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

Lebanon Valley College, Annville PA

Investigators

Abstract

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.