3-aminopropylphosphinic acid | 103680-47-3

• 分子结构分类: 有机化合物 - 有机磷化合物
• 英文名称: 3-aminopropylphosphinic acid
• 英文别名: CGP 27492；(3-aminopropyl)phosphinic acid；3-aminopropanephosphinic acid；3-amnopropylphosphonous acid；CGP27492；3-APPA
• CAS: 103680-47-3
• 化学式: C₃H₁₀NO₂P
• 分子量: 123.092
• InChiKey: ZTHNRNOOZGJLRR-UHFFFAOYSA-N

物化性质

• 熔点：
  209-213 °C
• 沸点：
  277.8±42.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -4
• 重原子数：
  7
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  63.3
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  2-8°C，干燥

制备方法与用途

3-氨丙基膦酸（3-APPA）是一种GABA的膦酸类似物，能够激活GABAB受体。

反应信息

• 作为反应物：
  描述：

  N-(2,3-环氧丙基)邻苯二甲酰胺 、 3-aminopropylphosphinic acid 在 盐酸 、 N,N-二异丙基乙胺 、 六甲基二硅氮烷 作用下， 生成 (3-aminopropyl)(3-N-phthalimido-2(R,S)-hydroxypropyl)phosphinic acid hydrochloride
  参考文献：
  名称：

  Phosphinic Acid Analogs of GABA. 2. Selective, Orally Active GABAB Antagonists

  摘要：

  In 1987, 25 years after the synthesis of the potent and selective GABA(B) agonist baclofen (1), Kerr et al.(5) described the first GABA(B) antagonist phaclofen 2. However, phaclofen and structurally similar derivatives 3-5 did not cross the blood-brain barrier and hence were inactive in vivo as central nervous system agents. As a consequence, the therapeutic potential of GABA(B) antagonists remained unclear. In exploring GABA and baclofen derivatives by replacing the carboxylic acid residue with various phosphinic acid groups, we discovered more potent and water soluble GABA(B) antagonists. Electrophysiological experiments in vivo demonstrated that some of the new compounds were capable of penetrating the blood-brain barrier after oral administration. Neurotransmitter release experiments showed that they interacted with several presynaptic GABA(B) receptor subtypes, enhancing the release of GABA, glutamate, aspartate, and somatostatin. The new GABA(B) antagonists interacted also with postsynaptic GABA(B) receptors, as they blocked late inhibitory postsynaptic potentials. They facilitated the induction of long-term potentiation in vitro and in, vivo, suggesting potential cognition enhancing effects. Fifteen compounds were investigated in Various memory and learning paradigms in rodents. Although several compounds were found to be active, only 10 reversed the age-related deficits of old rats in a multiple-trial one-way active avoidance test after chronic treatment. The cognition facilitating effects of 10 were confirmed in learning experiments in Rhesus monkeys. The novel GABA(B) antagonists showed also protective effects in various animal models of absence epilepsy.

  DOI：

  10.1021/jm00017a016
• 作为产物：
  描述：

  丙烯胺 在 溶剂黄146 sodium hypophosphite 、 air 、 三乙基硼 作用下， 以 甲醇 、 正己烷 为溶剂， 反应 2.0h， 以42%的产率得到3-aminopropylphosphinic acid
  参考文献：
  名称：

  三乙基硼烷引发的亚磷酸酯在室温下自由基加成到烯烃中：单取代次膦酸和酯的合成。

  摘要：

  描述了从次磷酸盐或酯中单取代的次膦酸（烷基亚膦酸）衍生物的新颖实用方法。以Et（3）B / O（2）引发以磷为中心的自由基形成，并且该反应可在室温下于开放式烧瓶中方便地进行。与先前报道的次磷酸和次磷酸钠的自由基反应条件（过氧化物引发剂，酸催化作用，热）相反，该方法在中性条件下进行，因此可耐受各种官能团。以前无法获得的次膦酸可以一步一步由廉价的原料制备。对于单加成观察到极好的选择性，并且对称的次膦酸二烷基酯没有大量形成。单取代的次膦酸通常通过简单的萃取后处理即可获得高于90％的纯度。但是，如果取代基是极性的，则分离的产率会降低。由于衍生自次磷酸盐的自由基是亲电的，因此该反应仅限于使用富含电子的烯烃。反应条件也可用于室温下烷基卤的自由基还原，并提供了使用氢化三丁基锡的异常温和和环保的替代方法。反应条件的显着温和性质使敏感的次磷酸烷基酯发生自由基反应，在这种情况下，催化量的Et（3）B足以以合理

  DOI：

  10.1021/jo015876i

文献信息

• Substituted propane-phosphinic acid compounds
  申请人：Ciba-Geigy Corporation

  公开号：US05064819A1

  公开（公告）日：1991-11-12

  Compounds of the formula I ##STR1## wherein R denotes an aliphatic, cycloaliphatic, cycloaliphatic-aliphatic or araliphatic radical having 2 or more carbon atoms, and wherein one of the groups R.sup.1, R.sup.2 and R.sup.3 represents hydrogen or an aliphatic, cycloaliphatic, araliphatic or aromatic radical, another one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen or, in the case of R.sup.1 and R.sup.2, is hydroxy, and the remaining one of R.sup.1, R.sup.2 and R.sup.3 is hydrogen, or wherein R denotes methyl, R.sub.1 denotes hydrogen or hydroxy, R.sub.2 denotes an aromatic radical and R.sub.3 represents hydrogen, and their salts have GABA.sub.B -antagonistic properties and can be used as GABA.sub.B -antagonists. They are obtained when in a compound of formula II ##STR2## in which R, R.sup.1, R.sup.2 and R.sup.3 have their previous significances, Z represents --NH.sub.2 and R.sup.4 denotes a hydroxy-protective group R.sup.5 or, when R.sup.1 and R.sup.3 denote hydrogen and R.sup.2 denotes hydrogen or alkyl, denotes an alkali metal or ammonium ion R.sup.6, or Z represents a protected or latent amino group Z.sup.0 and R.sup.4 denotes hydrogen or a hydroxy-protective group R.sup.5, any group R.sup.5 or R.sup.6 is replaced by hydrogen, and/or any group Z.sup.0 is converted into --NH.sub.2.

  公式I的化合物##STR1##其中R表示具有2个或更多碳原子的脂肪族、环脂族、环脂族-脂肪族或芳基脂肪基，其中R.sup.1、R.sup.2和R.sup.3中的一个代表氢或脂肪族、环脂族、芳基脂肪基或芳香族基，R.sup.1、R.sup.2和R.sup.3中的另一个是氢或在R.sup.1和R.sup.2的情况下是羟基，而R.sup.1、R.sup.2和R.sup.3中的剩余一个是氢，或者R表示甲基，R.sub.1表示氢或羟基，R.sub.2表示芳基，R.sub.3表示氢，它们的盐具有GABA.sub.B-拮抗性质，可用作GABA.sub.B-拮抗剂。当在公式II的化合物中获得它们##STR2##其中R、R.sup.1、R.sup.2和R.sup.3具有其先前的含义，Z表示--NH.sub.2，R.sup.4表示羟基保护基R.sup.5或者当R.sup.1和R.sup.3表示氢且R.sup.2表示氢或烷基时，表示碱金属或铵离子R.sup.6，或者Z表示受保护或潜在的氨基Z.sup.0且R.sup.4表示氢或羟基保护基R.sup.5，任何一个R.sup.5或R.sup.6基团被氢取代，和/或任何一个Z.sup.0基团被转化为--NH.sub.2。
• Recent advances in phosphorus–carbon bond formation: synthesis of H-phosphinic acid derivatives from hypophosphorous compounds
  作者：Jean-Luc Montchamp

  DOI：10.1016/j.jorganchem.2004.10.005

  日期：2005.5

  This account summarizes the research conducted in our laboratory over the past five years. New methodologies were devised for the formation of P–C bonds with a focus on the reactions of hypophosphorous acid derivatives. Three types of reactions have been developed: palladium-catalyzed cross-coupling, room-temperature radical addition, and palladium-catalyzed addition. Our results are summarized in

  该报告总结了过去五年来我们实验室进行的研究。设计了新的方法来形成P-C键，重点是次磷酸衍生物的反应。已经开发出三种类型的反应：钯催化的交叉偶联，室温自由基加成和钯催化的加成。我们在所有这些领域中总结了我们的结果，其中包括一些我们的最新数据。（1）我们的钯催化交叉偶联已扩展到烷基次膦酸酯与各种芳基，杂芳基甚至烯基亲电试剂的直接偶联。（2）在自由基条件下添加次磷酸钠从烯烃延伸至炔烃。
• UV-mediated hydrophosphinylation of unactivated alkenes with phosphinates under batch and flow conditions
  作者：Fabien Gelat、Maxime Roger、Christophe Penverne、Ahmed Mazzad、Christian Rolando、Laëtitia Chausset-Boissarie

  DOI：10.1039/c7ra12977g

  日期：——

  hydrophosphinylation of unactivated alkenes with H-phosphinates and hypophosphorous acid under radical free conditions is presented. The reaction affords selectively a large number of structurally diverse organophosphorous compounds in moderate to good yields under mild reaction conditions in the presence of an organic sensitizer as catalyst irradiated by UV-A LEDs. Furthermore, the high yielding hydrophosphinylation

  提出了在自由基条件下用H-次膦酸盐和次磷酸对未活化的烯烃进行 UV 介导的氢膦酰化反应。在有机敏化剂作为催化剂的情况下，在 UV-A LED 照射下，该反应在温和的反应条件下以中等至良好的产率选择性地提供大量结构多样的有机磷化合物。此外，公开了连续流中的高产率氢膦酰化。
• Phosphinic Acid Analogs of GABA. 1. New Potent and Selective GABAB Agonists
  作者：Wolfgang Froestl、Stuart J. Mickel、Roger G. Hall、Georg von Sprecher、Dietrich Strub、Peter A. Baumann、Felix Brugger、Conrad Gentsch、Joachim Jaekel

  DOI：10.1021/jm00017a015

  日期：1995.8

  replacing the carboxylic acid group of GABA or baclofen derivatives with either the phosphinic acid or the methylphosphinic acid residue. Surprisingly, ethyl- and higher alkylphosphinic acid derivatives of GABA yielded novel GABAB antagonists, which are described in part 2 of this series. Structure-activity relationships of the novel GABAB agonists are discussed with respect to their affinities to GABAB

  抗痉挛剂和肌肉松弛剂巴氯芬1是对双小分子不敏感的GABA B受体的有效选择性激动剂。多年来，获得出色的GABA B激动剂的努力一直没有成功。我们描述了两个新系列的GABA B激动剂的合成和生物学特性，在体外和体内，最好的化合物比巴氯芬更有效。它们是通过用次膦酸或甲基次膦酸残基取代GABA或巴氯芬衍生物的羧酸基团而获得的。出人意料的是，GABA的乙基和高级烷基次膦酸衍生物产生了新型GABAB拮抗剂，在本系列的第2部分中对此进行了描述。
• Convenient syntheses of phosphinic analogues of γ-aminobutyric- and glutamic acids
  作者：M. A. Khomutov、A. A. Formanovsky、I. V. Mikhura、J. Vepsalainen、S. N. Kochetkov、D. De Biase、A. R. Khomutov

  DOI：10.1134/s1068162016060042

  日期：2016.11

  of 66%. 3-Aminopropylphosphinic acid was prepared from allylamine in three steps with an overall yield of 56%. These improved protocols allowed to obtain these commercially unavailable phosphinic analogues of glutamic acid and GABA for testing on potential molecular targets.

  由乙烯基次膦酸二丁酯三步一锅法合成2-氨基-4-(羟基次膦基)丁酸，总收率为66%。以烯丙胺为原料，分三步制备3-氨基丙基次膦酸，总收率为56%。这些改进的方案允许获得这些商业上无法获得的谷氨酸和 GABA 的次膦酸类似物，用于测试潜在的分子靶标。