tetraethyl (but-3-yne-1,1-diyl)bisphosphonate | 154384-16-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: tetraethyl (but-3-yne-1,1-diyl)bisphosphonate
• 英文别名: tetraethyl but-3-yne-1,1-diyldiphosphonate；tetraethyl (3-butyn-1-ylidene)-1,1-bisphosphonate；4,4-bis(diethoxyphosphoryl)but-1-yne
• CAS: 154384-16-4
• 化学式: C₁₂H₂₄O₆P₂
• 分子量: 326.266
• InChiKey: SOYFRPJGNFZJEP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  20
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  tetraethyl (but-3-yne-1,1-diyl)bisphosphonate 在 双氧水 、 sodium hexamethyldisilazane 作用下， 以 四氢呋喃 、 苯 为溶剂， 反应 1.5h， 生成 3-butyn-1-ylidynetrisphosphonic acid hexaethyl ester
  参考文献：
  名称：

  Synthesis and Reactivity of Alkyl-1,1,1-trisphosphonate Esters

  摘要：

  The alpha-trisphosphonic acid esters provide a unique spatial arrangement of three phosphonate groups and may represent an attractive motif for inhibitors of enzymes that utilize di- or triphosphate substrates To advance studies of this unique functionality, a general route to alkyl derivatives of the parent system (R = H) has been developed. A set of new alpha-alkyl-1,1,1-trisphosphonate esters has been prepared through phosphinylation and subsequent oxidation of tetraethyl alkylbisphosphonates, and the reactivity of these new compounds has been studied in representative reactions that afford additional examples of this functionality.

  DOI：

  10.1021/jo201523w
• 作为产物：
  描述：

  tetraethyl (2-methoxyethane-1,1-diyl)bis(phosphonate) 在 对甲苯磺酸 作用下， 以 四氢呋喃 、 5,5-dimethyl-1,3-cyclohexadiene 、 甲苯 为溶剂， 反应 19.0h， 生成 tetraethyl (but-3-yne-1,1-diyl)bisphosphonate
  参考文献：
  名称：

  通过正交点击反应的荧光标记辅助合成胆汁酸-双膦酸酯共轭物：获得潜在的抗吸收性骨药物的途径

  摘要：

  据报道，合成了少量新的胆汁酸-双膦酸盐（BA-BP）偶联物作为潜在的候选药物。所披露的方法分别依赖于BA支架的头尾位置上的叠氮化物和硫醇官能团的安装以及随后通过正交点击反应（铜催化的叠氮化物-炔环加成，硫醇-烯或硫醇-炔偶联）的修饰）引入BP单元和荧光团。由于通过标准程序难以分离靶标结合物，因此该方法最终以具有轻质荧光标签的BA支架功能化，从而通过荧光固相萃取快速有效地纯化中间体和最终产物。

  DOI：

  10.1039/c7ob00774d

文献信息

• Synthesis of functionalized bisphosphonates via click chemistry
  作者：Hanna Skarpos、Sergey N. Osipov、Daria V. Vorob'eva、Irina L. Odinets、Enno Lork、Gerd-Volker Röschenthaler

  DOI：10.1039/b705510b

  日期：——

  An efficient general synthetic approach giving the possibility for facile, rapid and cheap access to a wide range of novel nitrogen-bisphosphonates (N-BPs) as potent drug candidates, based on the reaction of mono- and bis-propargyl-substituted bisphosphonates with a variety of azides under Cu(I) catalysis (“click” methodology), has been developed. The method allows the incorporation of two functionalities into the N-BP molecule simultaneously, as well as to ligate in situ two N-BPs to one another via the one-pot reaction of organic dibromides with propargyl-substituted bisphosphonates, generating both the diazide and Cu(I) moieties.

  一种高效的综合合成方法已经被开发出来，使得可以轻松、快速且廉价地获得大量新型的氮二膦酸盐（N-BPs）作为强效药物候选物。这种方法基于单取代和双取代的炔丙基二膦酸盐与多种叠氮化物在铜(I)催化下的反应（即“点击化学”方法）。该方法能够同时将两种功能性基团引入N-BP分子，并且可以通过一步反应将有机二溴化物与炔丙基取代的二膦酸盐连接起来，同时在原位生成二叠氮基团和铜(I)单元，从而实现两个N-BP分子之间的交联。
• [EN] FLUORESCENT BISPHOSPHONATE ANALOGS<br/>[FR] ANALOGUES DE BISPHOSPHONATES FLUORESCENTS
  申请人：UNIV SOUTHERN CALIFORNIA

  公开号：WO2016161407A1

  公开（公告）日：2016-10-06

  Fluorescent probes based on N-heterocyclic bisphosphonates or their phosphonocarboxylate analogues are provided. The probes have variable spectroscopic properties, bone mineral binding affinities, and pharmacological activities. Methods for preparing the probes include the use of two complementary linking strategies, one involving an amino group and the other involving a chloride group as a precursor to an amino group. In other versions, bifunctional N-heterocyclic bisphosphonates are provided having an amino group and an azido group as linking moieties. In some versions, the linking chemistry allows attachment of a wide selection of fluorescent dyes in the visible to near-infrared range to any of three clinically important heterocyclic bisphosphonates.

  基于N-杂环双膦酸盐或其膦酸盐类似物的荧光探针已提供。这些探针具有可变的光谱特性、骨矿物结合亲和力和药理活性。制备这些探针的方法包括使用两种互补的连接策略，一种涉及氨基团，另一种涉及氯化物作为氨基团的前体。在其他版本中，提供了具有氨基团和偶氮基团作为连接基团的双功能N-杂环双膦酸盐。在某些版本中，连接化学允许将广泛选择的荧光染料附着在可见光到近红外范围内的三种临床重要的杂环双膦酸盐中的任何一种上。
• Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity
  作者：Oleg I. Artyushin、Elena V. Sharova、Natalya M. Vinogradova、Galina K. Genkina、Aleksandra A. Moiseeva、Zinaida S. Klemenkova、Iana R. Orshanskaya、Anna A. Shtro、Renata A. Kadyrova、Vladimir V. Zarubaev、Olga I. Yarovaya、Nariman F. Salakhutdinov、Valery K. Brel

  DOI：10.1016/j.bmcl.2017.03.051

  日期：2017.5

  A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess

  用点击化学方法合成了一系列的十七种1,7,7-三甲基-[2.2.1]双环庚烷四唑衍生物，并用光谱数据进行了表征。对获得的化合物的MDCK细胞中的针对流感病毒A / Puerto Rico / 8/34（H1N1）的细胞毒性和体外抗病毒活性进行了研究。结构-活性关系分析表明，该组化合物具有病毒抑制活性，应带有带有短连接基（C2-C4）的氧原子，为羟基（18、19、29），酮基（21）或作为杂环（24）的一部分。这些化合物显示出低细胞毒性以及高抗病毒活性。
• Stereocontrolled regeneration of olefins from epoxides
  作者：Veronica S. Wills、Xiang Zhou、Cheryl Allen、Sarah A. Holstein、David F. Wiemer

  DOI：10.1016/j.tetlet.2016.02.041

  日期：2016.3

  epoxides can be converted to olefins. This reaction now has been shown to tolerate remote olefins without loss of their individual stereochemistry. A reaction sequence involving regiospecific epoxidation of an isoprenoid alcohol, conversion of the alcohol to an azide, and cycloaddition with an acetylene, followed by conversion of the epoxide back to the original olefin, has allowed stereocontrolled

  通过用NaI和大概在原位形成三氟乙酰碘的三氟乙酸酐处理，可以将环氧化物转化为烯烃。现在已经表明该反应可以耐受偏远的烯烃，而不会损失其单独的立体化学。涉及异戊二烯醇的区域特异性环氧化，将醇转化为叠氮化物，并与乙炔进行环加成，然后将环氧化物转化回原始烯烃的反应序列，可以立体控制制备具有法呢基或香叶基香叶基的三唑双膦酸酯。取代基。该策略可以适用于选择性保护其他聚烯烃中的烯烃，包括用于复分解反应的底物。
• 3,5-Bis(Arylidene)-4-Piperidones Modified by Bisphosphonate Groups as Novel Anticancer Agents
  作者：Mikhail V. Makarov、Ekaterina Yu. Rybalkina、Valery K. Brel

  DOI：10.1080/10426507.2014.976338

  日期：2015.6.3

  GRAPHICAL ABSTRACT Abstract Synthetic approaches for conjugating 3,5-bis(arylidene)-4-piperidones with bisphosphonate moiety were elaborated. These approaches are based either on reaction of Grignard reagent containing dioxolane protected 4-piperidone with tetraethyl ethylidenbisphosphonate followed by crotonic condensation with aromatic aldehydes or on Cu(i) catalyzed 1,3-cycloaddition of tetraethyl

  图形摘要 摘要 详细阐述了将 3,5-双（亚芳基）-4-哌啶酮与双膦酸酯部分结合的合成方法。这些方法基于含有二氧戊环保护的 4-哌啶酮的格氏试剂与亚乙基双膦酸四乙酯的反应，然后与芳香醛的巴豆缩合，或基于 Cu(i) 催化的四乙基丁-3-炔-1,1-的 1,3-环加成反应二基双膦酸酯转化为 N-(2-叠氮乙基)-3,5-双(亚芳基)-4-哌啶酮，生成相应的 1,2,3-三唑衍生物。合成的缀合物的细胞毒活性取决于连接哌啶酮氮原子和双膦酸酯残基的接头的长度。3的三唑衍生物，