ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

合成了一系列N-取代的11-氮杂青蒿素. 合成和几个成员被发现是四到五 在体外对耐药疟疾菌株的活性提高了一倍 先导化合物青蒿素，1.青蒿素的体内研究 2‘乙醛衍生物证实了体外实验结果。为了努力 进一步增加这一系列的活动一项特别工作组研究 承担了。为此，一条新的合成路线从 11-氮杂青蒿素被设计并用于制备 大约有十几种含有极性的化合物 3‘-碳上的基团。后一系列中最活跃的衍生品 体外活性也是1的4到5倍。 制备更活跃的衍生品的尝试正在进行中。 此外，一种使用N-取代11-氮杂青蒿素的程序 亲和层析柱的制备 已启动。该色谱柱将用于鉴定P. 与青蒿素衍生物结合或反应的恶性疟原虫。我们的 “青蒿素：一种内源性抗疟疾药物”综述 出现在《青蒿素化学进展》中 《有机天然产品》由施普林格-韦拉格出版社于1997年出版。

A series of N-substitutited 11-azaartemisinins were synthesized and several members were found to be four to fives times more active in vitro against drug resistant strains of malaria than the lead compound artemisinin, 1. An in vivo study of the 2'ethanal derivative confirmed the in vitro results. In an effort to increase further the activity of this series an SAR study was undertaken. For this purpose a new synthetic route from 11-azaartemisinin was devised and employed to prepare approximately a dozen additional compounds which contained polar groups on the 3'-carbon. The most active derivative in latter series was also four to five times more active in vitro than 1. Additional attempts to prepare more active derivatives are in progress.In addition, a program utilizing an N-substituted 11-azaartemisinin for the preparation of an affinity chromatographic column has been initiated. The column will be employed to identiy proteins from P. falciparum which bind or react with artemisinin derivatives. Our review on "Artemisinin: An Endoperoxidic Antimalarial from Artemisia annua L." appeared in "Progress in the Chemistry of Organic Natural Products" published by Springer-Verlag in 1997.