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

The preparation of sequence-defined macromolecules using cyclic sulfamidates on solid-phase is outlined. The challenges surrounding an AB+CD approach are described with focus on understanding the formation of ring-opened side products when using amide coupling reagents. To avoid undesired side product formation, a strategy of iterative ring-openings of cyclic sulfamidates on solid-phase is explored. Ring-opening on primary and secondary amines is successfully reported, generating both linear and branched chain growth. However, attempts to selectively cleave N-sulfate bearing sp³ -hybridized groups cannot be demonstrated, limiting the overall building block scope for this methodology. Consequently, the active ring-opening of cyclic sulfamidates on amine-functionalized oligo(amidoamine) backbones is successfully applied to produce sequence-defined, N-sulfated macromolecules.