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消旋(±)-F18(10-chloromethyl-11-demethyl-12-oxo-calanolide A)是对天然产物(+)-calanolide A进行结构优化得到的四环香豆素类非核苷类逆转录酶抑制剂。本文建立了高效液相色谱法手性分离(±)-F18对映异构体的方法,并制备得到两个光学异构体(R)-F18和(S)-F18。应用电子圆二色谱技术和量化计算方法确定了二者光学异构体的绝对构型。抗HIV-1活性筛选表明,(S)-F18和(R)-F18对17个NNRTI耐药病毒株有相似的耐药谱,但二者的抗病毒活性有显著的区别。其中(R)-F18对野生型病毒株、K101E和P225H耐药株抗病毒活性较(S)-F18高近10倍。
10-Chloromethyl-11-demethyl-12-oxo-calanolide A is a tetracyclic coumarin non-nucleoside reverse transcriptase structurally optimized with the natural product (+) - calanolide A Inhibitors. In this paper, a method for the chiral separation of (±) -F18 enantiomers by high performance liquid chromatography was established and two optical isomers (R) -F18 and (S) -F18 were prepared. The absolute configuration of their optical isomers was determined by electronic circular dichroism and quantitative calculation. Screening of anti-HIV-1 activity showed that (S) -F18 and (R) -F18 had similar drug resistance spectrum to 17 NNRTI resistant strains, but there was a significant difference between their antiviral activities. Among them, the anti-virus activity of (R) -F18 against wild type and K101E and P225H resistant strains was nearly 10 times higher than that of (S) -F18.