ASYMMETRIC SYNTHESIS--STRUCTURE, STEREOCHEMISTRY AND NMR

不对称合成——结构、立体化学和核磁共振

基本信息

批准号：
6289745
负责人：
Herman Ziffer
金额：
--
依托单位：
NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
依托单位国家：
美国
项目类别：
财政年份：
资助国家：
美国
起止时间：
至
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/6289745
关键词：
antimalarial agents autoradiography chemical structure function chemical substitution drug design /synthesis /production drug interactions molecular asymmetry nerve /myelin protein neurotoxicology nuclear magnetic resonance spectroscopy sesquiterpenes stereochemistry

项目摘要

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

制备了两个系列的N-取代的11-氮杂青蒿素，并开发了10b-烷基脱氧青蒿素的新合成方法。许多化合物在体外对抗恶性疟原虫耐药菌株的活性比先导化合物青蒿素高四到五倍。第一个系列涉及与各种吸电子基团共轭的烯烃与 11-氮杂青蒿素的碱催化加成。第二个涉及二甲氨基吡啶催化的与吸电子基团共轭的末端乙炔加成到 11-氮杂青蒿素上。还开发了以青蒿素为原料的10b-烷基脱氧青蒿素的新合成方法。合成过程包括用二异丁基氢化铝还原青蒿素，然后乙酰化。后者的乙酰基衍生物用四氯化钛和一系列三甲基硅氧基烯醇醚处理，产生一系列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