Synthesis of Nitrogen containing Building Blocks with Monothioester Malonates. An Efficient Method for alpha-, beta- and gamma-Amino Acid Derivatives

硫酯在自然界中的重要性是众所周知的，它们的化学效力被人体利用来创造生命的基本组成部分，如肽，脂肪酸和类固醇。该提议旨在在不对称有机催化中使用硫酯烯醇化物以实现高度对映体富集的、活化的α、β和γ氨基酸的合成。考虑到手性氨基酸衍生物不仅在蛋白质研究中很重要，而且也是许多药物和农用化学品的基础，这将是一项重大成就。该提案的每个阶段将开发不同链长和立体中心构型的方法，包括四元立体中心;然后展示其在合成已知生物活性底物中的应用，如抗生素，降胆固醇药物和抗糖尿病或帕金森病药物。同时开发的筛选方法将使快速合成和发现更有效的催化剂的开发方法。最终目标是创造一种通用工具，用于构建相邻立体中心的生物活性链，密切模仿天然对应物，如酶。

The importance of thioesters in nature is well established and their chemical potency is exploited by the human body to create the basic building blocks of life, such as peptides, fatty acids and steroids. This proposal aims to use thioester enolates in asymmetric organocatalysis to achieve the synthesis of highly enantioenriched, activated alpha, beta and gamma amino acids. This would be a significant achievement, considering that chiral amino acid derivatives are not only important in protein research, but also the basis of numerous pharmaceuticals and agrochemicals. Each phase of the proposal will develop methods for different chain lengths and configurations of stereocenters, including quaternary stereocenters; then demonstrate the application thereof in the synthesis of known biologically active substrates, such as antibiotics, cholesterol lowering drugs and drugs against diabetes or Parkinson disease. A simultaneously developed screening approach will enable the rapid synthesis and discovery of more efficient catalysts for the developed methodology. The ultimate goal is the creation of a universal tool for the construction of biologically active chains of adjacent stereocenters, closely mimicking natural counterparts, like enzymes.