ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

合成了两个系列的N-取代11-氮杂青蒿素，并开发了10 b-烷基脱氧青蒿素的新合成方法。许多化合物在体外对恶性疟原虫耐药株的活性是主要化合物青蒿素的四倍或七倍。第一个系列涉及碱催化加成烯烃共轭与各种吸电子基团的11-氮杂青蒿素。 第二个涉及二甲基氨基吡啶催化加成末端乙炔共轭吸电子基团11-azaartemisinin。 还开发了以青蒿素为原料合成10 b-烷基脱氧青蒿素的新方法。青蒿素的合成包括氢化二异丁基铝还原，然后乙酰化。 后者的乙酰基衍生物与四氯化钛和一系列的三甲基异丙基烯醇醚处理，产生一系列的10 b-烷基脱氧青蒿素。 测定了所有新化合物的抗疟活性。第三系列的化合物是通过酸催化的迈克尔加成到青蒿素中来制备的。 这些化合物的活性是青蒿素的四到七倍。

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 seven 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. A third series of compounds were prepared by acid catlyzed Michael additions to artemisitene. The compounds were four to seven times more active than artemisinin.