抗人免疫缺陷病毒(HIV)天然产物Calanolide A及其类似物的合成

SYNTHESIS AND ANTI-HIV ACTIVITY OF (±)-CALANOLIDE A AND ITS ANALOGUES

摘要: 目的：全合成抗爱滋病天然产物(±)-calanolide A。方法：以间苯三酚为原料，经4步化学反应按A-B-C-D环顺序合成。结果：全合成了(±)-calanolide A及未知化合物11-去甲基及6,6,11-去甲基calanolide A及B。结论：抗病毒筛选表明(±)-calanolide A能够明显抑制HIV-P_{24_{抗原在人PBMC细胞中的积聚，其IC₅₀为0.83 μm，治疗指数(TI,TC₅₀/IC₅₀)为34。}}

Abstract: AIM: To study the synthesis of (±)-calanolide A(5) and its analogues 11-demethyl and 6,6,11-demethyl calanolide A. METHODS AND RESULTS: (±)-Calanolide A(5) was synthesized by a four-step approach starting from phloroglucinol, via Pechmann reaction, Friedel-Crafts acylation, chromenylation and Luche reduction. (±)-Calanolide A analogues were also synthesized by the same methods. CONCLUSION: Anti-HIV test showed that the synthesized (±)-calanolide A markedly inhibited the accumulation of HIV-P₂₄ antigen in Human PBMC cell with an IC₅₀ of 0.83 μm and the therapeutic index (TI, TC₅₀/IC₅₀) was 34. The antiviral test of the analogues are in progress.