NEW SYNTHESIS OF BIOCHEMICALS WITH HOMOGENEOUS CATALYSTS

使用均相催化剂合成生物化学品的新方法

• 批准号: 2179693
• 负责人: IWAO OJIMA
• 金额: $ 14.93万
• 依托单位: STATE UNIVERSITY NEW YORK STONY BROOK
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-09-01 至 1995-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2179693
• 关键词: alkaloids; aminoacid; antibiotics; carbonyl compound; castanospermine; catalyst; chemical bond; chemical reaction; chemical synthesis; metal complex; method development; nitrogenous heterocyclic compound; platinum; rhodium; stereochemistry

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.

我们研究的最终目标是设计和开发 多功能多催化剂体系， 生物化学品，这使我们能够进行多步合成， 简单的起始材料在一锅中以高度有组织的方式。 那些 复杂的催化剂系统最终可以取代许多传统的 用于合成药物和其它生物活性物质的方法 药用活性化合物。 作为我们应对这一挑战的基本方法的延续， 为了实现这一目标，我们将专注于开发新的有效方法， 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联苯双胍生物碱骨架 以及手性刘易斯酸，在下一个资助期（要求 四年）。 拟议的研究包括以下四个项目： (1)含氮杂环化合物合成新方法的研究进展 通过螯合控制的羰基化，我们将继续 我们成功地应用螯合控制羰基化反应， 各种吡咯里西啶、吲哚里西啶和喹里西啶合成 生物碱骨架通过新的成环反应， 分子内烃化以及非对映选择性 N-酰亚胺/N-酰亚胺离子通过O-乙基半酰胺醛的反应 通过N-烯基酰胺的分子内酰胺基羰基化容易地获得 （2）新型不对称偶联反应的发展 N-酰基亚胺和N-酰基亚胺离子中间体的手性促进 刘易斯酸，在其中我们将探索那些极具前景的新的 反应，为不对称碳-碳键提供了强有力的方法 （3）开发新型高效的催化不对称 加氢羰基化工艺，其中我们将检查的功效， 不对称分子内手性Pt和Rh催化剂 N-烯基酰胺和烯酰胺的酰胺基羰基化;（4）不对称 生物相关氮杂环化合物的合成 手性均相催化剂，其中我们将整合所有三个 各种对氮杂环丁烷的不对称合成方法 在项目1中选择的生物碱骨架以及栗精胺， 潜在的抗艾滋病和抗癌药物，并开发替代药物 不对称诱导的新方法