Exploring Cyclic Sulfamidate Building Blocks for the Synthesis of Sequence-Defined Macromolecules

Area of Science:

• Polymer Chemistry
• Organic Synthesis
• Macromolecular Science

Background:

• Solid-phase synthesis enables controlled macromolecular construction.
• Cyclic sulfamidates offer potential as building blocks for macromolecules.
• Amide coupling reagents can lead to undesired side products in macromolecular synthesis.

Purpose of the Study:

• To outline the preparation of sequence-defined macromolecules using cyclic sulfamidates on solid-phase.
• To investigate challenges in an AB+CD approach, focusing on side product formation with amide coupling reagents.
• To explore an iterative ring-opening strategy for cyclic sulfamidates to avoid side products and achieve controlled synthesis.

Main Methods:

• Utilizing cyclic sulfamidates on solid-phase for macromolecular assembly.
• Employing iterative ring-opening reactions with primary and secondary amines.
• Investigating the cleavage of N-sulfate bearing sp3-hybridized groups.

Main Results:

• Successful ring-opening of cyclic sulfamidates on primary and secondary amines, yielding linear and branched growth.
• Demonstrated limitations in selectively cleaving N-sulfate bearing sp3-hybridized groups.
• Achieved the production of sequence-defined, N-sulfated macromolecules via active ring-opening on amine-functionalized oligo(amidoamine) backbones.

Conclusions:

• Iterative ring-opening of cyclic sulfamidates on solid-phase is a viable strategy for synthesizing sequence-defined macromolecules.
• The methodology allows for controlled chain growth, producing both linear and branched structures.
• While effective for N-sulfated macromolecules, the scope is limited by challenges in cleaving certain N-sulfate bearing groups.