Herein, we
introduce the efficient synthesis of Q-proline (Q-Pro) based, metal-binding
macrocycles (QPM), which can display up to nine functional groups. Synthesis of
eight QPM was achieved through standard Fmoc-SPPS and peptoid chemistry. QPM are disordered in the absence of a
metal cation, as evidenced by NMR and a crystal structure of <b>QPM-3</b> obtained through racemic
crystallization. Addition of metal cations cause these macrocycles to adopt ordered,
uniform core structures regardless of the functional groups. Alkylation of QPM allows
for addition of reactive functional groups as the final step in a synthesis. Interestingly,
the addition of secondary functional groups to the hydantoin amide position (R<sub>2</sub>)
converts the proline ring from Cg-endo to Cg-exo, due to steric interactions.
Herein, we introduce the efficient synthesis of Q-proline (Q-Pro) based, metal-binding macrocycles (QPM), which can display up to nine functional groups. Synthesis of eight QPM was achieved through standard Fmoc-SPPS and peptoid chemistry. QPM are disordered in the absence of a metal cation, as evidenced by NMR and a crystal structure of QPM-3 obtained through racemic crystallization. Addition of metal cations cause these macrocycles to adopt ordered, uniform core structures regardless of the functional groups. Alkylation of QPM allows for addition of reactive functional groups as the final step in a synthesis. Interestingly, the addition of secondary functional groups to the hydantoin amide position (R2) converts the proline ring from C-endo to C-exo, due to steric interactions. 27 Pro 3-2 60 No >98 28 3-4 60 Yes 50 29 3-4 60* Yes >98 QP9 QP9 30 3-4 60* Yes >98 QP15
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.
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