Development of Fmoc-Protected Bis-Amino Acids toward Automated Synthesis of Highly Functionalized Spiroligomers

We report the fluorenylmethoxycarbonyl (Fmoc) protection of functionalized bis-amino acid building blocks using a temporary Cu2+ complexation strategy, together with an efficient multikilogram-scale synthesis of bis-amino acid precursors. This allows the synthesis of stereochemically and functionally diverse spiroligomers utilizing solid-phase Fmoc/tBu chemistry to facilitate the development of applications. Four tetramers were assembled on a semiautomated microwave peptide synthesizer. We determined their secondary structures with two-dimensional nuclear magnetic resonance spectroscopy.

Automated summary

This study reports the Fmoc protection of functionalized bis-amino acid building blocks using a temporary Cu2+ complexation strategy, along with an efficient multikilogram-scale synthesis of bis-amino acid precursors. Solid-phase Fmoc/tBu chemistry enables the synthesis of stereochemically and functionally diverse spiroligomers, promoting the development of applications. Four tetramers were assembled and their secondary structures were determined using two-dimensional nuclear magnetic resonance spectroscopy.