Terminal Alkylation of Linear Polyamines.
Terminal Alkylation of Linear Polyamines.
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线性多胺的末端烷基化。
DOI：
10.1002/chin.199636083
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发表时间：
1996
期刊：
影响因子：
--
通讯作者：
S. V. van Arman
中科院分区：
文献类型：
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作者：
J. Sclafani;Marianna Maranto;Thomas Sisk;S. V. van Arman
在过去的几年里，线性和大环多胺在文献中已经是一个普遍的特征。它们已经被广泛研究了它们与几种非共价缔合客体的结合特性。1精胺及其前体（存在于所有细胞中2）在生物学中的作用已被广泛研究。它们可以影响DNA形态3，并可能参与蛋白质合成的各个步骤。在脑化学中，它们被证明参与N-甲基-D-天冬氨酸受体的变构调节。4这些功能中的许多已经表明基于这些和其他线性多胺及其与其他部分的合成缀合物的化合物的医学应用（用于NMDA受体，5系统性红斑狼疮，6和心脏病7）。此外，最近的生物合成策略已针对多胺的生物合成途径。因此，已经设计了几种策略来通过保护/脱保护方案选择性地修饰线性多胺。8a，9还原胺化已被证明是用保护的内胺烷基化多胺的末端氮的有用方法。10 Martell 11详细阐述了Lehn和Pascard的工作，指出保护步骤可能不是必要的。我们感兴趣的是双末端取代的线性多胺作为金属离子的荧光探针的潜在用途。金属离子通过这样的物质的适当络合可以诱导其中分子内激基缔合物形成提供荧光信号的构象。我们在这里报告的一般使用一个简单的还原胺化序列的烷基化末端胺在线性多胺。未观察到来自内部（仲）胺位点处的反应的产物。我们试图通过在氯甲基芳烃上进行简单的取代反应或在甲苯磺酸酯保护的多胺上进行取代来合成这些化合物，但没有成功。
Polyamines, both linear and macrocyclic, have been a pervasive feature in the literature over the past several years. They have been studied extensively for their binding properties with several varieties of non-covalently associated guests. 1 Spermine and its precursors (present in all cells2) have been widely examined for their roles in biology. They can influence DNA morphology3 and are likely to be involved in various steps of protein synthesis. 2 They have been shown to participate in allosteric modulation of the N-methyl-D-aspartate receptor in brain chemistry. 4 Many of these functions have suggested medical applications for compounds based on these and other linear polyamines and their synthetic conjugates with other moieties (for NMDA receptor, 5 systemic lupus erythematosus, 6 and heart disease7). In addition, recent antineoplastic strategies have been targeted toward polyamine biosynthetic pathways. 8 Accordingly, several strategies have been devised to selectively modify linear polyamines by protection/deprotection schemes. 8a, 9 Reductive amination has been shown to be a useful method for alkylating the terminal nitrogens of polyamines with protected internal amines. 10 Martell11 elaborated on the work of Lehn and Pascard indicating that the protection step may not be necessary. We are interested in the potential use of bis-terminally substituted linear polyamines as fluorescence probes for metal ions. Proper complexation of a metal ion by such a species may induce a conformation in which intramolecular excimer formation provides a fluorescent signal. We report here the general use of a simple reductive amination sequence for the alkylation of terminal amines in linear polyamines. No products from reaction at internal (secondary) amine sites are observed. Our efforts to synthesize these compounds using a simple substitution reaction on chloromethylarenes, 12 or by substitution on tosylate protected polyamines, were unsuccessful.