2-(2,3-dihydro-1,4-benzodioxan-6-yl)-3-buten-2-ol | 203856-21-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: 2-(2,3-dihydro-1,4-benzodioxan-6-yl)-3-buten-2-ol
• 英文别名: 2-(2,3-Dihydro-1,4-benzodioxin-6-yl)but-3-en-2-ol
• CAS: 203856-21-7
• 化学式: C₁₂H₁₄O₃
• 分子量: 206.241
• InChiKey: VBSYKZANXQBWBQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  38.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-(2,3-dihydro-1,4-benzodioxan-6-yl)-3-buten-2-ol 在 正丁基锂 作用下， 以 四氢呋喃 、 甲醇 、 正己烷 为溶剂， 反应 20.5h， 生成 ethyl (2E,4E,6E)-7-(2,3-dihydro-1,4-benzodioxin-6-yl)-3-methylocta-2,4,6-trienoate
  参考文献：
  名称：

  Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors

  摘要：

  A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu / nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RAR alpha, RXR alpha, and RXR beta were similar in the two cell lines, while RAR beta expression was higher in SCC-2 over SCC-38, and RAR gamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.

  DOI：

  10.1021/jm990292i
• 作为产物：
  描述：

  6-乙酰基-1,4-苯并二氧杂环 、 乙烯基溴化镁 以 四氢呋喃 为溶剂， 生成 2-(2,3-dihydro-1,4-benzodioxan-6-yl)-3-buten-2-ol
  参考文献：
  名称：

  镍催化区域选择性和对映选择性同烯丙基偶联：具有四元立构中心的手性支化 1,5-二烯的合成及机理分析

  摘要：

  在镍催化下，烯丙基碳酸酯的还原交叉亲电子偶联可得到独特的 1,5-二烯，该二烯具有在高化学、区域、非对映和对映体控制下的季立体中心。机理研究与基于 Ni(0)/Ni(II) 电对的催化循环非常吻合，二价 Zn 在提高整体动力学和选择性方面发挥着至关重要的作用，同时有利于关键双金属 C−C 键的形成。

  DOI：

  10.1002/anie.202314865

文献信息

• Heteroarotinoids Inhibit Head and Neck Cancer Cell Lines in Vitro and in Vivo Through Both RAR and RXR Retinoic Acid Receptors
  作者：David Zacheis、Arindam Dhar、Shennan Lu、Matora M. Madler、Jozef Klucik、Chad W. Brown、Shengquan Liu、Francis Clement、Shankar Subramanian、G. Mahika Weerasekare、K. Darrell Berlin、Michael A. Gold、John R. Houck,、Kenneth R. Fountain、Doris M. Benbrook

  DOI：10.1021/jm990292i

  日期：1999.10.1

  A class of less toxic retinoids, called heteroarotinoids, was evaluated for their molecular mechanism of growth inhibition of two head and neck squamous cell carcinoma (HNSCC) cell lines SCC-2 and SCC-38. A series of 14 heteroarotinoids were screened for growth inhibition activity in vitro. The two most active compounds, one that contained an oxygen heteroatom (6) and the other a sulfur heteroatom (16), were evaluated in a xenograph model of tumor establishment in nude mice. Five days after subcutaneous injection of 10(7) SCC-38 cells, groups of 5 nu / nu mice were gavaged daily (5 days/week for 4 weeks) with 20 mg/kg/day of all-trans-retinoic acid (t-RA, 1), 10 mg/kg/day of 6, 10 mg/kg/day of 16, or sesame oil. After a few days, the dose of t-RA (1) was decreased to 10 mg/kg/day to alleviate the side effects of eczema and bone fracture. No significant toxic effects were observed in the heteroarotinoid groups. All three retinoids caused a statistically significant reduction in tumor size as determined by the Student t-test (P < 0.05). Complete tumor regression was noted in 3 of 5 mice treated with t-RA (1), 4 of 5 mice treated with 16, 1 of 5 mice treated with 6, and 1 of 5 mice treated with sesame oil. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to determine that the expression levels of RAR alpha, RXR alpha, and RXR beta were similar in the two cell lines, while RAR beta expression was higher in SCC-2 over SCC-38, and RAR gamma expression was higher in SCC-38 over SCC-2. Receptor cotransfection assays in CV-1 cells demonstrated that 16 was a potent activator of both RAR and RXR receptors, while 6 was selective for the RXR receptors. Transient cotransfection assays in CV-1 cells using an AP-1 responsive reporter plasmid demonstrated that t-RA (1), 6, and 16 each inhibited AP-1-driven transcription in this cell line. In conclusion, the growth inhibition activity of the RXR-selective 6 and the more potent growth inhibition activity of the RAR/RXR pan-agonist 16 implicate both RARs and RXRs in the molecular mechanism of retinoid growth inhibition. Moreover, the chemoprevention activity and the lack of toxicity of heteroarotinoids demonstrate their clinical potential in head and neck cancer chemoprevention.
• Ni‐Catalyzed Regio‐ and Enantioselective Homoallylic Coupling: Synthesis of Chiral Branched 1,5‐Dienes Featuring a Quaternary Stereogenic Center and Mechanistic Analysis
  作者：Debasish Ghorai、Aleria Garcia‐Roca、Balázs L. Tóth、Jordi Benet‐Buchholz、Arjan W. Kleij

  DOI：10.1002/anie.202314865

  日期：2023.12.11

  A reductive cross-electrophile coupling of allylic carbonates under Ni-catalysis provides access to unique 1,5-dienes featuring a quaternary stereogenic center under high chemo-, regio-, diastereo- and enantio-control. Mechanistic studies align well with a catalytic cycle based on a Ni(0)/Ni(II) couple with a crucial role for divalent Zn boosting the overall kinetics and selectivity while favoring

  在镍催化下，烯丙基碳酸酯的还原交叉亲电子偶联可得到独特的 1,5-二烯，该二烯具有在高化学、区域、非对映和对映体控制下的季立体中心。机理研究与基于 Ni(0)/Ni(II) 电对的催化循环非常吻合，二价 Zn 在提高整体动力学和选择性方面发挥着至关重要的作用，同时有利于关键双金属 C−C 键的形成。