RUI: Synthesis of Unnatural Amino Acids using Fmoc-protected N,O-Acetals

这个项目的目标是开发基于N，O-缩醛化学的合成策略，有效地导致Fmoc保护的非天然氨基酸。将探索基于三甲基硅基卤化物活化N，O-缩醛的无手性、Fmoc保护的α-、β-和伽马-氨基酸的合成方法，这一策略是对使用Lewis酸的传统方法的补充。还将研究使用硫脲类有机催化剂合成非天然α-和β-氨基酸的立体选择性策略。这些研究为本科生提供了在有机合成和不对称反应发展方面的广泛经验，并使学生接触到手性和生物有机化学问题。在化学合成计划的这一奖项的支持下，黎巴嫩山谷学院化学系的Timothy J.Peelen教授正在探索非天然氨基酸的合成。氨基酸是蛋白质和多肽的主要成分，在生物研究和潜在的治疗药物中是重要的分子。含有非天然侧链或替代骨架构型的氨基酸使化学家能够设计出具有天然低聚物所没有的性质的非天然的类蛋白质低聚物。该项目中的合成方法旨在以环境友好的方式更有效地制造非天然氨基酸构建块。该项目为本科生在化学研究方面提供了良好的培训。

This project targets the development of synthetic strategies, based upon the chemistry of N,O-acetals, that efficiently lead to Fmoc-protected unnatural amino acids. Synthetic methods that provide access to achiral, Fmoc-protected alpha-, beta-, and gamma-amino acids will be explored based upon activation of N,O-acetals using trimethylsilyl halides, a strategy that complements traditional approaches using Lewis acids. Stereoselective strategies for the synthesis of unnatural alpha- and beta-amino acids using thiourea-based organocatalysts will also be investigated. These studies provide undergraduate students with broad experience in organic synthesis and asymmetric reaction development and expose students to issues in chirality and bioorganic chemistry. With the support of this award from the Chemical Synthesis Program, Professor Timothy J. Peelen, of the Department of Chemistry at Lebanon Valley College, is exploring the synthesis of unnatural amino acids. Amino acids are the primary components of proteins and peptides, which are important molecules in biological research and potential therapeutic agents.Amino acids containing unnatural sidechains or alternative backbone configurations allow chemists to engineer unnatural, protein-like oligomers with properties not found in their natural counterparts. The synthetic approaches in this project target more efficient routes for making the unnatural amino acid building blocks in an environmentally friendly manner. This project provides excellent training for undergraduate students in chemical research.