Application of Assembly-line Synthesis to Conformationally Designed Cyclic and Acyclic Molecules

本项目描述了流水线合成在具有设计构象的环和非环分子中的应用，并详细研究了取代基对这些分子形状的影响。Aggarwal的流水线合成是一种独特的方法，它允许通过使用手性锂化氨基甲酸酯或酯作为构建块迭代同源化硼酸酯来生长碳链。该方法具有较高的保真度，不需要提纯中间体。尽管根据取代基的构型和位置控制长链烷基链的构象是一项具有挑战性的任务，但初步实验表明，可以实现对整体形状(如螺旋度)的控制。在这个项目中，将在更复杂的系统中探索作为主链距离的函数的构象控制的程度。此外，还将研究取代基对构象控制的限度。这将为不同大小的分子片段的精确相对定位提供机会。更好地理解构象控制将为具有前所未有的形状特异性的分子的合理设计铺平道路，例如，能够以高度选择性的方式结合到蛋白质表面。

This project describes the application of assembly-line synthesis to cyclic and acyclic molecules with designed conformation and the detailed investigation of the substituent effects on the shape of those molecules. Aggarwal's assembly-line synthesis is a unique method that allows to grow a carbon chain by iterative homologation of boronic esters using chiral lithiated carbamates or esters as building blocks. This method works with high fidelity and does not require purification of intermediates. Although conformational control of a long alkyl chain depending on the configuration and position of substituents represents a challenging task, initial experiments demonstrated that control of the overall shape (e.g. the degree of helicity) can be achieved. In this project, the extent of conformational control as a function of the distance from the main chain will be explored in more complex systems. Furthermore, limits of the conformational control by substituents will be studied. This will provide an opportunity for the precise relative positioning of molecular fragments of variable size. A better understanding of conformational control will pave the way to the rational design of molecules with unprecedented shape-specificity which could e.g. be capable of binding to protein surfaces in a highly selective manner.