bromomethyl butyrate | 186145-41-5

• 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: bromomethyl butyrate
• 英文别名: butyryloxymethyl bromide；bromomethyl butanoate
• CAS: 186145-41-5
• 化学式: C₅H₉BrO₂
• 分子量: 181.029
• InChiKey: KSBKJOHUPSXBMP-UHFFFAOYSA-N

物化性质

• 沸点：
  167.2±23.0 °C(Predicted)
• 密度：
  1.417±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  8
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  Phosphoric acid mono-((1R,2R,3S,4R,5R,6S)-2,3,6-tris-benzyloxy-4,5-bis-phosphonooxy-cyclohexyl) ester 、 bromomethyl butyrate 在 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 48.0h， 以29.4 mg的产率得到(-)-1D-2,3,6-tris-O-benzyl-myo-inositol 1,4,5-triphosphate hexakis(butyryloxymethyl) ester
  参考文献：
  名称：

  The Synthesis of Membrane Permeant Derivatives of myo-Inositol 1,4,5-Trisphosphate

  摘要：

  为了能够研究细胞内的第二信使 d-肌醇-1,4,5-三磷酸腺苷（InsP3）及其受体（InsP3Rs），人们希望开发出受保护的 InsP3 衍生物，这种衍生物能够在细胞外应用时进入细胞。随后，细胞内的酶会去除亲脂性保护基团，释放出 InsP3，从而激活 InsP3R。报告了两种 d-肌醇 1,4,5-三磷酸己二异（丁酰氧基甲基）酯（d-InsP3/BM）和一种 l-InsP3/BM的合成。研究表明，细胞外施用 d-对映体会导致 Ca2+ 释放，这被认为是通过 InsP3Rs 发生的。应用 l-对映体则几乎没有 Ca2+ 释放。

  DOI：

  10.1071/ch06357
• 作为产物：
  描述：

  methylene dibutyrate 在 三甲基溴硅烷 、 zinc dibromide 作用下， 以48.2%的产率得到bromomethyl butyrate
  参考文献：
  名称：

  The Synthesis of Membrane Permeant Derivatives of myo-Inositol 1,4,5-Trisphosphate

  摘要：

  为了能够研究细胞内的第二信使 d-肌醇-1,4,5-三磷酸腺苷（InsP3）及其受体（InsP3Rs），人们希望开发出受保护的 InsP3 衍生物，这种衍生物能够在细胞外应用时进入细胞。随后，细胞内的酶会去除亲脂性保护基团，释放出 InsP3，从而激活 InsP3R。报告了两种 d-肌醇 1,4,5-三磷酸己二异（丁酰氧基甲基）酯（d-InsP3/BM）和一种 l-InsP3/BM的合成。研究表明，细胞外施用 d-对映体会导致 Ca2+ 释放，这被认为是通过 InsP3Rs 发生的。应用 l-对映体则几乎没有 Ca2+ 释放。

  DOI：

  10.1071/ch06357

文献信息

• Membrane-permeant esters of inositol polyphosphates, chemical syntheses and biological applications
  作者：Wenhong Li、Carsten Schultz、Juan Llopis、Roger Y. Tsien

  DOI：10.1016/s0040-4020(97)00714-x

  日期：1997.9

  inositol polyphosphates are useful tools for biological studies. Racemic 2,3,6-tri-O-butyryl-myo-inositol 1,4,5-trisphosphate hexakis(acetoxymethyl) ester(), myo-inositol 1,4,5-trisphosphate hexakis(acetoxymethyl) ester (), hexakis(propionyloxymethyl) ester () and hexakis(butyryloxymethyl) ester () were therefore synthesized. Whereas extracellular application of up to 200 μM of or to 1321N1 astrocytoma

  肌醇多磷酸的膜渗透性衍生物是用于生物学研究的有用工具。外消旋2,3,6-三-O-丁酰基肌肌醇1,4,5-三磷酸六（乙酰氧基甲基）酯（），肌醇肌醇1,4,5-三磷酸六（乙酰氧基甲基）酯（），六因此合成了（丙酰氧基甲基）酯（）和六（丁酰氧基甲基）酯（）。而最多200μM或1321N1星形细胞瘤细胞的细胞外应用未能动员内部钙，并分别以低至20μM和2μM的浓度释放内部钙。
• Synthesis and use of cell-permeant cyclic ADP-ribose
  作者：Daniel Rosen、Duncan Bloor-Young、James Squires、Raman Parkesh、Gareth Waters、Sridhar R. Vasudevan、Alexander M. Lewis、Grant C. Churchill

  DOI：10.1016/j.bbrc.2012.01.025

  日期：2012.2

  Cyclic ADP-ribose (cADPR) is a second messenger that acts on ryanodine receptors to mobilize Ca2+. cADPR has a net negative charge at physiological pH making it not passively membrane permeant thereby requiring it to be injected, electroporated or loaded via liposomes. Such membrane impermeance of other charged intracellular messengers (including cyclic AMP, inositol 1,4,5-trisphosphate and nicotinic acid adenine dinucleotide phosphate) and fluorescent dyes (including fura-2 and fluorescein) has been overcome by synthesizing masked analogs (prodrugs), which are passively permeant and hydrolyzed to the parent compound inside cells. We now report the synthesis and biological activity of acetoxymethyl (AM) and butoxymethyl (BM) analogs of cADPR. Extracellular addition of cADPR-AM or cADPR-BM to neuronal cells in primary culture or PC12 neuroblastoma cells induced increases in cytosolic Ca2+. Pre-incubation of PC12 cells with thapsigargin, ryanodine or caffeine eliminated the response to cADPR-AM, whereas the response still occurred in the absence of extracellular Ca2+. Combined, these data demonstrate that masked cADPR analogs are cell-permeant and biologically active. We hope these cell-permeant tools will facilitate cADPR research and reveal its diverse physiological functions. (C) 2012 Elsevier Inc. All rights reserved.
• Anti-cancer activity of the cell membrane-permeable phytic acid prodrug
  作者：Takuya Masunaga、Naoki Murao、Hiroshi Tateishi、Ryoko Koga、Takeo Ohsugi、Masami Otsuka、Mikako Fujita

  DOI：10.1016/j.bioorg.2019.103240

  日期：2019.11

  Phytic acid (IP6) is an ingredient in cereals and legumes, and limited amounts of this compound are considered to enter the cell and exert anti-cancer effects. These effects have been seen by studying cells treated with around 1-5 mM IP6. However, such a large amount of IP6 chelates metals and changes the pH in cell culture medium. To overcome this problem, we synthesized a prodrug of IP6 (Pro-IP6) and elucidated generation of IP6 from Pro-IP6 in cells. Cellular experiments using Pro-IP6 demonstrated selective anti-cancer effects including apoptosis and inhibition of Akt activation. Furthermore, an in vivo study using mice with adult T-cell leukemia also showed that Pro-IP6 reduced the size of the cancer. Taken together, Pro-IP6 is a useful biological tool and may lead to development of new anti-cancer drugs.
• The Synthesis of Membrane Permeant Derivatives of myo-Inositol 1,4,5-Trisphosphate
  作者：Stuart J. Conway、Jan W. Thuring、Sylvain Andreu、Brynn T. Kvinlaug、H. Llewelyn Roderick、Martin D. Bootman、Andrew B. Holmes

  DOI：10.1071/ch06357

  日期：——

  In order to enable the study of the intracellular second messenger d-myo-inositol 1,4,5-trisphosphate (InsP3) and its receptors (InsP3Rs), it has been desirable to develop protected derivatives of InsP3 that are able to enter the cell, upon extracellular application. The subsequent removal of the lipophilic protecting groups, by intracellular enzymes, releases InsP3 and leads to the activation of InsP3Rs. Two syntheses of d-myo-inositol 1,4,5-trisphosphate hexakis(butyryloxymethyl) ester (d-InsP3/BM) and one of l-InsP3/BM are reported. It is demonstrated that extracellular application of the d-enantiomer results in Ca2+ release, which is thought to occur via InsP3Rs. Application of the l-enantiomer resulted in little Ca2+ release.

  为了能够研究细胞内的第二信使 d-肌醇-1,4,5-三磷酸腺苷（InsP3）及其受体（InsP3Rs），人们希望开发出受保护的 InsP3 衍生物，这种衍生物能够在细胞外应用时进入细胞。随后，细胞内的酶会去除亲脂性保护基团，释放出 InsP3，从而激活 InsP3R。报告了两种 d-肌醇 1,4,5-三磷酸己二异（丁酰氧基甲基）酯（d-InsP3/BM）和一种 l-InsP3/BM的合成。研究表明，细胞外施用 d-对映体会导致 Ca2+ 释放，这被认为是通过 InsP3Rs 发生的。应用 l-对映体则几乎没有 Ca2+ 释放。