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Updated: Oct 29, 2025

Split-and-pool Synthesis and Characterization of Peptide Tertiary Amide Library
Published on: June 20, 2014
Dipeptide Surrogates Containing Asparagine-Derived Tetrahydropyrimidinones: Structure and Amide Rotomer
Joseph P Konopelski1, Yunyang Wei1, Marilyn M Olmstead1
1Department of Chemistry and Biochemistry, University of California, Santa Cruz, California 95064, and Department of Chemistry, University of California, Davis, California 95616.
Abstract:
Novel dipeptide surrogates Fmoc-Xaa-(cyclo)Asn-OBu are prepared from asparagine, aromatic aldehydes, and Fmoc-protected amino acid chlorides. Previous studies have focused on basic approaches to key synthetic intermediates containing the (cyclo)Asn fragment for polypeptide preparation. The synthesis of these systems has now been extended to electron-rich aromatic aldehydes, exemplified by p-anisaldehyde. One-dimensional nuclear Overhauser effect experiments confirm the trans configuration around the central secondary amide bond and the boat conformation of the pyrimidinone ring. Variable-temperature NMR at 500 MHz was employed both to obtain thermodynamic data on the cis-trans amide bond interconversion barrier and to probe for the presence of hydrogen bonding. Single-crystal X-ray analysis of Ac-d-Ala-(cyclo)Asn-NHMe shows a high degree of structural similarity to a known proline-containing dipeptide.
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