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

该项目旨在开发基于N， o -缩醛化学的合成策略，从而有效地产生受fmoc保护的非天然氨基酸。基于使用三甲基硅酰卤化物活化N， o -缩醛，这是一种补充使用刘易斯酸的传统方法的策略，将探索提供非手性，受fmoc保护的α， β和γ -氨基酸的合成方法。利用硫脲基有机催化剂合成非天然α -和β -氨基酸的立体选择性策略也将被研究。这些研究为本科生提供了有机合成和不对称反应发展的广泛经验，并使学生接触到手性和生物有机化学的问题。在化学合成项目的支持下，黎巴嫩谷学院化学系的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组成成分，是生物学研究中的重要分子，也是潜在的治疗药物。含有非天然侧链或替代主结构的氨基酸使化学家能够制造出非天然的、类似蛋白质的低聚物，这些低聚物具有天然氨基酸中所没有的特性。本项目中的合成方法旨在以更环保的方式更有效地制造非天然氨基酸构建块。本项目为本科学生的化学研究提供了良好的训练。

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.