tetraethyl n-butylidene-1,1-bisphosphonate | 107954-87-0

• 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: tetraethyl n-butylidene-1,1-bisphosphonate
• 英文别名: O,O,O,O-tetraethylbutylidenediphosphonate；tetraethyl butylidenebisphosphonate；diethyl butylidenediphosphonate；1,1-Bis(diethoxyphosphoryl)butane
• CAS: 107954-87-0
• 化学式: C₁₂H₂₈O₆P₂
• 分子量: 330.298
• InChiKey: GDVYZALIQPJMRA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  12
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 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 n-butylidene-1,1-bisphosphonate 在 sodium hydride 、 Selectfluor 作用下， 以 四氢呋喃 、 正己烷 、 mineral oil 、 N,N-二甲基甲酰胺 为溶剂， 反应 5.25h， 以47%的产率得到tetraethyl (1-fluorobutane-1,1-diyl)bis(phosphonate)
  参考文献：
  名称：

  1-(Fluoroalkylidene)-1,1-bisphosphonic acids are potent and selective inhibitors of the enzymatic activity of Toxoplasma gondii farnesyl pyrophosphate synthase

  摘要：

  研究人员设计、合成了源自脂肪酸的α-氟化-1,1-二膦酸，并针对南美锥虫病病原体克鲁氏锥虫和弓形虫（弓形虫是弓形虫病的病原体）以及克鲁氏锥虫（TcFPPS）和弓形虫（TgFPPS）的目标寄生酶焦磷酸法尼基合成酶进行了生物评估。有趣的是，1-氟壬亚基-1,1-二膦酸（化合物 43）在低纳摩尔范围内对 TgFPPS 的酶活性具有极强的抑制作用，IC50 为 30 nM。与作为阳性对照的利塞膦酸（IC50 = 74 nM）相比，该化合物的效力高出两倍。这种酶活性对淋病双球菌的细胞生长有很强的抑制作用，IC50 值为 2.7 μM。

  DOI：

  10.1039/c1ob06602a
• 作为产物：
  描述：

  1-丁基膦酸二乙酯 在 盐酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 为溶剂， 反应 0.33h， 生成 tetraethyl n-butylidene-1,1-bisphosphonate
  参考文献：
  名称：

  Alkylidènediphosphonates et vinylphosphonates: une démarche synthétiques sélective par voie carbanionique

  摘要：

  DOI：

  10.1016/0022-328x(86)80147-4

文献信息

• METAL COMPLEX COMPOUND, CANCER THERAPEUTIC COMPOSITION COMPRISING THE METAL COMPLEX COMPOUND AS ACTIVE INGREDIENT, AND INTERMEDIATE FOR PRODUCTION OF THE METAL COMPLEX COMPOUND
  申请人：TMRC Co., Ltd.

  公开号：EP2177525A1

  公开（公告）日：2010-04-21

  A metal complex compound which exhibits a high degree of adsorption to bone or inhibition of cell growth, and is highly effective for therapy of a cancer metastasized to bone and therapy of the primary carcinoma thereof; a therapeutic agent composition for a cancer containing as an active ingredient the metal complex compound or a physiologically acceptable salt thereof; and an intermediate for the metal complex compound are provided. More concretely, a metal complex compound represented by the following General Formula (1): (wherein R1 independently represents C1-C10 alkyl which may be branched or have a substituent; or a C3-C30 cyclic group which may have a substituent; and X represents CHR2, an oxygen atom or NR5); a therapeutic agent composition for a cancer containing it as an active ingredient; and an intermediate for the metal complex compound are provided.

  提供了一种金属配合物化合物，该化合物具有高度吸附到骨骼或抑制细胞生长的特性，对于已经转移到骨骼的癌症和原发癌症的治疗非常有效；一种含有金属配合物化合物或其生理上可接受的盐为活性成分的癌症治疗剂组合物；以及金属配合物的中间体。更具体地，提供了由下述一般式（1）表示的金属配合物化合物：（其中R1独立表示可能是支链或具有取代基的C1-C10烷基；或可能具有取代基的C3-C30环状基团；X表示CHR2、氧原子或NR5）；一种含其为活性成分的癌症治疗剂组合物；以及金属配合物的中间体。
• Michael addition of Grignard reagents to tetraethyl ethenylidenebisphosphonate
  作者：Marco L Lolli、Loretta Lazzarato、Antonella Di Stilo、Roberta Fruttero、Alberto Gasco

  DOI：10.1016/s0022-328x(02)01179-8

  日期：2002.5

  Tetraethyl ethenylidenebisphosphonate can undergo facile Michael type addition reaction with simple Grignard reagents to give alkyl, arylalkyl, aryl C-substituted methylene bisphosphonates. This addition easily occurs even if funtionalised Grignard reagents are used.

  乙撑亚乙基双膦酸酯四乙酯可以与简单的格氏试剂进行容易的迈克尔型加成反应，得到烷基，芳基烷基，芳基C-取代的亚甲基双膦酸酯。即使使用功能化的格氏试剂，这种添加也很容易发生。
• A FACILE APPROACH FOR THE SYNTHESIS OF α -HALOGENATED ALKYLIDENEDIPHOSPHONATES BY REACTION OF ALKYLLITHIUM WITH CHLOROPHOSPHATE AND HALOGEN REAGENT
  作者：Chunbo Lai、Chanjuan Xi、Yuping Feng

  DOI：10.1080/10426500490262621

  日期：2004.3.1

  Alkyllithium reacts with chlorophosphate to generate the α -lithio- alkylidenediphosphonate, which further reacts with halogen reagents to afford corresponding α -halogenated alkylidenediphosphonates.

  烷基锂与氯磷酸盐反应生成 α-硫代亚烷基二膦酸酯，其进一步与卤素试剂反应生成相应的 α-卤代亚烷基二膦酸酯。
• Solid-liquid two-phase alkylation of tetraethyl methylenebisphosphonate under microwave irradiation
  作者：István Greiner、Alajos Grün、Krisztina Ludányi、György Keglevich

  DOI：10.1002/hc.20648

  日期：——

  Optimum conditions for the solid–liquid phase alkylation of tetraethyl methylenebisphosphonate are dependent on the nature of the alkyl halide. The benzylation with benzyl bromide takes place efficiently in boiling acetonitrile in the presence of potassium carbonate and a phase transfer catalyst. The ethylation with ethyl iodide was best accomplished under solventless microwave conditions in the presence

  亚甲基双膦酸四乙酯固液相烷基化的最佳条件取决于卤代烷的性质。在碳酸钾和相转移催化剂存在下，在沸腾的乙腈中用苄基溴有效地进行苄基化。在碳酸铯存在和鎓盐不存在的情况下，在无溶剂微波条件下最好用碘乙烷进行乙基化。由于混合酯的形成，类似的丙基化和丁基化变得复杂。© 2010 Wiley Periodicals, Inc. 杂原子化学 22:11–, 2011; 在 wileyonlinelibrary.com 上在线查看这篇文章。DOI 10.1002/hc.20648
• Bisphosphonates derived from fatty acids are potent inhibitors of Trypanosoma cruzi farnesyl pyrophosphate synthase
  作者：Sergio H. Szajnman、Andrea Montalvetti、Youhong Wang、Roberto Docampo、Juan B. Rodriguez

  DOI：10.1016/s0960-894x(03)00663-2

  日期：2003.10

  Studies on the mode of action of a series of bisphosphonates derived from fatty acids, which had previously proved to be potent inhibitors against Trypanosoma cruzi proliferation in in vitro assays, have been performed. Some of these drugs proved to be potent inhibitors against the intracellular form of the parasite, exhibiting IC50 values at the low micromolar level. As bisphosphonates are FDA clinically approved for treatment of bone resorption disorders, their potential innocuousness makes them good candidates to control tropical diseases. (C) 2003 Elsevier Ltd. All rights reserved.