6-(tert-butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-cyclohex-2-enone | 863997-71-1

• 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: 6-(tert-butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-cyclohex-2-enone
• 英文别名: (4S,6S)-6-(tert-butyldirnethylsilyloxy)-4-(4-rnethoxybenzyloxy)cyclohex-2-enone；(4S,6S)-6-((tert-Butyldimethylsilyl)oxy)-4-((4-methoxybenzyl)oxy)cyclohex-2-en-1-one；(4S,6S)-6-[tert-butyl(dimethyl)silyl]oxy-4-[(4-methoxyphenyl)methoxy]cyclohex-2-en-1-one
• CAS: 863997-71-1
• 化学式: C₂₀H₃₀O₄Si
• 分子量: 362.541
• InChiKey: OKEZAAJYJFOJPF-MJGOQNOKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  6-(tert-butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-cyclohex-2-enone 在 四丁基氟化铵 、 溶剂黄146 、 偶氮二甲酸二乙酯 、 4-(二甲氨基)三苯基膦 作用下， 以 四氢呋喃 、 甲苯 、 苯 为溶剂， 反应 47.5h， 生成 (diethoxy-phosphoryl)-acetic acid 5-(4-methoxy-benzyloxy)-2-oxo-cyclohex-3-enyl ester
  参考文献：
  名称：

  Fluorescence study on the nyctinasty of Phyllanthus urinaria L. using novel fluorescence-labeled probe compounds

  摘要：

  We report the synthesis of fluorescence-labeled probes based on phyllanthurinolactone 1, which is a leaf-closing substance of Phyllanthus urinaria L. The fluorescence study using biologically active probe 2 and inactive probes (epi-2 and 31) revealed that the target cell for 1 is a motor cell and suggested that some receptors, which recognize the aglycon of I exist on the plasma membrane of the motor cell, as with leaf-opening substances. Moreover, binding of probe 2 was specific to the plant motor cell contained in the plants belonging to the genus Phyllanthus. These results showed that the binding of probe 2 with a motor cell is specific to the plant genus and suggested that the genus-specific receptor for the leaf-closing substance would be involved in nyctinasty. (c) 2006 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2006.05.022
• 作为产物：
  描述：

  1,4-环己二烯 在 咪唑 、 四氧化锇 、 正丁基锂 、 2,2,6,6-四甲基哌啶氧化物 、 四丁基氟化铵 、 trityl tetrafluoroborate 、 碳酸氢钠 、 对甲苯磺酸 、 N-甲基吗啉氧化物 、 间氯过氧苯甲酸 、 (1R,2S)-N-methyl-1-phenyl-2-(1-pyrrolidinyl)-1-propanamine 作用下， 以 四氢呋喃 、 正己烷 、 二氯甲烷 、 环己烷 、 水 、 丙酮 为溶剂， 反应 162.25h， 生成 6-(tert-butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-cyclohex-2-enone
  参考文献：
  名称：

  Trioxacarcin DC‐45‐A2的全合成

  摘要：

  描述了三氧杂色胺DC‐45‐A2（1）的对映选择性全合成，其特征是新颖的路易斯酸诱导的环氧酮6级联重排，以锻造该分子的多加氧2,7-二氧杂双环[2.2.1]庚烷核。

  DOI：

  10.1002/anie.201410369
• 作为试剂：
  描述：

  叔丁基二甲基氯硅烷 、 、 6-hydroxy-4-(4-methoxy-benzyloxy)-cyclohex-2-enone 、 咪唑 在 水 、 氯化钠 、 乙酸乙酯 、 Sodium sulfate-III 、 6-(tert-butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-cyclohex-2-enone 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.75h， 以to provide 29 mg of the product, (4S,6S)-6-(tert-butyldimethylsilyloxy)-4-(4-methoxybenzyloxy)cyclohex-2-enone的产率得到6-(tert-butyl-dimethyl-silanyloxy)-4-(4-methoxy-benzyloxy)-cyclohex-2-enone
  参考文献：
  名称：

  TRIOXACARCINS AND USES THEREOF

  摘要：

  本发明涉及式(I)的三氧卡西林化合物或其药学上可接受的形式；其中R1、R2、R3、R4、R5、R6、R7、R8和R9如本文所定义。本发明还提供制备这种化合物和中间体的过程；包含这种化合物的药物组合物；以及使用和治疗的方法。

  公开号：

  US20130150314A1

文献信息

• Streamlined Total Synthesis of Trioxacarcins and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues Thereof. Discovery of Simpler Designed and Potent Trioxacarcin Analogues
  作者：K. C. Nicolaou、Pengxi Chen、Shugao Zhu、Quan Cai、Rohan D. Erande、Ruofan Li、Hongbao Sun、Kiran Kumar Pulukuri、Stephan Rigol、Monette Aujay、Joseph Sandoval、Julia Gavrilyuk

  DOI：10.1021/jacs.7b08820

  日期：2017.11.1

  A streamlined total synthesis of the naturally occurring antitumor agents trioxacarcins is described, along with its application to the construction of a series of designed analogues of these complex natural products. Biological evaluation of the synthesized compounds revealed a number of highly potent, and yet structurally simpler, compounds that are effective against certain cancer cell lines, including

  描述了天然存在的抗肿瘤剂三氧嘧啶的流线型全合成，以及其在构建这些复杂天然产物的一系列设计类似物中的应用。对合成化合物的生物学评估揭示了许多高效但结构更简单的化合物，它们对某些癌细胞系（包括耐药细胞系）有效。还描述了从简单的酮前体和苯基硒基氯一步合成蒽醌和氯蒽醌的新方法。所报告的工作以新的化学和级联反应为特色，在癌症治疗中具有潜在的应用，包括在抗体-药物偶联物中的靶向方法。
• [EN] TRIOXACARCIN ANALOGS AND DIMERS AS POTENT ANTICANCER AGENTS<br/>[FR] ANALOGUES ET DIMÈRES DE TRIOXACARCINE EN TANT QU'AGENTS ANTICANCÉREUX PUISSANTS
  申请人：UNIV RICE WILLIAM M

  公开号：WO2019036537A1

  公开（公告）日：2019-02-21

  In one aspect, the present disclosure provides trioxacarcin analogs of the formula: wherein the variables are as defined herein. In another aspect, the present disclosure also provides methods of preparing the compounds disclosed herein as well as dimers of the compounds described herein. In another aspect, the present disclosure also provides pharmaceutical compositions and methods of use of the compounds disclosed herein. Additionally, drug conjugates with cell targeting moieties of the compounds are also provided.

  在一个方面，本公开提供了以下式的三氧环霉素类似物：其中变量如本文所定义。在另一个方面，本公开还提供了制备本文所披露的化合物以及本文所描述的二聚体的方法。在另一个方面，本公开还提供了药物组合物和使用本文所披露的化合物的方法。此外，还提供了具有化合物的细胞靶向基团的药物结合物。
• [EN] TRIOXACARCINS AND USES THEREOF<br/>[FR] TRIOXACARCINES ET UTILISATIONS DE CELLES-CI
  申请人：HARVARD COLLEGE

  公开号：WO2011119549A1

  公开（公告）日：2011-09-29

  The present invention relates to trioxacarcin compounds of the formula: (I) or pharmaceutically acceptable forms thereof; wherein R1, R2, R3, R4, R5, R6, R7, R8, and R9 are as defined herein. The present invention also provides processes for preparing such compounds and intermediates thereto; pharmaceutical compositions comprising such compounds; and methods of use and treatment.

  本发明涉及以下式的三氧卡尔辛化合物（I）或其药用可接受形式；其中R1、R2、R3、R4、R5、R6、R7、R8和R9如本文所定义。本发明还提供了制备这种化合物及其中间体的方法；包括这种化合物的药物组合物；以及使用和治疗方法。
• A multiply convergent platform for the synthesis of trioxacarcins
  作者：Jakub Švenda、Nicholas Hill、Andrew G. Myers

  DOI：10.1073/pnas.1015257108

  日期：2011.4.26

  Many first-line cancer drugs are natural products or are derived from them by chemical modification. The trioxacarcins are an emerging class of molecules of microbial origin with potent antiproliferative effects, which may derive from their ability to covalently modify duplex DNA. All trioxacarcins appear to be derivatives of a nonglycosylated natural product known as DC-45-A2. To explore the potential of the trioxacarcins for the development of small-molecule drugs and probes, we have designed a synthetic strategy toward the trioxacarcin scaffold that enables access to both the natural trioxacarcins and nonnatural structural variants. Here, we report a synthetic route to DC-45-A2 from a differentially protected precursor, which in turn is assembled in just six steps from three components of similar structural complexity. The brevity of the sequence arises from strict adherence to a plan in which strategic bond-pair constructions are staged at or near the end of the synthetic route.

  许多一线癌症药物是天然产物或经过化学修饰得到的。三氧环菌素是一类新兴的微生物来源分子，具有强大的抗增殖作用，可能源于它们能够共价修饰双链DNA的能力。所有的三氧环菌素似乎都是一种非糖基化的天然产物DC-45-A2的衍生物。为了探索三氧环菌素作为小分子药物和探针的潜力，我们设计了一种合成策略，以便访问天然的三氧环菌素和非自然的结构变体。在这里，我们报道了从不同保护的前体合成DC-45-A2的方法，该前体仅需从三个结构复杂度相似的组分中经过六个步骤组装而成。这一序列的简洁性源于对计划的严格遵守，其中战略性的键对构造在合成路径的末端或附近进行分阶段。
• Component-based syntheses of trioxacarcin A, DC-45-A1 and structural analogues
  作者：Thomas Magauer、Daniel J. Smaltz、Andrew G. Myers

  DOI：10.1038/nchem.1746

  日期：2013.10

  The trioxacarcins are polyoxygenated, structurally complex natural products that potently inhibit the growth of cultured human cancer cells. Here we describe syntheses of trioxacarcin A, DC-45-A1 and structural analogues by late-stage stereoselective glycosylation reactions of fully functionalized, differentially protected aglycon substrates. Key issues addressed in this work include the identification of an appropriate means to activate and protect each of the two 2-deoxysugar components, trioxacarcinose A and trioxacarcinose B, as well as a viable sequencing of the glycosidic couplings. The convergent, component-based sequence we present allows for rapid construction of structurally diverse, synthetic analogues that would be inaccessible by any other means, in amounts required to support biological evaluation. Analogues that arise from the modification of four of five modular components are assembled in 11 steps or fewer. The majority of these are found to be active in antiproliferative assays using cultured human cancer cells. The trioxacarcins are polyoxygenated natural products that potently inhibit the growth of cultured human cancer cells. Here, the syntheses of trioxacarcin A, DC-45-A1 and structural analogues are described — the majority of which were found to be active in antiproliferative assays. A convergent, component-based route comprising sequential stereoselective glycosylation reactions allows assembly of these analogues in 11 steps or fewer.

  三氧杂蒽是一种多氧、结构复杂的天然产物，能有效抑制培养的人类癌细胞的生长。在这里，我们描述了通过对完全功能化、不同保护的苷元底物进行后期立体选择性糖基化反应，合成三氧杂蒽 A、DC-45-A1 和结构类似物的过程。这项工作所解决的关键问题包括确定适当的方法来激活和保护两种 2-脱氧糖成分（三氧卡果糖 A 和三氧卡果糖 B），以及对糖苷键合进行可行的测序。我们提出的基于成分的聚合序列可以快速构建结构多样的合成类似物，而这些类似物的数量是任何其他方法都无法达到的，以支持生物学评估。通过对五个模块化组件中的四个组件进行修改，只需 11 个或更少的步骤就能组装出类似物。在使用培养的人类癌细胞进行的抗增殖试验中，发现其中大多数都具有活性。三氧杂蒽是一种多氧天然产物，能有效抑制培养的人类癌细胞的生长。本文介绍了三氧杂蒽 A、DC-45-A1 和结构类似物的合成过程。这些类似物的合成只需11个或更少的步骤。