Epoc group: transformable protecting group with gold(iii)-catalyzed fluorene formation

Area of Science:

• Organic Chemistry
• Synthetic Chemistry
• Protecting Group Chemistry

Background:

• Protecting groups are crucial in multi-step organic synthesis.
• Orthogonality of protecting groups is essential for complex molecule construction, particularly in solid-phase peptide synthesis.
• Existing protecting groups often lack the desired stability and removal conditions for specific synthetic strategies.

Purpose of the Study:

• To introduce a novel concept of a transformable protecting group.
• To develop a new protecting group, the Epoc group, with unique transformation properties.
• To demonstrate the utility of the Epoc group in organic synthesis, specifically in solid-phase peptide synthesis.

Main Methods:

• Development of the 2-(2-ethynylphenyl)-2-(5-methylfuran-2-yl)-ethoxycarbonyl (Epoc) protecting group.
• Utilizing gold(iii)-catalyzed fluorene formation for structural transformation of the Epoc group.
• Investigating the stability and removal conditions of the transformed Epoc group under basic conditions.
• Assessing the orthogonality of the Epoc group in solid-phase peptide synthesis.

Main Results:

• The Epoc group was successfully synthesized and characterized.
• Gold(iii) catalysis transformed the Epoc group into an Fmoc-like structure.
• The transformed Epoc group exhibited mild basic removability, contrasting with its original stability under strong basic conditions.
• The Epoc group demonstrated novel orthogonality for gold(iii)-labile protecting groups in solid-phase peptide synthesis.
• High turnover numbers for fluorene formation in aqueous media were observed.

Conclusions:

• The Epoc group represents a novel class of transformable protecting groups.
• The Epoc group offers a new orthogonal protecting group strategy for solid-phase peptide synthesis.
• The demonstrated aqueous compatibility suggests potential applications in biological systems.