N¹,N⁴-Methylenespermidine | 73453-98-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N¹,N⁴-Methylenespermidine
• 英文别名: 1-(4-aminobutyl)-1,2,3,4,5,6-hexahydropyrimidine；1-(4-aminobutyl)hexahydropyrimidine；1(2H)-Pyrimidinebutanamine, tetrahydro-；4-(1,3-diazinan-1-yl)butan-1-amine
• CAS: 73453-98-2
• 化学式: C₈H₁₉N₃
• 分子量: 157.259
• InChiKey: DZIUYPHPZLFPIH-UHFFFAOYSA-N

物化性质

• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  11
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  41.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N¹,N⁴-Methylenespermidine 在 吡啶 、 丙二酸 、 三乙胺 作用下， 以 四氢呋喃 、 乙醇 为溶剂， 反应 12.0h， 生成 N¹,N⁸-bis(benzyloxycarbonylglycyl)-spermidine
  参考文献：
  名称：

  Henderson, Graeme B.; Glushka, John; Cowburn, David, Journal of the Chemical Society. Perkin transactions I, 1990, # 4, p. 911 - 914

  摘要：

  DOI：
• 作为产物：
  描述：

  聚合甲醛 、 亚精胺 以 水 为溶剂， 反应 1.0h， 以91%的产率得到N¹,N⁴-Methylenespermidine
  参考文献：
  名称：

  Macrocyclic polyamine lactam synthesis by diphenyl ether closure of 23-, 24- and 28-membered rings

  摘要：

  新型的23、24和28成员的环状聚胺酰胺（肉桂酰胺）通过二苯醚的闭合反应制备而成；功能化的精胺和精胺的共轭物经过分子内芳香族亲核取代反应，生成了硝基取代的卡达比辛类（24成员聚胺内酰胺）生物碱的类似物。

  DOI：

  10.1039/a806688d

文献信息

• The synthesis of novel polyamine–nitroimidazole conjugates designed to probe the structural specificities of the polyamine uptake system in A549 lung carcinoma cells
  作者：Adam Q. Siddiqui、Louise Merson-Davies、Paul M. Cullis

  DOI：10.1039/a903293b

  日期：——

  Synthetic routes were developed to synthesise an N 4-mono-derivatised spermidine–nitroimidazole conjugate and two novel structural isomers (N 1- and N 8-spermidine–nitroimidazole conjugates). A synthetic method was developed to synthesise an N 1,N 7-bis-derivatised norspermidine–nitroimidazole conjugate and further applied to the synthesis of an N 1,N 8-bis-derivatised spermidine–nitroimidazole conjugate. The compounds were examined for their ability to serve as substrates for the polyamine uptake system in A549 lung carcinoma cells, by measuring their inhibition of [14C]spermidine uptake. Marked differences were observed between the nitroimidazole–polyamine conjugates. For maximum recognition as a substrate by the polyamine transport system, the aminobutyl unit of spermidine should remain underivatised. The preferred site(s) for spermidine amino derivatisation was in the order: N 1 > N 8 ≈ N 1, N 8 > N 4.

  开发了合成路线以合成N4-单衍生化spermidine-硝基咪唑偶联物以及两种新型结构异构体（N1-和N8-spermidine-硝基咪唑偶联物）。开发了一种合成方法以合成N1，N7-双衍生化norspermidine-硝基咪唑偶联物，并进一步应用于合成N1，N8-双衍生化spermidine-硝基咪唑偶联物。通过测量它们对[14C]精胺摄取的抑制作用，考察了这些化合物作为A549肺癌细胞中多胺摄取系统底物的能力。观察到硝基咪唑-多胺偶联物之间显著的差异。为了最大限度地被多胺转运系统识别为底物，精胺的氨基丁基单元应保持非衍生化状态。精胺氨基衍生化的优选位点依次为：N1 > N8 ≈ N1，N8 > N4。
• N4-Benzoylspermidine fromOncinotis tenuiloba: Analytical differentiation of the three isomericN-benzoylspermidines
  作者：Martin K.-H. Doll、Armin Guggisberg、Manfred Hesse

  DOI：10.1002/hlca.19940770505

  日期：1994.8.10

  During the examination of extracts from Oncinotis tenuiloba STAPF a new polyamine, N4-benzoylsperimidine (8), was isolated. For unambiguous structure elucidation, it was transformed into the diacetyl derivative 13, and the three possible N-benzoyl-substituted isomers of spermidine 5, 8, and 11 together with their peracetylated derivatives 12–14, respectively, were synthesized and identified.

  在检查来自Oncinotis tenuiloba STAPF的提取物的过程中，分离了一种新的多胺N 4-苯甲酰亚精胺（8）。对于明确的结构解析，将其转化为二乙酰衍生物13，和三个可能Ñ亚精胺-苯甲酰基-取代的异构体5,8和11与它们的全乙酰化的衍生物一起12-14，分别合成并鉴定。
• Macrocyclic Polyamines Deplete Cellular ATP Levels and Inhibit Cell Growth in Human Prostate Cancer Cells
  作者：Benjamin Frydman、Subhra Bhattacharya、Aparajita Sarkar、Konstantin Drandarov、Sergiy Chesnov、Armin Guggisberg、Kasim Popaj、Sergey Sergeyev、Aysil Yurdakul、Manfred Hesse、Hirak S. Basu、Laurence J. Marton

  DOI：10.1021/jm030437s

  日期：2004.2.1

  budmunchamine family of alkaloids, were prepared by total synthesis. They were the [17]-N(4) macrocycle 1, the [16]-N(4) macrocycle 20, the [18]-N(4) macrocycle 13, the [20]-N(5) macrocycle 8, and the [13]-N(3) macrocycle 17. Each one of them hydrolyzed ATP in vitro with release of P(i); the largest ring macrocycle 8 was the most efficient catalyst, while the smallest ring macrocycle 17 was the least

  在实体瘤中，当O（2）的分压降至10 mmHg以下时，由于Warburg效应，ATP水平迅速降低。已知某些大环多胺可催化ATP的化学水解并释放出无机磷酸盐。由于与正常细胞相比，肿瘤细胞的ATP水平降低，因此我们试图用大环多胺消耗细胞的ATP，以抑制肿瘤细胞的增殖。通过全合成制备了五种与生物碱的花香胺家族有关的大环多胺。它们是[17] -N（4）宏周期1，[16] -N（4）宏周期20，[18] -N（4）宏周期13，[20] -N（5）宏周期8，和[13] -N（3）大环化合物17。它们每个都在体外水解ATP，并释放P（i）。最大的环状大环8是最有效的催化剂，而最小的环形大环17效率最低（在这些运行中释放的P（i）约为40-100 microM）。线性多胺精胺对ATP没有水解作用。当通过MTT测定针对两种人类前列腺细胞系DuPro和PC-3进行评估时，发现大环具有细胞毒性，其ID（50）值介于0
• Synthetic Analogues of Naturally Occurring Spider Toxins: Synthesis of 2-(Hydroxyphenyl)propanamides of Spermidine and Spermine
  作者：Kasim Popaj、Armin Guggisberg、Manfred Hesse

  DOI：10.1002/1522-2675(20010418)84:4<797::aid-hlca797>3.0.co;2-2

  日期：2001.4.18

  structure-activity relationships of spider toxins, six model compounds, namely the spermidine derivatives 6, 8, and 16 as well as the spermine derivatives 24, 27, and 32 were synthesized. The synthesis proceeds through stepwise construction of the polyamine backbone, including protection and deprotection of the amino functions. The differentiation of the derivatives by analytical and spectroscopic methods is discussed

  在对蜘蛛毒素构效关系的研究中，合成了六种模型化合物，即亚精胺衍生物 6、8 和 16 以及精胺衍生物 24、27 和 32。合成通过逐步构建多胺骨架进行，包括氨基官能团的保护和去保护。讨论了通过分析和光谱方法对衍生物进行区分。
• Total synthesis of modified jstx toxins: reductive alkylation is a practical route to hexahydropyrimidine polyamine amides
  作者：Mark R. Ashton、Eduardo Moya、Ian S. Blagbrough

  DOI：10.1016/0040-4039(95)01995-t

  日期：1995.12

  Reductive alkylation is a practical route for a total synthesis of regioisomers of spider toxin JSTX-3, a polyamine amide which is a selective glutamate receptor antagonist and may have potential as a neuroprotective agent. The strategy is based upon a reductive alkylation step which enables one free araine to be generated regiospecifically in the new polyamine, or the regiospecific incorporation of

  还原烷基化是全部合成蜘蛛毒素JSTX-3的区域异构体的实用途径，JSTX-3是一种多胺酰胺，是一种选择性的谷氨酸受体拮抗剂，可能具有作为神经保护剂的潜力。该策略基于还原性烷基化步骤，该步骤能够在新的多胺中区域特异性地产生一个游离的阿拉伯氨酸，或者在构象上限制了多胺酰胺主链的六氢嘧啶部分的区域特异性结合。