but-3-en-1-yl phosphonic acid | 209598-67-4

• 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: but-3-en-1-yl phosphonic acid
• 英文别名: But-3-en-1-ylphosphonic acid；but-3-enylphosphonic acid
• CAS: 209598-67-4
• 化学式: C₄H₉O₃P
• 分子量: 136.087
• InChiKey: KJLQJEWLKADPDQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  8
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  57.5
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  but-3-en-1-yl phosphonic acid 在 草酰氯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 but-3-en-1-ylphosphonic dichloride
  参考文献：
  名称：

  膦酸酯模板上的闭环易位反应

  摘要：

  描述了在由亚烷基钌3催化的膦酸酯模板上的闭环易位反应的第一实例。这些反应中的产率，速率和环化方式对简单的烯烃取代很敏感。该方法的亮点是2-烷氧基-3,6-二氢-[1,2]氧杂膦-2-氧化物杂环的有效合成（2）。

  DOI：

  10.1016/s0040-4039(98)00728-x
• 作为产物：
  描述：

  3-丁烯基磷羧酸乙酯 在 三甲基溴硅烷 作用下， 以 二氯甲烷 为溶剂， 反应 2.33h， 生成 but-3-en-1-yl phosphonic acid
  参考文献：
  名称：

  磷霉素的基于氨基酸的前药替代了抗疟药和抗结核药。

  摘要：

  磷霉素是一种天然抗生素，具有有希望的IspC（DXR，1-脱氧-d-木酮糖-5-磷酸还原异构酶）抑制活性。该酶催化非甲羟戊酸类异戊二烯生物合成途径的第一步，这在恶性疟原虫和结核分枝杆菌中是必不可少的。磷霉素主要由于其高极性而显示出次佳的药代动力学性质。此外，由于磷霉素不能穿透细菌细胞壁，因此它对结核分枝杆菌无活性。暂时掩盖膦酸酯部分作为前药具有解决这两个问题的潜力。我们报道了基于两种氨基酸的前药方法在一种磷霉素替代品上的应用。膦酸酯部分向酪氨酸衍生的酯的转化增加了针对恶性疟原虫无性血液阶段的体外活性，而膦酰二氨基甲酸酯类前药显示出有希望的抗结核活性。在伯氏疟疾疟疾小鼠模型中体内测试了选定的前药。这些结果表明良好的体内抗疟原虫潜力。

  DOI：

  10.1016/j.bmc.2019.01.016

文献信息

• [EN] PHOSPHOANTIGEN PRODRUG COMPOUNDS<br/>[FR] COMPOSÉS DE TYPE PROMÉDICAMENT PHOSPHOANTIGÈNE
  申请人：UNIV COLLEGE CARDIFF CONSULTANTS LTD

  公开号：WO2020008189A1

  公开（公告）日：2020-01-09

  The invention relates to a compound of General Formula (I): wherein R1, R2, R3, R4 and R5 are as defined herein. Compounds and compositions comprising the same exhibit high serum stability and potent activation of the γδ T-cell immune response, so are suitable for use in immunotherapy. The invention also relates to methods of immunotherapy using the compounds of General Formula (I).

  该发明涉及一种一般式（I）的化合物：其中R1、R2、R3、R4和R5如本文所定义。包含该化合物的化合物和组合物表现出高血清稳定性和强大的γδ T细胞免疫应答激活，因此适用于免疫疗法。该发明还涉及使用一般式（I）化合物的免疫疗法方法。
• Remote Supramolecular Control of Catalyst Selectivity in the Hydroformylation of Alkenes
  作者：Paweł Dydio、Wojciech I. Dzik、Martin Lutz、Bas de Bruin、Joost N. H. Reek

  DOI：10.1002/anie.201005173

  日期：2011.1.10

  In the pocket: The supramolecular interactions between a Rh phosphine catalyst equipped with an anion‐binding pocket and alkenes that contain anionic functionalities (see picture) provide an excellent design concept to achieve remote control of the regioselectivity in hydroformylation reactions. The 4‐pentenoate and 3‐butenylphosphonate, which fit tightly between the Rh center and the pocket, were

  囊中之物：配备有阴离子结合囊的Rh膦催化剂与包含阴离子官能团的烯烃之间的超分子相互作用（参见图片）提供了出色的设计理念，可远程控制加氢甲酰化反应中的区域选择性。紧密位于Rh中心和口袋之间的4-戊烯酸酯和3-丁烯基膦酸酯以前所未有的选择性加氢甲酰化。
• Phosphonodiamidate prodrugs of N-alkoxy analogs of a fosmidomycin surrogate as antimalarial and antitubercular agents
  作者：Charlotte Courtens、Martijn Risseeuw、Guy Caljon、Paul Cos、Anandi Martin、Serge Van Calenbergh

  DOI：10.1016/j.bmcl.2019.03.008

  日期：2019.5

  A series of N-alkoxy analogs of a l-leucine ethyl ester phosphonodiamidate prodrug of a fosmidomycin surrogate were synthesized and investigated for their ability to inhibit in vitro growth of P. falciparum and M. tuberculosis. These compounds originate by merging a previously reported successful phosphonate derivatisation with favorable modifications of the hydroxamate moiety. None of the synthesized

  合成了磷霉素替代物的1-亮氨酸乙酯磷酸膦二酰胺酯前药的一系列N-烷氧基类似物，并研究了它们抑制恶性疟原虫和结核分枝杆菌生长的能力。这些化合物通过合并先前报道的成功的膦酸酯衍生化与异羟肟酸酯部分的有利修饰而产生。与母体游离异羟肟酸酯类似物相比，合成的化合物均未显示出对恶性疟原虫或结核分枝杆菌的增强活性。
• Steric Control over the Threading of Pyrophosphonates with One or Two Cyanostar Macrocycles during Pseudorotaxane Formation
  作者：Julian Vogel、Yusheng Chen、Rachel E. Fadler、Amar H. Flood、Max von Delius

  DOI：10.1002/chem.202300899

  日期：2023.7.20

  The supramolecular recognition of anions is increasingly harnessed to achieve the self‐assembly of supramolecular architectures, ranging from cages and polymers to (pseudo)rotaxanes. The cyanostar (CS) macrocycle has previously been shown to form 2 : 1 complexes with organophosphate anions that can be turned into [3]rotaxanes by stoppering. Here we achieved steric control over the assembly of pseudorotaxanes comprising the cyanostar macrocycle and a thread that is based, for the first time, on organo‐pyrophosphonates. Subtle differences in steric bulk on the threads allowed formation of either [3]pseudorotaxanes or [2]pseudorotaxanes. We demonstrate that the threading kinetics are governed by the steric demand of the organo‐pyrophosphonates and in one case, slows down to the timescale of minutes. Calculations show that the dianions are sterically offset inside the macrocycles. Our findings broaden the scope of cyanostar‐anion assemblies and may have relevance for the design of molecular machines whose directionality is a result of relatively slow slipping.

  摘要阴离子的超分子识别越来越多地被用于实现超分子结构的自组装，从笼状结构、聚合物到（伪）轮烷。此前已有研究表明，氰星（CS）大环与有机磷酸酯形成 2 ：1 的复合物，这些复合物可以通过堵塞变成 [3]rotaxanes 。在这里，我们首次实现了对由蓝星大环和基于有机-焦磷酸盐的线组成的假轮烷组装的立体控制。螺纹上立体体积的细微差别使得[3]赝轴烷或[2]赝轴烷得以形成。我们证明，穿线动力学受有机-焦磷酸盐的立体需求支配，在一种情况下，穿线速度会减慢到几分钟。计算结果表明，二离子在大环内部发生了立体偏移。我们的发现拓宽了青柱-阴离子组装的范围，并可能对设计其方向性是相对缓慢滑动结果的分子机器有意义。
• Aryloxy Diester Phosphonamidate Prodrugs of Phosphoantigens (ProPAgens) as Potent Activators of Vγ9/Vδ2 T-Cell Immune Responses
  作者：Hachemi Kadri、Taher E. Taher、Qin Xu、Maria Sharif、Elizabeth Ashby、Richard T. Bryan、Benjamin E. Willcox、Youcef Mehellou

  DOI：10.1021/acs.jmedchem.0c01232

  日期：2020.10.8

  V gamma 9/V delta 2 T-cells are activated by pyrophosphate-containing small molecules known as phosphoantigens (PAgs). The presence of the pyrophosphate group in these PAgs has limited their drug-like properties because of its instability and polar nature. In this work, we report a novel and short Grubbs olefin metathesismediated synthesis of methylene and difluoromethylene monophosphonate derivatives of the PAg (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBP) as well as their aryloxy diester phosphonamidate prodrugs, termed ProPAgens. These prodrugs showed excellent stability in human serum (t(1/2) > 12 h) and potent activation of V gamma 9/V delta 2 T-cells (EC50 ranging from 5 fM to 73 nM), which translated into sub-nanomolar gamma delta T-cell-mediated eradication of bladder cancer cells in vitro. Additionally, a combination of in silico and in vitro enzymatic assays demonstrated the metabolism of these phosphonamidates to release the unmasked PAg monophosphonate species. Collectively, this work establishes HMBP monophosphonate ProPAgens as ideal candidates for further investigation as novel cancer immunotherapeutic agents.