Fine-Tuning Electroauxiliary-Mediated Peptide Modifications Using Second-Generation Electroactive Amino Acids

Arylthioether functional groups serve as effective electroauxiliariesfor tunable oxidations. Herein, we disclose the synthesis of second-generationglutamine building blocks bearing 2,4-dimethoxythiophenyl and 2,4-dichlorothiophenyl-derivedelectroauxiliaries. These building blocks improve SPPS efficiencyand enable fine-tuning of the electrochemical window for selectiveanodic oxidation reactions in comparison to first-generation 4-methoxythiophenyl-and 4-nitrothiophenyl-substituted variants. Installation onto a segmentof involucrin, a protein component of human skin, emphasizes the practicalapplication of the new building blocks for iterative functionalizations.

Automated summary

In this study, we report the synthesis of second-generation glutamine building blocks with electroauxiliaries derived from 2,4-dimethoxythiophenyl and 2,4-dichlorothiophenyl. These building blocks improve the efficiency of solid-phase peptide synthesis and allow for fine-tuning of the electrochemical window for selective anodic oxidation reactions. The practical application of these new building blocks for iterative functionalizations is demonstrated by their installation onto a segment of involucrin, a protein component of human skin.