ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

合成了两个N-取代的11-氮杂青蒿素系列化合物，并开发了一种新的10b-烷基脱氧青蒿素的合成方法。许多化合物在体外对恶性疟原虫耐药菌株的活性是先导化合物青蒿素的四到五倍。第一个系列包括碱催化的烯烃与各种电子撤回基团共轭的11-氮杂青蒿素的加成反应。第二个涉及二甲氨基吡啶催化的末端乙炔与11-氮杂青蒿素的加成反应。开发了由青蒿素合成10b-烷基脱氧青蒿素的新方法。合成过程包括用二异丁基铝氢化物还原青蒿素，然后进行乙酰化反应。后者与四氯化钛和一系列三甲基硅氧基烯醇醚反应，得到一系列10b-烷基脱氧青蒿素。测定了所有新化合物的抗疟活性。-疟疾、青蒿素、青蒿素衍生物的合成

Two series of N-substitutited 11-azaartemisinins were prepared and a new synthesis of 10b-alkyldeoxoartemisinis was developed. Many of the compounds were four or fives times more active in vitro against drug resistant strains of Plasmodium falciparum than the lead compound artemisinin. The first series involved a base catalyzed addition of olefins conjugated with a variety of electron withdrawing groups to 11- azaartemisinin. The second involved a dimethylaminopyridine catalyzed addition of terminal acetylenes conjugated to electron withdrawing groups to 11-azaartemisinin. The new synthesis of 10b- alkyldeoxoartemisinins from artemisinin was also developed. The synthesis involves redution of artemisinin by diisobutyl aluminum hydride followed by acetylation. The latter acetyl derivative was treated with titanium tetrachloride and a series of trimethylsiloxyl enol ethers to produce a series of 10b-alkyldeoxoartemisinins. The antimalarial activities of all new compounds were determined. - malaria, artemisinin, synthesis of artemisinin derivatives