2-(4-tert-butyldimethylsilanyloxy-3-methoxyphenyl)-1,3-dithiane | 877438-30-7

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(4-tert-butyldimethylsilanyloxy-3-methoxyphenyl)-1,3-dithiane
• 英文别名: Tert-butyl-[4-(1,3-dithian-2-yl)-2-methoxyphenoxy]-dimethylsilane
• CAS: 877438-30-7
• 化学式: C₁₇H₂₈O₂S₂Si
• 分子量: 356.626
• InChiKey: KZBWMMCDXNEXPU-UHFFFAOYSA-N

物化性质

• 沸点：
  424.0±45.0 °C(Predicted)
• 密度：
  1.061±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.95
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  69.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(4-tert-butyldimethylsilanyloxy-3-methoxyphenyl)-1,3-dithiane 在 氢氧化钾 、 sodium tetrahydroborate 、 正丁基锂 、 水 、 L-Selectride 、 [双(三氟乙酰氧基)碘]苯 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 正己烷 、 乙腈 为溶剂， 反应 10.5h， 生成 (7'R,8R,8'R)-4,4'-bis(tert-butyldimethylsilanyloxy)-7'-hydroxy-3,3'-dimethoxylignano-9,9'-lactone
  参考文献：
  名称：

  天然存在的7'-羟基木质素-9,9'-内酯的不对称合成，立体化学和重排反应。

  摘要：

  提出了一系列（7'S，8R，8'R）-7'-hydroxylignano-9,9'-内酯的不对称合成，其中包括哺乳动物的木脂素（7'S）-羟基对映体内酯和（7'S）-对羟基苯甲酸酯。天然存在的（-）-对羟基苯甲酸酯的立体化学有待重新分配。羟基内酯重排及其可能的机制进行了讨论。最后，简要介绍了7'-羟基木质素-9,9'-内酯的当前命名和编号变体，并提出了统一术语的建议。

  DOI：

  10.1039/b513303c
• 作为产物：
  描述：

  香草醛 在 咪唑 、 4-二甲氨基吡啶 、 碘 作用下， 以 二氯甲烷 为溶剂， 反应 24.0h， 生成 2-(4-tert-butyldimethylsilanyloxy-3-methoxyphenyl)-1,3-dithiane
  参考文献：
  名称：

  Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes

  摘要：

  The autoxidative condensation of 2-aryl-2-lithio-1,3-dithianes is here reported. Treatment of 2-aryl-1,3-dithianes with n-BuLi in the absence of any electrophile leads to condensation of three molecules of 1,3-dithianes and formation of highly functionalized α-thioether ketones orthothioesters in 51-89% yields upon air exposure. The method was further expanded to benzaldehyde dithioacetals, affording corresponding orthothioesters and α-thioether ketones in 48-97% yields. The experimental results combined with density functional theory studies support a mechanism triggered by the autoxidation of 2-aryl-2-lithio-1,3-dithianes to yield a highly reactive thioester that undergoes condensation with two other molecules of 2-aryl-2-lithio-1,3-dithiane.

  DOI：

  10.1021/acs.joc.7b02896

文献信息

• Battling Glioblastoma: A Novel Tyrosine Kinase Inhibitor with Multi-Dimensional Anti-Tumor Effect
  作者：Anisha Viswanathan、Aliyu Musa、Akshaya Murugesan、João Vale、Carlos Afonso、Saravanan Konda Mani、Olli Yli-Harja、Nuno Candeias、Meenakshisundaram Kandhavelu

  DOI：10.3390/cells8121624

  日期：——

  Glioblastoma (GB), a grade IV glioma, with high heterogeneity and chemoresistance, obligates a multidimensional antagonist to debilitate its competence. Considering the previous reports on thioesters as antitumor compounds, this paper investigates on use of this densely functionalized sulphur rich molecule as a potent anti-GB agent. Bio-evaluation of 12 novel compounds, containing α-thioether ketone and orthothioester functionalities, identified that five analogs exhibited better cytotoxic profile compared to standard drug cisplatin. Detailed toxicity studies of top compound were evaluated in two cell lines, using cell viability test, apoptotic activity, oxidative stress and caspase activation and RNA-sequencing analysis, to obtain a comprehensive molecular profile of drug activity. The most effective molecule presented half maximal inhibitory concentration (IC50) values of 27 μM and 23 μM against U87 and LN229 GB cells, respectively. Same compound effectively weakened various angiogenic pathways, mainly MAPK and JAK-STAT pathways, downregulating VEGF. Transcriptome analysis identified significant promotion of apoptotic genes, and genes involved in cell cycle arrest, with concurrent inhibition of various tyrosine kinase cascades and stress response genes. Docking and immunoblotting studies suggest EGFR as a strong target of the orthothioester identified. Therefore, orthothioesters can potentially serve as a multi-dimensional chemotherapeutic possessing strong cytotoxic, anti-angiogenic and chemo-sensitization activity, challenging glioblastoma pathogenesis.

  胶质母细胞瘤（GB），一种高度异质性和化疗抵抗性的四级胶质瘤，需要多维对抗剂来削弱其竞争力。考虑到之前关于硫酯类化合物作为抗肿瘤化合物的报告，本文调查了这种功能丰富的硫含量丰富的分子作为一种有效的抗GB剂的用途。对包含α-硫醚酮和正硫酯功能的12种新化合物进行生物评价，发现其中五种类似物相比标准药物顺铂表现出更好的细胞毒性特征。对最佳化合物的详细毒性研究在两种细胞系中进行了评估，使用细胞存活率测试、凋亡活性、氧化应激和caspase激活以及RNA测序分析，以获得药物活性的全面分子特征。最有效的分子在U87和LN229 GB细胞中的半数最大抑制浓度（IC50）值分别为27μM和23μM。相同的化合物有效地削弱了各种血管生成途径，主要是MAPK和JAK-STAT途径，降低了VEGF的表达。转录组分析确定了凋亡基因的显着促进，以及参与细胞周期阻滞的基因，同时抑制了各种酪氨酸激酶级联和应激反应基因。对接和免疫印迹研究表明EGFR是正硫酯酯的一个强大靶点。因此，正硫酯酯有望作为一种具有强烈细胞毒性、抗血管生成和化疗敏感性活性的多维化疗药物，挑战胶质母细胞瘤的发病机制。
• Total syntheses of schizandriside, saracoside and (±)-isolariciresinol with antioxidant activities
  作者：Mana Sampei、Midori A. Arai、Masami Ishibashi

  DOI：10.1007/s11418-018-1198-6

  日期：2018.6

  pharmacological effects, including anti-tumor and antioxidative activities. Here, we describe the total synthesis of schizandriside (1), a compound we previously isolated from Saraca asoca by monitoring antioxidative activity using the 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. Starting from a tandem Michael-aldol reaction, the lignan skeleton was synthesized in 6 steps, including a cyclization

  木质素广泛分布于植物中，并表现出显着的药理作用，包括抗肿瘤和抗氧化活性。在这里，我们描述了schizandriside（1）的总合成，该化合物以前是通过使用1,1-二苯基-2-picylhydrazyl自由基清除试验监测抗氧化活性而从Saraca asoca分离得到的。从串联迈克尔-醛醇缩合反应开始，木脂素骨架是通过6个步骤合成的，包括环化步骤。为了确定1的立体化学，我们从乙醇17合成了天然产物（±）-异lariciresinol（18）。光谱数据的比较显示出良好的一致性。使用四种不同的糖基供体研究糖基化。只有使用三氟甲磺酸银和1,1,3,3-四甲基脲的Koenigs–Knorr条件才提供糖基化产物。使用反相高效液相色谱进行脱保护和纯化，得到了schizandriside（1）和其非对映异构体saracoside（2）。合成1，2和18显示出抗氧化活性与IC 50 分别= 34.4，28.8，53
• Pot-Economy Autooxidative Condensation of 2-Aryl-2-lithio-1,3-dithianes
  作者：João R. Vale、Tatu Rimpiläinen、Elina Sievänen、Kari Rissanen、Carlos A. M. Afonso、Nuno R. Candeias

  DOI：10.1021/acs.joc.7b02896

  日期：2018.2.16

  The autoxidative condensation of 2-aryl-2-lithio-1,3-dithianes is here reported. Treatment of 2-aryl-1,3-dithianes with n-BuLi in the absence of any electrophile leads to condensation of three molecules of 1,3-dithianes and formation of highly functionalized α-thioether ketones orthothioesters in 51-89% yields upon air exposure. The method was further expanded to benzaldehyde dithioacetals, affording corresponding orthothioesters and α-thioether ketones in 48-97% yields. The experimental results combined with density functional theory studies support a mechanism triggered by the autoxidation of 2-aryl-2-lithio-1,3-dithianes to yield a highly reactive thioester that undergoes condensation with two other molecules of 2-aryl-2-lithio-1,3-dithiane.
• Asymmetric synthesis, stereochemistry and rearrangement reactions of naturally occurring 7′-hydroxylignano-9,9′-lactones
  作者：Barbara Raffaelli、Kristiina Wähälä、Tapio Hase

  DOI：10.1039/b513303c

  日期：——

  The asymmetric synthesis of a series of (7'S,8R,8'R)-7'-hydroxylignano-9,9'-lactones is presented, among them the mammalian lignan (7'S)-hydroxyenterolactone and (7'S)-parabenzlactone, allowing the stereochemistry of natural occurring (-)-parabenzlactone to be re-assigned. A hydroxylactone rearrangement and its possible mechanisms are discussed. Finally a brief survey of the current naming and numbering

  提出了一系列（7'S，8R，8'R）-7'-hydroxylignano-9,9'-内酯的不对称合成，其中包括哺乳动物的木脂素（7'S）-羟基对映体内酯和（7'S）-对羟基苯甲酸酯。天然存在的（-）-对羟基苯甲酸酯的立体化学有待重新分配。羟基内酯重排及其可能的机制进行了讨论。最后，简要介绍了7'-羟基木质素-9,9'-内酯的当前命名和编号变体，并提出了统一术语的建议。