5-iodo-1,1-difluoro-1-(diethylphosphono)pentane | 130434-89-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: 5-iodo-1,1-difluoro-1-(diethylphosphono)pentane
• 英文别名: diethyl 1,1-difluoro-5-iodopentylphosphonate；1-Diethoxyphosphoryl-1,1-difluoro-5-iodopentane
• CAS: 130434-89-8
• 化学式: C₉H₁₈F₂IO₃P
• 分子量: 370.115
• InChiKey: LXGLJAFUSVOAHN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  16
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-iodo-1,1-difluoro-1-(diethylphosphono)pentane 在 盐酸 、 三甲基溴硅烷 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 84.0h， 生成 9-(5,5-difluoro-5-phosphonopentyl)guanine hydrochloride
  参考文献：
  名称：

  Halazy; Ehrhard; Danzin, Journal of the American Chemical Society, 1991, vol. 113, # 1, p. 315 - 317

  摘要：

  DOI：
• 作为产物：
  描述：

  1,4-二碘代丁烷 、 二氟甲基膦酸二乙酯 在 六甲基磷酰三胺 、 lithium diisopropyl amide 、 磷酸 、 水 作用下， 以 四氢呋喃 、 乙醚 为溶剂， 反应 7.0h， 以17%的产率得到5-iodo-1,1-difluoro-1-(diethylphosphono)pentane
  参考文献：
  名称：

  Virtual screening, selection and development of a benzindolone structural scaffold for inhibition of lumazine synthase

  摘要：

  Virtual screening of a library of commercially available compounds versus the structure of Mycobacterium tuberculosis lumazine synthase identified 2-(2-oxo-1,2-dihydrobenzo[cd]indole-6-sulfonamido)acetic acid ( 9) as a possible lead compound. Compound 9 proved to be an effective inhibitor of M. tuberculosis lumazine synthase with a K-i of 70 mu M. Lead optimization through replacement of the carboxymethylsulfonamide sidechain with sulfonamides substituted with alkyl phosphates led to a four-carbon phosphate 38 that displayed a moderate increase in enzyme inhibitory activity (K-i 38 mu M). Molecular modeling based on known lumazine synthase/inhibitor crystal structures suggests that the main forces stabilizing the present benzindolone/enzyme complexes involve pi-pi stacking interactions with Trp27 and hydrogen bonding of the phosphates with Arg128, the backbone nitrogens of Gly85 and Gln86, and the side chain hydroxyl of Thr87. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.03.072

文献信息

• Design, Synthesis, and Evaluation of 9-<scp>d</scp>-Ribitylamino-1,3,7,9-tetrahydro-2,6,8-purinetriones Bearing Alkyl Phosphate and α,α-Difluorophosphonate Substituents as Inhibitors of Riboflavin Synthase and Lumazine Synthase
  作者：Mark Cushman、Thota Sambaiah、Guangyi Jin、Boris Illarionov、Markus Fischer、Adelbert Bacher

  DOI：10.1021/jo030278k

  日期：2004.2.1

  consistent with the observed increase in Km of the 3,4-dihydroxybutanone-4-phosphate substrate from 5.2 μM in Tris buffer or from 6.7 μM in MOPS buffer to 50 μM in phosphate buffer when tested on Bacillus subtilis lumazine synthase. However, when tested in Tris buffer vs Mycobacterium tuberculosis lumazine synthase, three of the phosphate inhibitors displayed inhibition constants in the 4−5 nM range

  Lumazine合酶和核黄素合酶催化核黄素的生物合成中的最后两个步骤，核黄素是电子传输过程中必需的代谢产物。为了获得这两种酶的结构探针，以及作为抗生素具有潜在价值的抑制剂，合成了一系列带有烷基磷酸酯和α，α-二氟膦酸酯取代基的核嘌呤嘌呤三酮。由于嘌呤三酮环系统和核糖基羟基可被烷基化，因此在进行所需的烷基化反应之前，合成需要以保护形式生成这两个部分。这些物质被设计为会与其磷酸结合位点结合的鲁那嗪合酶的中间类似物抑制剂。发现所有化合物都是这两种化合物的有效抑制剂。枯草芽孢杆菌lumazine合酶以及大肠杆菌核黄素合酶。3-（1,3,7,9-四氢-9- d -ribityl-2,6,8-三氧嘌呤-7-基）丙烷1-磷酸结合的分子模型为这些化合物的结构提供了结构解释能够有效抑制两种酶。有趣的是，与母体嘌呤三酮相比，这些新化合物的酶动力学出乎意料地证明了磷酸酯和膦酸酯取代基对结合起了负面作用。这些对l
• Synthesis and biological evaluation of 9-(5′,5′-difluoro-5′-phosphonopentyl)guanine derivatives for PNP-inhibitors
  作者：Sadao Hikishima、Machiko Isobe、Satoru Koyanagi、Shinji Soeda、Hiroshi Shimeno、Shiroshi Shibuya、Tsutomu Yokomatsu

  DOI：10.1016/j.bmc.2005.10.017

  日期：2006.3

  9-(5',5'-Difluoro-5'-phosphonopentyl)guanine (DFPP-G) and its hypoxanthine analogue (DFPP-H) were modified by introducing a methyl group to all possible positions of the linker connecting a purine and difluoromethylenephosphonic acid moiety to evaluate the effects of the methyl group on inhibition against purine nucleoside phosphorylase. The methyl group on the linker affected the inhibition in a positional-dependent manner. Inhibitory potency of alpha-methyl and beta-methyl -substituted analogues of DFPP-H increased by about 600- to 1000-fold upon converting to cyclopropane nucleotide analogue (+/-)-4. (c) 2005 Elsevier Ltd. All rights reserved.
• HALAZY, S.;EHRHARD, A.;DANZIN, C., J. AMER. CHEM. SOC., 113,(1991) N, C. 315-317
  作者：HALAZY, S.、EHRHARD, A.、DANZIN, C.

  DOI：——

  日期：——