Studies on the Synthesis of Novel Fluoroalkylated Compounds and Their Anti-HIV-1 Activity

以氟代烷酰基过氧化物为关键原料，通过碳-碳键的形成，将氟代烷基或氟代亚烷基引入到不同的底物中，合成了具有强选择性抗HIV-1活性的新型含氟化合物。利用氟代烷酰基过氧化物或高分子含氟有机过氧化物，合成了一系列含羧基、磺酸基和阳离子链段的氟烷基化或氟烯化低聚物，并研究了这些含氟低聚物的生物活性。这些化合物显示出具有有效的和选择性的抗HIV-1活性。有趣的是，这些氟化低聚物的抗HIV-1活性与它们的结构之间存在一些相关性，并且发现更亲油的低聚物，特别是含有硅链段的低聚物变得更有活性。此外，氟化磺酸低聚物 关于我们 在体外显示为HIV-1的有效和选择性抑制剂，并且对HIV-1的抑制比目前被认为是有效和选择性聚合物抑制剂的硫酸葡聚糖高约10倍。另一方面，不含阴离子而含阳离子链段的含氟低聚物对HIV-1复制无活性，但具有抗菌活性，不仅溶于水，而且溶于普通有机溶剂，能有效降低水的表面张力。此外，这些低聚物表现出类似于CMC的清晰的断裂点，这表明它们由于其独特的结构（氟烷基化封端结构）而在水溶液中形成分子内或分子间聚集体。因此，含氟低聚物分子内或分子间的聚集体可以部分地与病毒相互作用，从而对HIV-1的复制产生更强的抑制作用，有望作为具有抗HIV-1等生物活性的新型含氟功能材料应用于各个领域。少

Synthesis of novel fluorinated compounds possessing a potent and selecive anti-HIV-1 activity were studied by the introduction of fluoroalkyl or fluoroalkylene groups into various substrates with carbon-carbon bond formation by using fluoroalkanoyl peroxides as key materials. It was clarified that a series of fluoroalkylated or fluoroalkyleneated oligomers containing carboxyl, sulfo and cationic segments with carbon-carbon bond formation were prepared by using fluoroalkanoyl peroxides or polymeric fluorinated organic peroxides.The biological activities of these novel fluorinated oligomers thus obtained were studied. These compounds were shown to possess a potent and selective anti-HIV-1 activity. Interestingly, there was some correlation between the anti-HIV-1 activity of these fluorinated oligomers and their structures, and the more oleophilic oligomers, especially oligomers containing silicon segments were found to become more active. Furthermore, fluorinated sulfonic acid oligomers … More were shown to be potent and selective inhibitors of HIV-1 in vitro, and about 10-times more inhibitory to HIV-1 than dextran sulfate which is considered at present to be a potent and selective polymeric inhibitor. On the other hand, fluorinated oligomers containing not anionic but cationic segments were inactive against HIV-1 replication ; however, they possessed antibacterial activity.These novel fluorinated oligomers were soluble in not only water but also in common organic solvents, and were able to reduce the surface tension of water effectively. In addition, these oligomers exhibited a clear break point resembling a CMC,which suggest that they form intra-or inter-molecular aggregations in aqueous solutions owing to their unique stucture (fluoroalkylated end-capped structure). Hence, it was suggested that intra-or inter-molecular aggregation of fluorinated oligomers would interact in part with virus leading to more potent inhibitory effects against HIV-1 replication.In this way, our present fluorinated oligomers are much expected to be applicable in various fields as new fluorinated functional materials possessing biological activities such as anti-HIV-1 activity. Less