3-((4-chlorophenyl)carbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid | 87126-55-4

• 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-((4-chlorophenyl)carbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid
• 英文别名: exo-7-oxa-bicyclo[2,2,1]-heptane-3-(p-Cl-C6H3)amide-3-carboxylic acid；(1R,2S,3R,4S)-3-[(4-chlorophenyl)carbamoyl]-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid
• CAS: 87126-55-4
• 化学式: C₁₄H₁₄ClNO₄
• 分子量: 295.722
• InChiKey: PQYZQPSVUBGXDH-WHOHXGKFSA-N

物化性质

• 沸点：
  571.4±50.0 °C(Predicted)
• 密度：
  1.485±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  四苯基溴化锑 、 3-((4-chlorophenyl)carbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid 在 三乙胺 作用下， 以 甲苯 为溶剂， 以80%的产率得到exo-7-oxa-bicyclo[2,2,1]-heptane-3-(p-Cl-C6H3)amide-3-carboxylic acid, mono(tetraphenylantimony) derivative
  参考文献：
  名称：

  SYNTHESIS, SPECTROSCOPIC CHARACTERIZATION, AND IN VITRO ANTITUMOR ACTIVITY OF TETRAPHENYLANTIMONY DERIVATIVES OF ANALOGUES OF DEMETHYLCANTHARIDIN AND DEMETHYLDEHYDROGEN-CANTHARIDIN

  摘要：

  A series of novel tetraphenylantimony(V) derivatives of the analogues of demethylcantharidin and demethyl-dehydrogencantharidin, exo-7-oxa-bicyclo[2,2,1]-heptane-3-arylamide-2-carboxylic acid and exo-7-oxa-bicyclo[2,2,1]-heptene-3-arylamide-2-carboxylic acid, of the general formulas Ph4SbO2CCHCH=CHCH(O)CHCO2SbPh4, Ph4SbO2CCHCHCH2CH2CH(O)CHCO2SbPh4, Ph4SbO2- CCHCHCH=CHCH(O)CHCONHAr, and Ph4SbO2- CCHCHCH2CH2CH(O)-CHCONHr [Ar=p-ClC6H4, p-F-m-(ClCH3)-H-6 and m-Me-C6H4] have been synthesized and characterized by elemental analyses, IR, H-1 NMR and mass spectroscopy. Preliminary antitumor activity tests show that these compounds have significant antitumor activity in i,itro against five human neoplastic cell lines.

  DOI：

  10.1081/sim-120003797
• 作为产物：
  描述：

  对氯苯胺 、 norcantharidin 在 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 14.0h， 以56%的产率得到3-((4-chlorophenyl)carbamoyl)-7-oxabicyclo[2.2.1]heptane-2-carboxylic acid
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents

  摘要：

  基于天然斑蝥素结构，将不同的芳香胺与去甲斑蝥素骨架相连接，合成了36个化合物。并通过熔点测定、1H-NMR、13C-NMR以及HRMS-ESI等方法证实其结构。以菌丝生长速率法对其进行了抑菌活性测试，结果发现：在36个衍生物中，有7个衍生物的抑菌活性高于去甲斑蝥素，有7个衍生物的抑菌活性高于斑蝥素，有3个衍生物的抑菌活性高于多菌灵。尤其是化合物3-(3'-氯苯基)氨基甲酰去甲斑蝥酸二甲酯(II-8)对褐腐菌和菌核菌的抑制活性最高，其IC50值分别为0.88和0.97 μg/mL。通过对化合物的结构活性关系研究发现，对于抑菌谱的提升，苯环至关重要(3-苯基氨基甲酰去甲斑蝥酸二甲酯(II-1)相对于去甲斑蝥素和斑蝥素)；在苯环上的三个取代位点中，即C-2'、C-3'和C-4'位点，在C-3'位点连接卤素原子会最大程度地增加化合物抑菌活性；具有强吸电子基或者供电子基的取代基均导致化合物的抑菌活性较差；相对于氟、溴、碘，氯在苯环的C-3'位点对化合物抑菌活性促进最为显著。因此，化合物II-8为创制新的杀菌剂提供了一种新的先导结构。

  DOI：

  10.3390/molecules201219782

文献信息

• Synthesis and Biological Evaluation of Norcantharidin Derivatives Possessing an Aromatic Amine Moiety as Antifungal Agents
  作者：Yang Wang、Wenbo Sun、Shunqing Zha、Huan Wang、Yalin Zhang

  DOI：10.3390/molecules201219782

  日期：——

  Based on the structure of naturally produced cantharidin, different arylamine groups were linked to the norcantharidin scaffold to provide thirty six compounds. Their structures were confirmed by melting point, 1H-NMR, 13C-NMR and HRMS-ESI studies. These synthetic compounds were tested as fungistatic agents against eight phytopathogenic fungi using the mycelium growth rate method. Of these thirty six derivatives, seven displayed stronger antifungal activity than did norcantharidin, seven showed higher activity than did cantharidin and three exhibited more significant activity than that of thiabendazole. In particular, 3-(3′-chloro-phenyl)carbamoyl norcantharidate II-8 showed the most significant fungicidal activity against Sclerotinia fructigena and S. sclerotiorum, with IC50 values of 0.88 and 0.97 μg/mL, respectively. The preliminary structure-activity relationship data of these compounds revealed that: (1) the benzene ring is critical for the improvement of the spectrum of antifungal activity (3-phenylcarbamoyl norcantharidate II-1 vs norcantharidin and cantharidin); (2) among the three sites, including the C-2′, C-3′ and C-4′ positions of the phenyl ring, the presence of a halogen atom at the C-3′position of the benzene ring caused the most significant increase in antifungal activity; (3) compounds with strongly electron-drawing or electron-donating groups substitutions were found to have a poor antifungal activity; and (4) compared with fluorine, bromine and iodine, chlorine substituted at the C-3′ position of the benzene ring most greatly promoted fungistatic activity. Thus, compound II-8 has emerged as new lead structure for the development of new fungicides.

  基于天然斑蝥素结构，将不同的芳香胺与去甲斑蝥素骨架相连接，合成了36个化合物。并通过熔点测定、1H-NMR、13C-NMR以及HRMS-ESI等方法证实其结构。以菌丝生长速率法对其进行了抑菌活性测试，结果发现：在36个衍生物中，有7个衍生物的抑菌活性高于去甲斑蝥素，有7个衍生物的抑菌活性高于斑蝥素，有3个衍生物的抑菌活性高于多菌灵。尤其是化合物3-(3'-氯苯基)氨基甲酰去甲斑蝥酸二甲酯(II-8)对褐腐菌和菌核菌的抑制活性最高，其IC50值分别为0.88和0.97 μg/mL。通过对化合物的结构活性关系研究发现，对于抑菌谱的提升，苯环至关重要(3-苯基氨基甲酰去甲斑蝥酸二甲酯(II-1)相对于去甲斑蝥素和斑蝥素)；在苯环上的三个取代位点中，即C-2'、C-3'和C-4'位点，在C-3'位点连接卤素原子会最大程度地增加化合物抑菌活性；具有强吸电子基或者供电子基的取代基均导致化合物的抑菌活性较差；相对于氟、溴、碘，氯在苯环的C-3'位点对化合物抑菌活性促进最为显著。因此，化合物II-8为创制新的杀菌剂提供了一种新的先导结构。
• SYNTHESIS, SPECTROSCOPIC CHARACTERIZATION, AND IN VITRO ANTITUMOR ACTIVITY OF TETRAPHENYLANTIMONY DERIVATIVES OF ANALOGUES OF DEMETHYLCANTHARIDIN AND DEMETHYLDEHYDROGEN-CANTHARIDIN
  作者：Jin-Shan Li、Yong-Qiang Ma、Lin Yu、Jing-Rong Cui、Rui-Qing Wang

  DOI：10.1081/sim-120003797

  日期：2002.4.29

  A series of novel tetraphenylantimony(V) derivatives of the analogues of demethylcantharidin and demethyl-dehydrogencantharidin, exo-7-oxa-bicyclo[2,2,1]-heptane-3-arylamide-2-carboxylic acid and exo-7-oxa-bicyclo[2,2,1]-heptene-3-arylamide-2-carboxylic acid, of the general formulas Ph4SbO2CCHCH=CHCH(O)CHCO2SbPh4, Ph4SbO2CCHCHCH2CH2CH(O)CHCO2SbPh4, Ph4SbO2- CCHCHCH=CHCH(O)CHCONHAr, and Ph4SbO2- CCHCHCH2CH2CH(O)-CHCONHr [Ar=p-ClC6H4, p-F-m-(ClCH3)-H-6 and m-Me-C6H4] have been synthesized and characterized by elemental analyses, IR, H-1 NMR and mass spectroscopy. Preliminary antitumor activity tests show that these compounds have significant antitumor activity in i,itro against five human neoplastic cell lines.