4-(diethoxyphosphinyl)-3-butyn-1-ol | 7585-82-2

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: 4-(diethoxyphosphinyl)-3-butyn-1-ol
• 英文别名: diethyl (4-hydroxybut-1-yn-1-yl)phosphonate；4-diethoxyphosphorylbut-3-yn-1-ol
• CAS: 7585-82-2
• 化学式: C₈H₁₅O₄P
• 分子量: 206.178
• InChiKey: GZPVGCLKMQTHON-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  13
• 可旋转键数：
  5
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-(diethoxyphosphinyl)-3-butyn-1-ol 在 Pd-BaSO₄ 吡啶 、 4-二甲氨基吡啶 、 氢气 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 25.0 ℃ 、344.73 kPa 条件下， 反应 36.0h， 生成 甘氨酸,N-[4-(二乙氧基氧膦基)-3-丁烯基]-,甲基酯,(Z)-
  参考文献：
  名称：

  Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists

  摘要：

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1

  DOI：

  10.1021/jm00086a005
• 作为产物：
  描述：

  [4-[(Tetrahydro-2H-pyran2-yl)oxy]-1-butynyl]-phosphonic acid, diethyl ester 在 对甲苯磺酸 作用下， 以 甲醇 为溶剂， 生成 4-(diethoxyphosphinyl)-3-butyn-1-ol
  参考文献：
  名称：

  Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists

  摘要：

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1

  DOI：

  10.1021/jm00086a005

文献信息

• Base-Free Direct Synthesis of Alkynylphosphonates from Alkynes and <i>H</i>-Phosphonates Catalyzed by Cu₂O
  作者：Yanina Moglie、Evangelina Mascaró、Victoria Gutierrez、Francisco Alonso、Gabriel Radivoy

  DOI：10.1021/acs.joc.5b02528

  日期：2016.3.4

  A simple and mild methodology for the direct synthesis of alkynylphosphonates is presented. The reaction of a variety of terminal alkynes with dialkyl phosphites in the presence Cu2O (14 mol %) led to the formation of the corresponding alkynylphosphonates in good to excellent yields. Reactions are performed under air, in acetonitrile as solvent, and in the absence of base or ligand additives. This

  提出了一种简单温和的直接合成炔基膦酸酯的方法。在Cu 2 O（14 mol％）存在下，各种末端炔烃与亚磷酸二烷基酯的反应导致形成相应的炔基膦酸酯，产率高至优异。反应在空气中，在乙腈作为溶剂中，在没有碱或配体添加剂的情况下进行。这种新方法与起始炔烃上各种官能团的存在兼容，并且可以放大至克级。
• US5179085A
  申请人：——

  公开号：US5179085A

  公开（公告）日：1993-01-12
• Exploration of N-phosphonoalkyl-, N-phosphonoalkenyl-, and N-(phosphonoalkyl)phenyl-spaced .alpha.-amino acids as competitive N-methyl-D-aspartic acid antagonists
  作者：Christopher F. Bigge、Graham Johnson、Daniel F. Ortwine、James T. Drummond、Daniel M. Retz、Laura J. Brahce、Linda L. Coughenour、Frank W. Marcoux、Albert W. Probert

  DOI：10.1021/jm00086a005

  日期：1992.4

  A series of N-substituted alpha-amino acids containing terminal phosphonic acid groups has been synthesized as potential N-methyl-D-aspartate (NMDA) receptor antagonists. NMDA receptor affinity was determined by displacement of a known ligand ([H-3]CPP) from crude rat brain synaptic membranes; an antagonist action was demonstrated by the inhibition of glutamate-induced accumulation of [Ca-45(2+)] in cultured rat cortical neurons. Receptor affinity was significantly correlated with antagonist activity (Figure 1). Moderate affinity (IC50 = 1-2-mu-M) was retained for analogues (31 and 32, Table 1; and 59 and 66, Table II) with reduced flexibility in their phosphonate side chains and is consistent with entropy playing a role in determining receptor affinity. Modeling studies suggest a folded conformation that brings the distal phosphonic acid group into close proximity with the alpha-carboxylate is required for binding. Each of the active analogues possess entropy-limiting features (double bonds, phenyl rings) in their side chains that allows the superposition of their key NH2, alpha-COOH, and distal PO3H2 groups with those of known competitive antagonists. Affinity decreased for analogues with alpha-carbon substitution, presumably because the alpha-substituent inhibits the folding of these structures into a bioactive conformation and occupies receptor-excluded volume. A complete description of the NMDA antagonist pharmacophore model is provided in a companion paper. 1