formyl-3-dimethoxy-4,6-dimethyl-2,5-benzoate de methyle | 101908-84-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: formyl-3-dimethoxy-4,6-dimethyl-2,5-benzoate de methyle
• 英文别名: methyl 4,6-dimethoxy-2,5-dimethyl-3-formylbenzoate；methyl 5-formyl-2,4-dimethoxy-3,6-dimethylbenzoate
• CAS: 101908-84-3
• 化学式: C₁₃H₁₆O₅
• 分子量: 252.267
• InChiKey: JKFJUQJMEQAEGT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  18
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  formyl-3-dimethoxy-4,6-dimethyl-2,5-benzoate de methyle 在 吡啶 、 4-二甲氨基吡啶 、 氢氧化钾 、 sodium tetrahydroborate 、 草酰氯 、 三氟化硼乙醚 、 potassium carbonate 作用下， 以 二氯甲烷 、 二甲基亚砜 、 异丙醇 、 丙酮 、 甲苯 为溶剂， 反应 3.25h， 生成
  参考文献：
  名称：

  Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives

  摘要：

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.

  DOI：

  10.1021/jm960437a
• 作为产物：
  描述：

  methyl haematommate 在 盐酸 、 potassium carbonate 、 汞 、 三氟乙酸 、 锌 作用下， 以 甲醇 、 丙酮 为溶剂， 生成 formyl-3-dimethoxy-4,6-dimethyl-2,5-benzoate de methyle
  参考文献：
  名称：

  首次全合成抗肿瘤抗生素（±）-间硫霉素

  摘要：

  The first total synthesis of (+/-)-resorthiomycin, an antitumor antibiotic has been achieved. (C) 1999 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0040-4039(99)01015-1

文献信息

• Synthesis and biological evaluation of thielocin B1 analogues as protein-protein interaction inhibitors of PAC3 homodimer
  作者：Kosuke Ohsawa、Masahito Yoshida、Miho Izumikawa、Motoki Takagi、Kazuo Shin-ya、Naoki Goshima、Takatsugu Hirokawa、Tohru Natsume、Takayuki Doi

  DOI：10.1016/j.bmc.2018.11.001

  日期：2018.12

  The synthesis and biological evaluation of thielocin B1 analogues have been demonstrated. Fourteen analogues modified in the central core and terminal carboxylic acid moiety were concisely synthesized by simple esterification or etherification reaction. The evaluation of synthetic analogues as inhibitors of proteasome assembling chaperone (PAC) complexes (the PAC3 homodimer and PAC1/PAC2) revealed

  Thielocin B1类似物的合成和生物学评估已得到证实。通过简单的酯化或醚化反应简明地合成了在中心核和末端羧酸部分中修饰的十四个类似物。对作为蛋白酶体组装伴侣（PAC）复合物（PAC3同型二聚体和PAC1 / PAC2）抑制剂的合成类似物的评估表明，类似天然产物的弯曲结构和末端羧酸基团对其生物学活性至关重要。此外，SAR和计算机对接研究表明，Thielocin B1的二苯醚部分上的所有甲基均通过疏水作用对PAC3同型二聚体产生有效和选择性的抑制作用。
• A Direct and Mild Formylation Method for Substituted Benzenes Utilizing Dichloromethyl Methyl Ether–Silver Trifluoromethanesulfonate
  作者：Kosuke Ohsawa、Masahito Yoshida、Takayuki Doi

  DOI：10.1021/jo400056k

  日期：2013.4.5

  A silver trifluoromethanesulfonate (AgOTf)-promoted direct and mild formylation of benzenes has been developed. The reaction utilizing dichloromethyl methyl ether (Cl2CHOMe) and AgOTf powerfully formylated various substituted benzenes under temperature conditions as low as −78 °C without losing the protecting groups on the phenolic hydroxyl group.

  已经开发了三氟甲磺酸银（AgOTf）促进的苯的直接和温和甲酰化。利用二氯甲基甲基醚（Cl 2 CHOMe）和AgOTf的反应在低至-78°C的温度条件下将各种取代的苯甲酸酯化，而不会丢失酚羟基上的保护基。
• Synthèse d'une nouvelle depsidone dérivée de l'acide furfurique, le diméthoxy-3,8-(diméthoxy-2,4-méthoxycarbonyl-5-diméthyl-3,6-benzyl)-9-triméthyl-1,4,6-oxo-11-11<i>H</i>-dibenzo[<i>b</i>,<i>e</i>]dioxépinne[1,4]carboxylate-7 de méthyle
  作者：Jan Gunzinger、Raffaele Tabacchi

  DOI：10.1002/hlca.19850680719

  日期：1985.11.13

  Synthesis of a New Depsidone, Derivative of Furfuric Acid: Methyl 3,6-dimethoxy-9-(2,4-dimethoxy-5-methoxycarbonyl-3,6-dimethylbenzyl)-1,4,6-trimethyl-11-oxo-11H-dibenzo[b,e] [1,4]dioxepin-7-carboxylate

  糠酸衍生物新的二甲泼酮的合成：3,6-二甲氧基-9-（2,4-二甲氧基-5-甲氧基羰基-3,6-二甲基苄基）-1,4,6-三甲基-11-氧代甲基11 H-二苯并[ b，e ] [1,4]二氧杂-7-羧酸盐
• GUNZINGER, J.;TABACCHI, R., HELV. CHIM. ACTA, 1985, 68, N 7, 1940-1947
  作者：GUNZINGER, J.、TABACCHI, R.

  DOI：——

  日期：——
• Synthesis and Phospholipase A₂ Inhibitory Activity of Thielocin B3 Derivatives
  作者：Isao Teshirogi、Shigeru Matsutani、Kazuhiro Shirahase、Yasuhiko Fujii、Tadashi Yoshida、Kazushige Tanaka、Mitsuaki Ohtani

  DOI：10.1021/jm960437a

  日期：1996.1.1

  We prepared several types of derivatives of thielocin B3, a very potent naturally occurring inhibitor for human nonpancreatic secretory PLA(2) (sPLA(2)-II), and conducted a structure-activity relationship study to identify potent sPLA(2)-II inhibitors with the aim of developing antiinflammatory drugs. The total number of aromatic rings is critical for sPLA(2)-II inhibition, and the best result was obtained in the case of six rings. The structure of the central part of the inhibitors was not specific, and potent inhibitors were found among the sulfide, sulfone, ether, methylene, and amino derivatives. Although a diester of the terminal carboxylic acid lost its inhibitory activity, having both of the carboxylic acids was not necessary for expression of activity, as illustrated by a glycine derivative with the benzyl ester group 36. Among the newly synthesized derivatives, 18, 20, 29, and 36 showed very potent human sPLA(2)-II inhibitory activity comparable to that of natural thielocin B3. Their IC50 values are in the range 0.069-0.14 mu M, and they are a class of compounds showing the most potent sPLA(2)-II inhibition to date.