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

作　　者：周春梅[1] 王琳[1] 张铭龙 赵知中[1] 张兴权[2] 陈湘红[2] 陈鸿珊[2] 

机构地区：[1]中国医学科学院,中国协和医科大学药物研究所,北京100050 [2]中国医学科学院,中国协和医科大学医药生物技术研究所,北京100050

出　　处：《药学学报》1999年第9期673-678,共6页Acta Pharmaceutica Sinica

基　　金：国家自然科学基金

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 Ｈ Ｉ Ｖ Ｐ２ ４ 抗原在人 Ｐ Ｂ Ｍ Ｃ 细胞中的积聚，其 Ｉ Ｃ５ ０ 为０８３ μｍ ，治疗指数（ Ｔ Ｉ， Ｔ Ｃ５ ０ ／ Ｉ Ｃ５ ０ ） 为３４ 。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 P 24 antigen in Human PBMC cell with an IC 50 of 0 83 μm and the therapeutic index (TI, TC 50 /IC 50 ) was 34 The antiviral test of the analogues are in progress.

关 键 词：天然产物 CalanolideA 合成 抗HIV病毒活性 

分 类 号：R978.7[医药卫生—药品]