Microwave-Assisted Desulfonylation of Polysulfonamides toward Polypropylenimine.
Microwave-Assisted Desulfonylation of Polysulfonamides toward Polypropylenimine.
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DOI：
10.1021/acsmacrolett.8b00180
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发表时间：
2018-05
影响因子：
5.8
通讯作者：
E. Rieger;Tassilo Gleede;A. Manhart;M. Lamla;F. Wurm
中科院分区：
文献类型：
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作者：
E. Rieger;Tassilo Gleede;A. Manhart;M. Lamla;F. Wurm
线性聚乙烯亚胺（L - PEI）一直是基因传递的金标准，通常由聚（2 - 噁唑啉）水解制备。最近，活性氮丙啶的阴离子聚合也被报道为制备线性且结构明确的多胺的一种潜在途径。然而，到目前为止只有磺酰胺活化的氮丙啶能进行活性阴离子聚合，并且其脱磺酰化的报道很少。这主要是由于磺酰胺的稳定性相对较高以及脱磺酰化过程中溶解性的剧烈变化。在此，我们研究了由对甲苯磺酰化或甲磺酰化丙烯亚胺制备的此类聚（氮丙啶）的脱磺酰化，以提供线性聚丙烯亚胺（L - PPI）作为L - PEI的替代品。研究了对甲苯磺酰化（Ts）和甲磺酰化（Ms）PPI的不同脱磺酰化策略。用双（2 - 甲氧基乙氧基）氢化铝钠对磺酰胺进行还原裂解，得到80%的脱保护胺基。当对甲苯磺酰化PPI在酸性条件下用对甲苯磺酸（pTsOH）在微波（MW）辐射下进行水解时，可实现向L - PPI的定量转化。相同的处理从甲磺酰化PPI类似物中去除了90%的甲磺酰基。与其他方法相比，微波辅助酸性水解是一种快速、廉价且简便的方法，其他方法的主要缺点是反应条件复杂和纯化繁琐，然而可能会发生一些断链现象。所得产物的高纯度，以及活性氮丙啶化学的多功能性，展示了我们策略的诸多优势，特别是对于未来的生物医学应用。
Linear polyethylenimine (L-PEI) has been the gold standard for gene delivery and is typically prepared by hydrolysis from poly(2-oxazoline)s. Recently, also the anionic polymerization of activated aziridines was reported as a potential pathway toward linear and well-defined polyamines. However, only sulfonamide-activated aziridines so far undergo the living anionic polymerization and their desulfonylation was only reported scarcely. This is mainly due to the relatively high stability of the sulfonamides and the drastic change in solubility during the desulfonylation. Herein, we investigated the desulfonylation of such poly(aziridine)s prepared from tosylated or mesylated propyleneimine to afford linear polypropylenimine (L-PPI) as an alternative to L-PEI. Different desulfonylation strategies for tosylated (Ts) and mesylated (Ms) PPI were studied. The reductive cleavage of the sulfonamide with sodium bis(2-methoxy ethoxy) aluminum hydride yielded 80% of deprotected amine groups. Quantitative conversion to L-PPI was obtained, when the tosylated PPI was hydrolyzed under acidic conditions with pTsOH under microwave (MW) irradiation. The same treatment removed 90% of the mesyl groups from the mesylated PPI analog. The MW-assisted acidic hydrolysis represents a fast, inexpensive and easy approach in comparison to other methods, where complex reaction conditions and tedious purifications are major drawbacks, however some chain scission may occur. The high purity of the obtained products, in combination with the versatility of the activated aziridine chemistry, demonstrate many advantages of our strategy, especially for future biomedical implementations.