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.