4-methoxy-5-[(5-ethyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole | 289058-26-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 4-methoxy-5-[(5-ethyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole
• 英文别名: marineosin A；2-[(5-ethyl-1H-pyrrol-2-yl)methylidene]-3-methoxy-5-(1H-pyrrol-2-yl)pyrrole
• CAS: 289058-26-0
• 化学式: C₁₆H₁₇N₃O
• 分子量: 267.33
• InChiKey: ANSLXJCHRCGPSG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  20
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  53.2
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  乙酸酐 、 4-methoxy-5-[(5-ethyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole 在 三氯化铝 作用下， 以 二氯甲烷 为溶剂， 反应 3.0h， 以55%的产率得到5'-acetyl-4-methoxy-5-[(5-ethyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole
  参考文献：
  名称：

  A环对prodigiosins的氧化还原和核酸酶特性的影响：联吡咯部分在氧化DNA切割中的重要性。

  摘要：

  Prodigiosin（Prod，1）是一类聚吡咯天然产物的母体，具有良好的免疫抑制和细胞毒性活性。它们可以通过还原活化Cu（II）促进铜促进的氧化双链（ds）DNA裂解。这是由富电子的Prod分子的氧化触发的，并可能为pro虫的细胞毒性提供基础。为了了解这种活性，我们制备了几种具有各种A环系统的Prod类似物，以检查它们在乙腈（MeCN）中的电化学性质，以此为建立铜促进核酸酶活性中的结构反应性关系奠定基础。完整的联吡咯（BP）生色团对于铜介导的Prods核酸酶特性至关重要。事实上，显示了简单的BP系统可促进氧化单链（ss）DNA裂解。用替代的芳烃（苯基，呋喃-2-基或噻吩-2-基）取代Prod A-吡咯环可抑制DNA链断裂，并提高Prod的半峰氧化电位（E（p / 2））游离碱[E（p / 2）= 0.44 V对MeCN中的饱和甘汞电极（SCE）]大约。200毫伏。通过在A-吡咯环的5'

  DOI：

  10.1021/tx025508p
• 作为产物：
  描述：

  4-methoxy-5-(5-ethyl-1H-pyrrol-2-ylmethylidene)-1,5-dihydropyrrol-2-one 在 potassium carbonate 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 25.0h， 生成 4-methoxy-5-[(5-ethyl-2H-pyrrol-2-ylidene)methyl]-2,2'-bi-1H-pyrrole
  参考文献：
  名称：

  Influence of the A-Ring on the Proton Affinity and Anticancer Properties of the Prodigiosins

  摘要：

  Prodigiosin (Prod, 1) is the parent member of a class of polypyrrole natural products that exhibit promising immunosuppressive and anticancer activities. They are known to act as H+/ Cl- symporters possibly through electrostatic binding to Cl- that facilitates proton-coupled transmembrane transport of halides. This activity has been ascribed to their promotion of apoptosis by acidification of the intracellular pH (pHi). Since the protonated pyrromethene chromophore of Prod (1) is expected to play a critical role in pHi regulation, and the A-pyrrole ring is known to be important for anticancer activity, we prepared several Prod analogues with various A-ring systems to determine their proton affinity in 1: 1 (v/v) acetonitrile (MeCN)/ H2O and anticancer properties against HL-60 cancer cells. Our studies show that the A-ring strongly influences the proton affinity of the pyrromethene entity. Replacement of the C-2 methoxy group in 2,4-dimethoxy-pyrromethene 3 (apparent pK(a) = 4.95) with the A-pyrrole ring to generate the Prod analogue 5 raised the apparent pK(a) to 7.54 (increase by 2.59 pK units) and caused a 76 nm red shift in the UV-vis absorbance of the protonated species (AH(+)). The A-pyrrole NH atom plays an important role in stabilization of AH(+), as its replacement with 0 or S atoms decreases the apparent pK(a) by 0.79 and 1.07 pK units, respectively. A 4-substituted phenyl series of Prod analogues 8-14 exhibited a linear correlation with the Hammett sigma(p) values. Within the phenyl series, two Prod analogues were found to inhibit colony formation of HL-60 cancer cells, although the inhibition did not correlate with the proton affinity of the pyrromethene entity. The implications of these findings with regard to the anticancer activities of the prodigiosins are discussed.

  DOI：

  10.1021/tx025507x