methyl 2-bromo-2-(diethoxyphosphoryl)acetate | 23755-72-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物
• 英文名称: methyl 2-bromo-2-(diethoxyphosphoryl)acetate
• 英文别名: methyl 2-bromo-2-diethoxyphosphorylacetate
• CAS: 23755-72-8
• 化学式: C₇H₁₄BrO₅P
• 分子量: 289.063
• InChiKey: MOHPUZYQUKUFEG-UHFFFAOYSA-N

物化性质

• 沸点：
  142-147 °C(Press: 3 Torr)
• 密度：
  1.3985 g/cm3

计算性质

• 辛醇/水分配系数(LogP)：
  2.15
• 重原子数：
  14.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  61.83
• 氢给体数：
  0.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  3,5,7-环庚三烯-1,3-二甲醛 、 methyl 2-bromo-2-(diethoxyphosphoryl)acetate 在 十六烷基三丁基溴化磷 sodium hydroxide 作用下， 以 二氯甲烷 为溶剂， 生成 (Z)-2-Bromo-3-(6-formyl-cyclohepta-1,3,5-trienyl)-acrylic acid methyl ester
  参考文献：
  名称：

  Sarmah, Chandra Sekhar; Kataky, J. C. S., Indian Journal of Chemistry - Section B Organic and Medicinal Chemistry, 1993, vol. 32, # 11, p. 1149 - 1150

  摘要：

  DOI：
• 作为产物：
  描述：

  膦酰基乙酸甲酯二乙酯 在 正丁基锂 、 溴 作用下， 以 乙二醇二甲醚 、 正己烷 为溶剂， 反应 2.08h， 以70%的产率得到methyl 2-bromo-2-(diethoxyphosphoryl)acetate
  参考文献：
  名称：

  通用铱催化还原二烯胺合成允许通过难以捉摸的脱氢可可丁五步合成长春质

  摘要：

  开发了一种用于功能化异奎宁环的立体和区域选择性合成的新还原策略。以化学选择性铱(I)催化的β,γ-不饱和δ-内酰胺还原活化为中心，高效生产的反应性二烯胺中间体很容易与各种亲二烯体发生[4 + 2]环加成反应，从而形成桥联双环胺产品。这种新的合成方法扩展到脂肪族起始原料，从而有效形成环己烯胺产品，并很容易作为迄今为止最短（五步）长春花生物碱长春质全合成的关键步骤，通过其难以捉摸的生物合成前体进行、脱氢可可定。

  DOI：

  10.1021/jacs.1c04980

文献信息

• Synthesis of a versatile metacyclophane macrolactam
  作者：Mingwen Wang、Brian S.J. Blagg

  DOI：10.1016/j.tetlet.2007.10.150

  日期：2008.1

  geldanamycin and the resorcinol moiety of radicicol, molecules have been produced that are highly effective inhibitors of the Hsp90 protein folding machinery. These chimeric inhibitors contain metacyclophane macrolactams that are difficult to cyclize and modify for incorporation of functional diversity. To circumvent this problem, a highly diversifiable alpha-bromo-alpha,beta-unsaturated ester has

  由于 Hsp90 已成为开发癌症化学治疗剂的有希望的靶点，因此需要对天然产物抑制剂和这种分子伴侣之间的构效关系进行系统评估。利用我们的嵌合体方法，它包含格尔德霉素的醌部分和根癌菌素的间苯二酚部分，已生产出作为 Hsp90 蛋白质折叠机制的高效抑制剂的分子。这些嵌合抑制剂包含难以环化和修饰以纳入功能多样性的间环芳烷大环内酰胺。为了规避这个问题，已经制备了高度多样化的α-溴-α，β-不饱和酯，这允许引入各种功能，从而能够阐明嵌合化合物和 Hsp90 之间的构效关系。本文报道了这种分子的基本原理、合成和优化。
• Application of Dually Activated Michael Acceptor to the Rational Design of Reversible Covalent Inhibitor for Enterovirus 71 3C Protease
  作者：Yuying Ma、Linfeng Li、Shuai He、Chengyou Shang、Yang Sun、Ning Liu、Thomas D. Meek、Yaxin Wang、Luqing Shang

  DOI：10.1021/acs.jmedchem.9b00387

  日期：2019.7.11

  Targeted covalent inhibitors (TCIs) have attracted growing attention from the pharmaceutical industry in recent decades because they have potential advantages in terms of efficacy, selectivity, and safety. TCIs have recently evolved into a new version with reversibility that can be systematically modulated. This feature may diminish the risk of haptenization and help optimize the drug-target residence time as needed. The enteroviral 3C protease (3C(pro)) is a valuable therapeutic target, but the development of 3C(pro) inhibitors is far from satisfactory. Therefore, we aimed to apply a reversible TCI approach to the design of novel 3C(pro) inhibitors. The introduction of various substituents onto the alpha-carbon of classical Michael acceptors yielded inhibitors bearing several classes of warheads. Using steady-state kinetics and biomolecular mass spectrometry, we confirmed the mode of reversible covalent inhibition and elucidated the mechanism by which the potency and reversibility were affected by electronic and steric factors. This research produced several potent inhibitors with good selectivity and suitable reversibility; moreover, it validated the reversible TCI approach in the field of viral infection, suggesting broader applications in the design of reversible covalent inhibitors for other proteases.
• Grinev,G.V. et al., Journal of general chemistry of the USSR, 1969, vol. 39, p. 1223 - 1225
  作者：Grinev,G.V. et al.

  DOI：——

  日期：——
• Nickel-promoted cyclization/carbonylation in the preparation of .alpha.-methylene-.gamma.lactones. Stereospecific synthesis of (.+-.)-frullanolide
  作者：M. F. Semmelhack、Steven J. Brickner

  DOI：10.1021/ja00403a065

  日期：1981.7
• Sekhar Sarmah Chandra, Kataky J. C. S., Indian J. Chem. B, 32 (1993) N 11, S 1149-1150
  作者：Sekhar Sarmah Chandra, Kataky J. C. S.

  DOI：——

  日期：——