Application of New Amination Reactions to Natural Product and Nonnatural Heterocy

该计划描述了一种化学合成路线，以生物活性的天然 产品.丝裂霉素C是一种临床上用于化疗的小分子， 作为DNA交联剂。没有其他已知的化疗重复 这种作用机制。一个简短的合成正在开发的基础上新的反应 在该计划的第一阶段：炔丙基亚胺的氮杂-Darfonyl反应 以非对映选择性地产生顺式氮丙啶。一种金属促进的胺-炔 然后，烯胺合成与醌配对以连接分子的两半。 合成的完成将通过本发明的几种中间体之一来完成。 方法提供。还完成了（+）-serratezomine A的全合成。 计划好了自由基介导的乙烯基胺化是其中的关键促成反应 合成. Serratezomine A是石松属生物碱的成员;许多成分 显示出乙酰胆碱酯酶抑制和抗癌活性。合成 路由允许通过 普通的骨骼结构 化学合成抗肿瘤和潜在的阿尔茨海默氏症治疗铅将 这些研究的结果。此外，具有更广泛影响的新合成方法 在药物合成中的应用。

This program describes a chemical synthesis route to biologically active natural products. Mitomycin C is a clinically-used small molecule for chemotherapy that functions as a DNA cross-linking agent. No other known chemotherapeutic duplicates this mechanism of action. A short synthesis is being developed based on new reactions devleoped during the program's first phase: the aza-Darzens reaction of propargyl imines to produce the cis-aziridine diastereoselectively. A metal promoted amine-alkyne enamine synthesis is then paired with a quinone to conjoin the molecule's two halves. Completion of the synthesis will be accomplished via one of several intermediates this approach provides. Completion of the total synthesis of (+)-serratezomine A is also planned. Free radical-mediated vinyl amination is a key enabling reaction in this synthesis. Serratezomine A is a member of the lycopodium alkaloids; many constituents have exhibited acetycholine esterase inhibition and anticancer activity. The synthesis route allows general access to these members and unnatural derivatives through a common skeletal construction. Chemical synthesis of antitumor and potential Alzheimer's therapeutic leads will result from these studies. Additionally, new synthetic methods with more general impact in pharmaceutical synthesis are expected to result.