(E)-4-(tert-butyldimethylsilanyloxy)-3-methylbut-2-enoic acid ethyl ester | 132032-94-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (E)-4-(tert-butyldimethylsilanyloxy)-3-methylbut-2-enoic acid ethyl ester
• 英文别名: (E)-4-(tert-butyldimethylsilyloxy)-3-methyl-but-2-enoic acid ethyl ester；Ethyl (e)-4-((tert-butyldimethylsilyl)oxy)-3-methylbut-2-enoate；ethyl (E)-4-[tert-butyl(dimethyl)silyl]oxy-3-methylbut-2-enoate
• CAS: 132032-94-1
• 化学式: C₁₃H₂₆O₃Si
• 分子量: 258.433
• InChiKey: DVJJUEGMGOLPBA-PKNBQFBNSA-N

物化性质

• 沸点：
  289.1±23.0 °C(Predicted)
• 密度：
  0.915±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.52
• 重原子数：
  17
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (E)-4-(tert-butyldimethylsilanyloxy)-3-methylbut-2-enoic acid ethyl ester 在 四溴化碳 、 二异丁基氢化铝 、 三苯基膦 作用下， 以 正己烷 、 二氯甲烷 、 甲苯 为溶剂， 反应 8.5h， 生成 (E)-4-(t-butyldimethylsilyloxy)-3-methyl-but-2-enyl bromide
  参考文献：
  名称：

  Replacing the pyrophosphate group of HMB-PP by a diphosphonate function abrogates Its potential to activate human γδ T cells but does not lead to competitive antagonism

  摘要：

  The immunological characterization of (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), and its methylenediphosphonate analogue, HMB-PCP, is described. With an EC50 of 0.1-0.2 nM, HMB-PP is significantly more potent in stimulating human Vgamma9/Vdelta2 T cells than any other compound described so far. However, replacing the pyrophosphate by a P-CH2-P function abrogates the bioactivity drastically, with HMB-PCP having a EC50 of only 5.3 muM. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(03)00138-0
• 作为产物：
  描述：

  L-(+)-酒石酸二乙酯 在 咪唑 、 sodium tetrahydroborate 、 NaIO₄ on SiO₂ 、 cerium(III) chloride heptahydrate 作用下， 以 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 生成 (E)-4-(tert-butyldimethylsilanyloxy)-3-methylbut-2-enoic acid ethyl ester
  参考文献：
  名称：

  Inhibition of IspH, a [4Fe–4S]²⁺ Enzyme Involved in the Biosynthesis of Isoprenoids via the Methylerythritol Phosphate Pathway

  摘要：

  The MEP pathway, which is absent in animals but present in most pathogenic bacteria, in the parasite responsible for malaria and in plant plastids, is a target for the development of antimicrobial drugs. IspH, an oxygen-sensitive [4Fe-4S] enzyme, catalyzes the last step of this pathway and converts (E)-4-hydroxy-3-methylbut-2-en-1-yl diphosphate (HMBPP) into the two isoprenoid precursors: isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP). A crucial step in the mechanism of this enzyme is the binding of the C4 hydroxyl of HMBPP to the unique fourth iron site in the [4Fe-4S](2+) moiety. Here, we report the synthesis and the kinetic investigations of two new extremely potent inhibitors of E. coli IspH where the OH group of HMBPP is replaced by an amino and a thiol group. (E)-4-Mercapto-3-methylbut-2-en-1-yl diphosphate is a reversible tight-binding inhibitor of IspH with K-i = 20 +/- 2, nM. A detailed kinetic analysis revealed that (E)-4-amino-3-methylbut-2-en-1-yl diphosphate is a reversible slow-binding inhibitor of IspH with K-i = 54 +/- 19 nM. The slow binding behavior of this inhibitor is best described by a one-step mechanism with the slow step consisting of the formation of the enzyme-inhibitor (EI) complex.

  DOI：

  10.1021/ja309557s

文献信息

• Total synthesis of (±)-acetoxyodontoschismenol using zirconium chemistry
  作者：Ian R. Baldwin、Richard J. Whitby

  DOI：10.1039/b309848f

  日期：——

  The dolabellane diterpene (+/-)-acetoxyodontoschismenol has been synthesised for the first time by a short route in which a three component coupling on zirconium is used to assemble all the carbons needed for the skeleton in onepot.

  多标签二萜（+/-）-乙酰氧基dontoschismenol已通过短途径首次合成，其中使用锆上的三组分偶联将骨架所需的所有碳组装到一个锅中。
• Synthesis and Biological Activity of Novel Acyclic Versions of NeplanocinA
  作者：Ying Wu、Joon Hee Hong

  DOI：10.1002/ardp.200500154

  日期：2005.11

  Novel acyclic Neplanocin A analogues were designed and synthesized. The coupling of the alkyl bromide 6 with nucleosidic bases (T, U, 5‐FU, 5‐IU, C, A) and desilylation afforded a series of novel acyclic nucleosides. The synthesized compounds 13–18 were evaluated for their antiviral and antitumor activity.

  设计并合成了新型无环 Neplanocin A 类似物。烷基溴 6 与核苷碱基 (T, U, 5-FU, 5-IU, C, A) 的偶联和脱甲硅烷基化提供了一系列新的无环核苷。评价合成的化合物 13-18 的抗病毒和抗肿瘤活性。
• Cobalt(II)-Azabis(oxazoline)-Catalyzed Conjugate Reduction of ?,?-Unsaturated Carbonyl Compounds
  作者：Christian Geiger、Peter Kreitmeier、Oliver Reiser

  DOI：10.1002/adsc.200404295

  日期：2005.2

  Azabis(oxazolines) prove to be superior ligands for the enantioselective, cobalt(II)-catalyzed conjugate reduction of α,β-unsaturated carbonyl compounds with sodium borohydride. β-Trisubstituted α,β-unsaturated esters and amides as well as γ-butenolides are readily converted to their corresponding saturated counterparts with enantioselectivities up to 97% ee.

  氮杂双（恶唑啉）被证明是对映选择性，钴（II）催化的硼氢化钠对α，β-不饱和羰基化合物的共轭还原反应的优良配体。β-三取代的α，β-不饱和酯和酰胺以及γ-丁烯内酯很容易转化为相应的饱和对映体，对映选择性高达97％ee。
• Synthesis and Biological Evaluation of (<i>E</i>)-4-Hydroxy-3-methylbut-2-enyl Phosphate (HMBP) Aryloxy Triester Phosphoramidate Prodrugs as Activators of Vγ9/Vδ2 T-Cell Immune Responses
  作者：Martin S. Davey、Roshni Malde、Rory C. Mykura、Alfie T. Baker、Taher E. Taher、Cécile S. Le Duff、Benjamin E. Willcox、Youcef Mehellou

  DOI：10.1021/acs.jmedchem.7b01824

  日期：2018.3.8

  The aryloxy triester phosphoramidate prodrug approach has been used with success in drug discovery. Herein, we describe the first application of this prodrug technology to the monophosphate derivative of the phosphoantigen HMBPP and one of its analogues. Some of these prodrugs exhibited specific and potent activation of Vγ9/Vδ2 T-cells, which were then able to lyse bladder cancer cells in vitro. This

  芳氧基三酯氨基磷酸酯前药方法已成功用于药物发现中。在这里，我们描述了这种前药技术在磷酸抗原HMBPP的单磷酸酯衍生物及其类似物中的首次应用。这些前药中的一些表现出Vγ9/Vδ2T细胞的特异性和有效激活，然后能够体外裂解膀胱癌细胞。这项工作凸显了这种前药技术在发现新型免疫疗法中的前景。
• Total Synthesis of (±)-Merrilactone A via Catalytic Nazarov Cyclization
  作者：Wei He、Jie Huang、Xiufeng Sun、Alison J. Frontier

  DOI：10.1021/ja068150i

  日期：2007.1.1

  The total synthesis of merrilactone A (a neurotrophic agent) has been achieved. In the approach reported, simultaneous creation of the C-4 and C-5 stereocenters was accomplished stereospecifically using an unprecedented variant of the Nazarov cyclization. Additional studies focused upon this Lewis acid-catalyzed cyclization of a silyloxyfuran-containing intermediate are presented.

  merrilactone A（一种神经营养剂）的全合成已经实现。在报道的方法中，C-4 和 C-5 立体中心的同时创建是使用前所未有的 Nazarov 环化变体立体定向完成的。其他研究集中在这种路易斯酸催化的含甲硅烷氧基呋喃中间体的环化上。