(4-bromo-2-methoxyphenoxy)(tert-butyl)dimethylsilane | 149777-72-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: (4-bromo-2-methoxyphenoxy)(tert-butyl)dimethylsilane
• 英文别名: 2-tert-butyldimethylsiloxy-5-bromoanisole；1-Bromo-4-(tert-butyldimethylsilyloxy)-3-methoxybenzene；(4-bromo-2-methoxyphenoxy)-tert-butyl-dimethylsilane
• CAS: 149777-72-0
• 化学式: C₁₃H₂₁BrO₂Si
• 分子量: 317.298
• InChiKey: QMCJWKWEGJPWMG-UHFFFAOYSA-N

物化性质

• 沸点：
  302.1±32.0 °C(Predicted)
• 密度：
  1.166±0.06 g/cm3(Predicted)
• 保留指数：
  1750.5

计算性质

• 辛醇/水分配系数(LogP)：
  4.84
• 重原子数：
  17
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (4-bromo-2-methoxyphenoxy)(tert-butyl)dimethylsilane 在 lithium aluminium tetrahydride 、 叔丁基锂 作用下， 以 四氢呋喃 、 正戊烷 为溶剂， 反应 7.17h， 生成
  参考文献：
  名称：

  Evaluation of Manassantin A Tetrahydrofuran Core Region Analogues and Cooperative Therapeutic Effects with EGFR Inhibition

  摘要：

  Tumors adapt to hypoxia by regulating angiogenesis, metastatic potential, and metabolism. These adaptations mediated by hypoxia-inducible factor 1 (HIF-1) make tumors more aggressive and resistant to chemotherapy and radiation. Therefore, HIF-1 is a validated therapeutic target for cancer. In order to develop new HIF-1 inhibitors for cancer chemotherapy by harnessing the potential of the natural product manassantin A, we synthesized and evaluated manassantin A analogues with modifications in the tetrahydrofuran core region of manassantin A. Our structure-activity relationship study indicated that the alpha,alpha'-trans-configuration of the central ring of manassantin A is critical to HIF-1 inhibition. We also demonstrated that a combination of manassantin A with an epidermal growth factor receptor inhibitor shows cooperative antitumor activity (similar to 80% inhibition for combination vs similar to 30% inhibition for monotherapy). Our findings will provide important frameworks for the future therapeutic development of manassantin A-derived chemotherapeutic agents.

  DOI：

  10.1021/acs.jmedchem.0c00151
• 作为产物：
  描述：

  4-溴邻甲氧基苯酚 、 叔丁基二甲基氯硅烷 在 咪唑 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 以227 g的产率得到(4-bromo-2-methoxyphenoxy)(tert-butyl)dimethylsilane
  参考文献：
  名称：

  8,14-二氢吗啡二烯酮生物碱的全合成

  摘要：

  据报导了8，14-二氢去甲鲁氨啶，8，14-二氢去甲戊啶，正异青藤烯碱和异小青藤碱的集体合成。该策略提供了直接获得产品正确氧化水平的途径。有机催化剂胍超碱，叔胺碱和脱水剂的结合对于成功的亨利-迈克尔-脱水级联反应形成菲基是必要的。所需的选择性脂肪族硝基还原只能在非均相转移-氢化条件下实现。

  DOI：

  10.1021/ol500368p

文献信息

• Bioinspired total synthesis of tetrahydrofuran lignans by tandem nucleophilic addition/redox isomerization/oxidative coupling and cycloetherification reactions as key steps
  作者：Pratap R. Jagtap、Ivana Císařová、Ullrich Jahn

  DOI：10.1039/c7ob02848b

  日期：——

  A very short three-step approach to trans,trans,trans-2,5-diaryl-3,4-dimethyltetrahydrofuran lignans is reported. The carbon skeleton is assembled in a single step based on an unprecedented tandem reaction consisting of 1,2-addition of aryllithium reagents to α,β-unsaturated aldehydes, ruthenium-catalyzed redox isomerization of the resulting alkoxides to enolates and their dimerization triggered by

  据报道，反式，反式，反式-2,5-二芳基-3,4-二甲基四氢呋喃木脂素的非常短的三步法。碳骨架是基于空前的串联反应由一个步骤组装而成的，该串联反应由芳基锂试剂与α，β-不饱和醛的1,2-加成反应，钌催化的所得醇盐氧化还原异构化为烯醇化物以及它们的二聚反应引发。电子氧化。形成的2，3-二烷基-1，4-二酮具有中等至良好的d / l-非对映选择性，并通过还原和非对映选择性环醚化转化为目标四氢呋喃木脂素。
• Total Synthesis of 8,14-Dihydromorphinandienone Alkaloids
  作者：Bahman Ghavimi、Philip Magnus

  DOI：10.1021/ol500368p

  日期：2014.3.21

  14-dihydronorsalutaridine, 8,14-dihydrosalutaridine, norisosinomenine, and isosinomenine is reported. The strategy provides direct access to the correct oxidation level of the products. The combination of an organocatalyst guanidine superbase, a tertiary amine base, and a dehydrating agent was necessary for the successful Henry–Michael–dehydration cascade to form the phenanthrene motif. The required selective

  据报导了8，14-二氢去甲鲁氨啶，8，14-二氢去甲戊啶，正异青藤烯碱和异小青藤碱的集体合成。该策略提供了直接获得产品正确氧化水平的途径。有机催化剂胍超碱，叔胺碱和脱水剂的结合对于成功的亨利-迈克尔-脱水级联反应形成菲基是必要的。所需的选择性脂肪族硝基还原只能在非均相转移-氢化条件下实现。
• Kumada–Corriu Cross Coupling Route to the Anti-Cancer Agent Combretastatin A-4
  作者：Alejandro A. Camacho-Dávila

  DOI：10.1080/00397910802238692

  日期：2008.10.22

  Abstract A short and efficient synthesis of the anticancer agent combretastatin A-4 was accomplished from inexpensive starting materials using the iron-catalyzed cross-coupling of a Grignard reagent and a bromostilbene as the key step.

  摘要 以格氏试剂和溴二苯乙烯的铁催化交叉偶联为关键步骤，从廉价的起始材料中完成了抗癌剂考布他汀 A-4 的快速有效合成。
• Stereoselective Synthesis of Tetrahydrofuran Lignans via BF₃·OEt₂-Promoted Reductive Deoxygenation/Epimerization of Cyclic Hemiketal:  Synthesis of (−)-Odoratisol C, (−)-Futokadsurin A, (−)-Veraguensin, (+)-Fragransin A₂, (+)-Galbelgin, and (+)-Talaumidin
  作者：Hyoungsu Kim、Ceshea M. Wooten、Yongho Park、Jiyong Hong

  DOI：10.1021/ol7016388

  日期：2007.9.1

  A versatile route to the synthesis of 2,5-diaryl-3,4-dimethyltetrahydrofuran lignans, (-)-odoratisol C (1), (-)-futokadsurin A (2), (-)-veraguensin (3), (+)-fragransin A2 (4), (+)-galbelgin (5), and (+)-talaumidin (6), is described. Central to the synthesis of the lignans is BF(3) x OEt(2)-promoted deoxygenation/epimerization of the hemiketal 9a followed by stereoselective reduction of the oxocarbenium

  合成2,5-二芳基-3,4-二甲基四氢呋喃木脂素，（-）-香豆酚C（1），（-）-Futokadsurin A（2），（-）-veraguensin（3），（描述了+）-fragransin A2（4），（+）-galbelgin（5）和（+）-talaumidin（6）。木酚素合成的核心是BF（3）x OEt（2）促进半缩醛9a的脱氧/表观电子化，然后立体选择性还原氧碳鎓离子中间体8a，b。
• Discovery of CAPE derivatives as dual EGFR and CSK inhibitors with anticancer activity in a murine model of hepatocellular carcinoma
  作者：Xiaoyu Liu、Qianqian Du、Caiping Tian、Mei Tang、Yingjun Jiang、Yong Wang、Yang Cao、Zhe Wang、Zhenwei Wang、Jing Yang、Yan Li、Xiaozhen Jiao、Ping Xie

  DOI：10.1016/j.bioorg.2020.104536

  日期：2021.2

  Thiol Reactivity Profiling), epidermal growth factor receptor (EGFR) and C-terminal Src kinase (CSK) were supposed to the targets of 8f, which was confirmed by binding mode analysis. Furthermore, compounds 8f, 8l, 8j, 8k, 8g, and 8h showed potent inhibitory effects against both CSK and EGFR than other derivatives in an ADP-Glo™ kinase assay. The representative compound, 8f, potently inhibited various

  咖啡酸苯乙酯（CAPE）是一种从蜂巢蜂胶中提取的生物活性成分，可以抑制肝细胞癌（HCC）。为了探索更稳定的 CAPE 衍生物，设计、合成了 25 种化合物，并进行了体外和体内药理学评估，作为 HCC 的抗肿瘤剂。化合物8d、8f、8l、8j和8k在HCC细胞系中显示出比包括CAPE在内的其他化合物有利的抗增殖活性。根据QTRP（Quantitative Thiol Reactivity Profiling）的结果，表皮生长因子受体（EGFR）和C端Src激酶（CSK）被认为是8f的靶标，这通过结合模式分析得到证实。此外，在 ADP-Glo​​™ 激酶测定中，化合物8f、8l、8j、8k、8g和8h对 CSK 和 EGFR 均显示出强于其他衍生物的抑制作用。代表性化合物8f有效抑制小鼠模型中的各种肿瘤生长，包括小鼠肝细胞癌 H22，同时下调 EGFR/AKT 通路并通过抑制 CSK 增强 T