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为了提高新霉胺对16S rRNA的亲和力,合成了Ⅱ环5位修饰的新霉胺类似物。以新霉素B为原料,经水解,保护,亲核取代,脱保护,叠氮还原多步反应得到氨基或氨基链修饰的新霉胺类似物。用表面等离子共振法测定了所合成的化合物与大肠杆菌(E.coli.)核糖体A位点rRNA(16S RNA)的相互作用。合成了6个Ⅱ环5-位修饰的新霉胺类似物,发现Ⅱ环5位氨基链修饰可以增强化合物对16S RNA的亲和力,其中一些化合物在10~(-3)M有体外细菌抑制活性。在新霉胺的Ⅱ环5位引入氨基或脂肪胺可以增加与16SRNA的亲和力。Ⅱ环5位上羟基的构型改变对于药物/16SRNA复合物稳定性的影响较低。
In order to improve the affinity of neamine for 16S rRNA, a neomycin analogue modified at position 5 of Ⅱ ring was synthesized. Using neomycin B as raw material, a new amidoamine analogue modified by amino group or amino chain was obtained by hydrolysis, protection, nucleophilic substitution, deprotection and azido reduction. The interaction between the synthesized compounds and ribosomal A site rRNA (16S RNA) of Escherichia coli was determined by surface plasmon resonance. Six novel neamine analogues modified at the 5-position of Ⅱ ring were synthesized and found that the modification of the amino group at the 5-position of Ⅱ ring enhanced the affinity of the compound to 16S RNA. Some of the compounds exhibited in vitro bacterial inhibitory activity at 10 -3 M . The introduction of amino or fatty amines at the 5 ’position of the neuraminidase can increase the affinity with 16SRNA. The structural change of the hydroxyl group at the 5-position of ring II has a relatively low effect on the stability of the drug / 16S RNA complex.