity of [(S,R)-6], but also greatly improved in selectivity over the alpha 3 beta 4 and alpha 7 subtypes and, most importantly, exhibited a highly selective alpha 4 beta 2 partial agonism. The finding that [(S,R)-6] is, instead, an unselective alpha 4 beta 2 antagonist indicates that the benzodioxane substructure confers affinity for the alpha 4 beta 2 nAChR binding site, but activation of this receptor subtype needs benzodioxane functionalization under strict steric requirements, such as the previously reported 7-OH substitution or the present isosteric modification. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.10.048
• 作为产物：
  描述：

  在 sodium tetrahydroborate 、 sodium methylate 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 4.0h， 以97%的产率得到(2S)-(-)-phenylmethyl 2-(1,2-dihydroxyethyl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  From pyrrolidinyl-benzodioxane to pyrrolidinyl-pyridodioxanes, or from unselective antagonism to selective partial agonism at α4β2 nicotinic acetylcholine receptor

  摘要：

  Each of the four aromatic -CH= of (S,R)-2-pyrrolidinyl-1,4-benzodioxane [(S,R)-6] and of its epimer at the dioxane stereocenter (S,S)-6, previously reported as alpha 4 beta 2 nAChR ligands, was replaced with nitrogen. The resulting four diastereoisomeric pairs of pyrrolidinyl-pyridodioxanes were studied for the nicotinic affinity and activity at alpha 4 beta 2, alpha 3 beta 4 and alpha 7 nAChR subtypes and compared to their common carbaisostere. It turned out that such isosteric substitutions are highly detrimental, but with the important exception of the S,R stereoisomer of the pyrrolidinyl-pyridodioxane with the pyridine nitrogen adjacent to the dioxane and seven atoms distant from the pyrrolidine nitrogen. Indeed, this stereo/regioisomer not only maintained the alpha 4 beta 2 affinity of [(S,R)-6], but also greatly improved in selectivity over the alpha 3 beta 4 and alpha 7 subtypes and, most importantly, exhibited a highly selective alpha 4 beta 2 partial agonism. The finding that [(S,R)-6] is, instead, an unselective alpha 4 beta 2 antagonist indicates that the benzodioxane substructure confers affinity for the alpha 4 beta 2 nAChR binding site, but activation of this receptor subtype needs benzodioxane functionalization under strict steric requirements, such as the previously reported 7-OH substitution or the present isosteric modification. (C) 2016 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2016.10.048

文献信息

• α−ヒドロキシカルボン酸の製造方法
  申请人：国立大学法人名古屋大学

  公开号：JP2016008183A

  公开（公告）日：2016-01-18

  【課題】α−ヒドロキシカルボン酸を穏和な条件で効率よく製造する方法、及び前記α−ヒドロキシカルボン酸を含有する原料から生分解性プラスチックを製造する方法の提供。【解決手段】式（１）で表される骨格を含むニトロキシラジカル、水、及び、有機溶剤を用いた反応系において、１，２−ジオール化合物を酸化させてα−ヒドロキシカルボン酸を製造する製造方法であって、上記有機溶剤は、水と混和しない化合物であるα−ヒドロキシカルボン酸の合成方法。（Ｒ１〜Ｒ４は各々独立に、Ｃ１〜６の炭化水素基）上記反応系がｐＨ１．０〜８．０であり、リン酸緩衝液又は酢酸緩衝液を含み、次亜ハロゲン酸塩及び亜ハロゲン酸塩から選ばれた少なくとも１種が添加され、更にテトラアルキルアンモニウム塩及び脂肪酸から選ばれた１種が添加されているα−ヒドロキシカルボン酸の合成方法。【選択図】なし

  在温和条件下高效制备α-羟基羧酸的方法，以及从含有α-羟基羧酸的原料制造生物降解塑料的方法。采用含有式（1）所示骨架的亚硝基自由基、水和有机溶剂的反应体系，氧化1,2-二醇化合物以制备α-羟基羧酸的制备方法，其中所述有机溶剂是与水不混合的化合物，用于合成α-羟基羧酸。（R1-R4各自独立地表示C1-6的烃基）所述反应体系的pH为1.0-8.0，包含磷酸缓冲液或醋酸缓冲液，并添加了选择自次卤酸盐和亚卤酸盐中至少一种的α-羟基羧酸的合成方法，另外还添加了选择自四烷基铵盐和脂肪酸中至少一种的α-羟基羧酸的合成方法。【选择图】无
• Chemoselective Catalytic Oxidation of 1,2-Diols to α-Hydroxy Acids Controlled by TEMPO–ClO₂ Charge-Transfer Complex
  作者：Keisuke Furukawa、Masatoshi Shibuya、Yoshihiko Yamamoto

  DOI：10.1021/acs.orglett.5b01003

  日期：2015.5.1

  Chemoselective catalytic oxidation from 1,2-diols to a-hydroxy acids in a cat. TEMPO/cat. NaOCl/NaClO2 system has been achieved. The use of a two-phase condition consisting of hydrophobic toluene and water suppresses the concomitant oxidative cleavage. A study of the mechanism suggests that the observed selectivity is derived from the precise solubility: control of diols and hydroxy acids as well as the active species Of TEMPO, Although the oxoammonium species TEMPO+Cl- is hydrophilic, the active species dissolves into the organic layer by the formation of the charge-transfer (CT) complex TEMPO-ClO2 under the reaction conditions.
• 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
  作者：Silvia Dei、Cristina Bellucci、Michela Buccioni、Marta Ferraroni、Fulvio Gualtieri、Luca Guandalini、Dina Manetti、Rosanna Matucci、Maria Novella Romanelli、Serena Scapecchi、Elisabetta Teodori

  DOI：10.1016/s0968-0896(03)00236-0

  日期：2003.7

  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.