Molecules by Assembly-Line Synthesis: Conformational Control and Biological Activity Study

流水线合成分子：构象控制和生物活性研究

• 批准号: 408172810
• 负责人: Dr. Lin Guo
• 金额: --
• 依托单位: School of Chemistry
• 依托单位国家: 德国
• 项目类别: Research Fellowships
• 财政年份: 2018
• 资助国家: 德国
• 起止时间: 2017-12-31 至 2019-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/408172810?language=en
• 关键词: Molecules; Assembly; Line; Synthesis; Conformational

Aggarwal's assembly-line synthesis represents a unique method that allows us to build a carbon chain by iterative homologation of boronic esters using chiral lithiated carbamates or esters as building blocks. The reaction shows high efficiency and complete stereocontrol in most cases, and its potential applicability has been further demonstrated with total syntheses of biologically active natural products. In this project, we propose to extend this methodology to the synthesis of conformationally designed molecules containing large substituents on side chains. We will investigate their three-dimensional structures by X-ray, advanced NMR and computational analysis, and determine the extent of conformational control remote from the main chain. This study will give us the knowledge of how to position molecular fragments with variable size in a precise position. In order to demonstrate the potential of this conformational control study, we will target helical structures with specific groups at specific places for optimum bonding to disrupt protein-protein interactions involved in cancer. We hope that the assembly-line synthesis along with conformational control study will enable us to rapidly build a series of biologically active compounds and facilitate new drug discovery.

Aggarwal 的流水线合成代表了一种独特的方法，使我们能够使用手性锂化氨基甲酸酯或酯作为结构单元，通过硼酸酯的迭代同系化来构建碳链。该反应在大多数情况下表现出高效率和完全的立体控制，其潜在的适用性在生物活性天然产物的全合成中得到了进一步证明。在这个项目中，我们建议将该方法扩展到侧链上含有大取代基的构象设计分子的合成。我们将通过 X 射线、先进的核磁共振和计算分析研究它们的三维结构，并确定远离主链的构象控制程度。这项研究将使我们了解如何将可变大小的分子片段定位在精确的位置。为了证明这项构象控制研究的潜力，我们将在特定位置针对具有特定基团的螺旋结构，以实现最佳结合，从而破坏与癌症有关的蛋白质-蛋白质相互作用。我们希望通过流水线合成和构象控制研究能够使我们能够快速构建一系列生物活性化合物并促进新药的发现。