3-((tert-butyldimethylsilyl)oxy)-4-methoxybenzoic acid | 154083-41-7

• 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: 3-((tert-butyldimethylsilyl)oxy)-4-methoxybenzoic acid
• 英文别名: 3-(tert-butyl-dimethyl-silanyloxy)-4-methoxy-benzoic acid；3-(tert-Butyldimethylsilyloxy)-4-methoxybenzoic acid；3-[tert-butyl(dimethyl)silyl]oxy-4-methoxybenzoic acid
• CAS: 154083-41-7
• 化学式: C₁₄H₂₂O₄Si
• 分子量: 282.412
• InChiKey: HVNOUUOROXYLEH-UHFFFAOYSA-N

物化性质

• 熔点：
  163.5-164.5 °C
• 沸点：
  348.4±32.0 °C(Predicted)
• 密度：
  1.052±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.78
• 重原子数：
  19
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-((tert-butyldimethylsilyl)oxy)-4-methoxybenzoic acid 在 吡啶 、 三聚氟氰 作用下， 反应 2.5h， 以99%的产率得到3-((tert-butyldimethylsilyl)oxy)-4-methoxybenzoyl fluoride
  参考文献：
  名称：

  A-Ring Dihalogenation Increases the Cellular Activity of Combretastatin-Templated Tetrazoles

  摘要：

  The combretastatins have been investigated for their antimitotic and antivascular properties, and it is widely postulated that a 3,4,5-trimethoxyaryl A-ring is essential to maintain potent activity. We have synthesized new tetrazole analogues (32-34), demonstrating that 3,5-dihalogenation can consistently increase potency by up to 5-fold when compared to the equivalent trimethoxy compound on human umbilical vein endothelial cells (HUVECs) and a range of cancer cells. Moreover, this increased potency offsets that lost by installing the tetrazole bridge into combretastatin A-4 (1), giving crystalline, soluble compounds that have low nanomolar activity, arrest cells in G(2)/M phase, and retain microtubule inhibitory activity. Molecular modeling has shown that optimized packing within the binding site resulting in increased Coulombic interaction may be responsible for this improved activity.

  DOI：

  10.1021/ml200149g
• 作为产物：
  描述：

  异香兰素 在 咪唑 、 sodium chlorite 、 sodium dihydrogenphosphate 、 双氧水 作用下， 以 水 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 生成 3-((tert-butyldimethylsilyl)oxy)-4-methoxybenzoic acid
  参考文献：
  名称：

  首次完全合成两种新的杂环化合物：布雷西地那嗪A和B

  摘要：

  摘要报道了两种新的天然杂环化合物bretschneiderazines A（2）和B（3）的简便合成方法，该化合物是从中华小Bre（Bretschneidera sinensis）茎提取物中分离得到的。我们通过直接锂化和以硫和光气作为关键步骤的顺序处理，采用了苯甲酰胺的环化反应。所有新化合物均已通过IR，1 H NMR，13 C NMR和HRMS进行了全面表征。

  DOI：

  10.1016/j.cclet.2010.11.036

文献信息

• Antineoplastic Agents. 379. Synthesis of Phenstatin Phosphate^1a,
  作者：George R. Pettit、Brian Toki、Delbert L. Herald、Pascal Verdier-Pinard、Michael R. Boyd、Ernest Hamel、Robin K. Pettit

  DOI：10.1021/jm970644q

  日期：1998.5.1

  A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (1b) directed at maintaining the (Z)-stilbene relationship of the olefin diphenyl substituents led to synthesis of a potent cancer cell growth inhibitor designated phenstatin (3b). Initially phenstatin silyl ether (3a) was unexpectedly obtained by Jacobsen

  南非柳树（Combretum caffrum）抗肿瘤成分康维他汀A-4（1b）的结构-活性关系（SAR）研究旨在维持烯烃二苯基取代基的（Z）-二苯乙烯关系，导致合成了潜在的癌症细胞生长抑制剂称为phenstatin（3b）。最初通过康普他汀A-4甲硅烷基醚的雅各布森氧化（1c-> 3a）意外地获得了苯他汀甲硅烷基醚（3a），后来又在20℃下合成了母体苯他汀（3b）（6a-> 3a-> 3b）。数量。通过亚磷酸二苄酯的磷酸化和随后的氢解顺序（3b-> 3c-> 3d）将苯他汀类药物转化为磷酸钠前药（3d）。苯他汀（3b）抑制了致病菌奈瑟氏弧菌的生长，并且是微管蛋白聚合的有效抑制剂，秋水仙碱与微管蛋白的结合可与康维他汀A-4（1b）相提并论。有趣的是，在这些生化分析中发现前药的活性降低。尽管康普他汀A-4（1d）的磷酸化衍生物未观察到显着的微管蛋白活性，但在两种测定中磷酸盐3d均保留了可检测的抑制作用。
• Synthesis of non-steroidal 2-methoxyestradiol mimetics based on the bicyclo[3.3.1]nonane structural motif
  作者：Evgeniya V. Nurieva、Nikolay A. Zefirov、Alexandra V. Mamaeva、Yuri K. Grishin、Sergei A. Kuznetsov、Olga N. Zefirova

  DOI：10.1016/j.mencom.2017.05.007

  日期：2017.5

  Two pairs of bicyclo[3.3.1]nonane derivatives with 2-methoxyphenol moiety were synthesized as non-steroidal 2-methoxyestradiol mimetics demonstrating noticeable cytotoxicity to human lung carcinoma cell line A549. Compounds with 2-methoxyphenol annulated with bicyclo[3.3.1]nonane fragment were obtained using BF3-assisted oxirane opening in 5-(4-benzyloxy-3-methoxyphenyl)-1-oxaspiro[2.5]octanes with

  合成了两对具有2-甲氧基苯酚部分的双环[3.3.1]壬烷衍生物，作为非甾体的2-甲氧基雌二醇模拟物，证明其对人肺癌细胞系A549具有明显的细胞毒性。使用5-（4-苄氧基-3-甲氧基苯基）-1-氧螺环[2.5]辛烷中的BF3辅助环氧乙烷开口，同时进行分子内环化和还原，获得带有双环[3.3.1]壬烷片段环化的2-甲氧基苯酚的化合物关键步骤。将内-7-羟基双环[3.3.1]壬烷-exo-3-羧酸转化为在分子的酸或醇部分中含有2-甲氧基苯酚片段的两种酯。
• First total synthesis of two new heterocyclic compounds: Bretschneiderazines A and B
  作者：Qing Chao Liu、Tian Tian Guo、Zheng Fan、Dong Li、Wen Hong Li

  DOI：10.1016/j.cclet.2010.11.036

  日期：2011.7

  heterocyclic compounds bretschneiderazines A ( 2 ) and B ( 3 ), isolated from an extract of the stems of Bretschneidera sinensis , is reported. We employed the cyclization reaction of benzamide by directed lithiation and sequential treatment with sulfur and phosgene as key steps. All new compounds have been fully characterized by means of IR, 1 H NMR, 13 C NMR, and HRMS.

  摘要报道了两种新的天然杂环化合物bretschneiderazines A（2）和B（3）的简便合成方法，该化合物是从中华小Bre（Bretschneidera sinensis）茎提取物中分离得到的。我们通过直接锂化和以硫和光气作为关键步骤的顺序处理，采用了苯甲酰胺的环化反应。所有新化合物均已通过IR，1 H NMR，13 C NMR和HRMS进行了全面表征。
• Synthesis of phenstatin and prodrugs thereof
  申请人：Pettit George R.

  公开号：US06943194B1

  公开（公告）日：2005-09-13

  A newly discovered antineoplastic compound denominated “phenstatin” is herein described as are synthetic methods for producing phenstatin and the active prodrug thereof. Phenstatin was converted to the sodium phosphate prodrug (3d) by a dibenzylphosphite phosphorylation and subsequent hydrogenolysis sequence 3b→3c→3d. Phenstatin (3b) was found to be a potent inhibitor of tubulin polymerization and the binding of colchicine to tubulin comparable to combretastatin A-4 (1b).

  一种新发现的抗肿瘤化合物被命名为“苯基史达汀”，本文描述了生产苯基史达汀及其活性前药的合成方法。苯基史达汀通过二苯基磷酸酯磷酸化和随后的氢解序列3b→3c→3d 转化为磷酸钠前药（3d）。发现苯基史达汀（3b）是一种有效的微管聚合抑制剂，与考尔地西汀结合到微管上的能力与康伯雷司汀 A-4（1b）相当。
• Chemiluminescent electron-rich aryl-substituted 1,2-dioxetanes
  申请人：Abbott Laboratories

  公开号：US05603868A1

  公开（公告）日：1997-02-18

  Chemiluminescent electron-rich aryl-substituted 1,2-dioxetane compounds are disclosed in which the aryl group is poly-substituted with suitable electron-donating groups such that the light-emitting pattern of the molecule results in a very high luminescent count, thus providing for a sensitive and precise assay for haptens, analytes, polynucleotides and the like. These substituted aryl-containing 1,2-dioxetane compounds can be used as direct labels in an immunoassay or when derivatized with an appropriate leaving group, can be used as a substrate for a enzyme immunoassay. The unusual chemiluminescence of the compounds allows the timing of the luminescent reaction to be exactly controlled.

  揭示了含有芳基取代的化学发光富电子1,2-二氧杂环烷化合物，其中芳基通过适当的给电子基团多取代，使分子的发光模式呈现出非常高的发光计数，从而为半抗原、分析物、多核苷酸等提供了一种敏感且精确的测定方法。这些取代的含芳基1,2-二氧杂环烷化合物可以直接用作免疫测定中的标记物，或者当它们与适当的离去基团衍生化时，可以用作酶免疫测定的底物。这些化合物的异常化学发光使得发光反应的时间可以被精确控制。