NEW SYNTHESIS OF BIOCHEMICALS WITH HOMOGENEOUS CATALYSTS

我们研究的最终目标是设计和开发 合成邻苯二甲酸二异辛酯的多功能多催化剂体系 生物化学，使我们能够进行多步骤合成使用 以高度有序的方式将简单的原料放在一锅中。那些 复杂的催化剂系统最终可能会取代许多传统的 药物和其他生物合成方法 具有药用价值的活性化合物。 作为我们应对这一挑战的基本方法的延续 目标，我们将专注于开发新的和有效的方法 氮杂环的催化不对称合成，特别是 手性过渡金属催化剂促进的叠氮生物碱骨架 以及手性路易斯酸，在下一个供资期间(请求 四年)。拟议的研究包括以下四个项目： (1)氮杂环合成新方法的开发 通过络合控制的羰基化反应，我们将继续 我们成功地将络合控制的羰化反应应用于 多种吡咯里西酮、吲哚利嗪和喹诺利嗪的合成 基于新的环化反应的生物碱骨架 分子内烃化反应和非对映选择性 N-酰亚胺/N-酰亚胺离子与O-乙基半酰胺的反应 N-烯基酰胺分子内酰胺化反应易得 和烯胺类化合物；(2)新型不对称偶联反应的发展 手性促进N-酰亚胺和N-酰亚胺离子中间体的合成 刘易斯酸，在其中我们将探索那些非常有前途的小说 反应，为不对称碳-碳键的研究提供了有力的手段 (3)新型高效催化不对称化合物的开发 在这些过程中，我们将考察 不对称分子内手性铂和Rh催化剂 N-烯基酰胺和烯胺的酰胺化反应；(4)不对称 生物相关含氮杂环化合物的合成 手性均相催化剂，我们将在其中集成这三个 不对称合成多种叠氮类化合物的方法 项目1中选择的生物碱骨架以及藜芦碱，a 潜在的抗艾滋病和抗癌药物，也开发替代药物 不对称诱导的新方法。

The ultimate goal of our research is to design and develop multi-functional multi-catalyst systems for the synthesis of biochemicals, which enable us to carry out multi-step synthesis using simple starting materials in one-pot in a highly organized manner. Those sophisticated catalyst systems may eventually replace many conventional methods for the synthesis of pharmaceutical drugs and other biologically active compounds of medicinal interest. As the continuation of our fundamental approach to this challenging goal, we will focus on the development of new and efficient methods for the catalytic asymmetric synthesis of nitrogen heterocycles, especially izidine alkaloid skeletons, promoted by chiral transition metal catalysts as well as chiral Lewis acids, in the next funding period (requesting four years). The proposed research includes the following four projects: (1) Development of new methods for the synthesis of nitrogen heterocycles through chelation-controlled carbonylations, in which we will continue our successful applications of chelation-controlled carbonylations to the synthesis of various pyrrolizidine, indolizidine, and quinolizidine alkaloid skeletons through new annulation reactions based on intramolecular hydrocarbonylations as well as diastereoselective reactions of N-acylimine/N-acyliminium ion via O-ethyl hemiamidals readily obtained by intramolecular amidocarbonylation of N-alkenylamides and alkenamides; (2) Development of novel asymmetric coupling reactions of N-acylimine and Nacyliminium ion intermediates promoted by chiral Lewis acids, in which we will explore those highly promising novel reactions, providing powerful method for asymmetric carbon-carbon bond formation; (3) Development of new and efficient catalytic asymmetric hydrocarbonylation processes, in which we will examine the efficacy of chiral Pt and Rh catalysts in the asymmetric intramolecular amidocarbonylation of N-alkenylamides and alkenamides; (4) Asymmetric synthesis of nitrogenheterocycles of biological relevance by means of chiral homogeneous catalysts, in which we will integrate all three methodologies for the asymmetric synthesis of a variety of izidine alkaloid skeletons chosen in the project 1 as well as castanospermine, a potential anti-AIDS and anti-cancer drug, and also develop alternative new methods for asymmetric induction.