Combining Two Methods of Sequence Definition in a Convergent Approach: Scalable Synthesis of Highly Defined and Multifunctionalized Macromolecules

Graphical Abstract

Little by little: The first combination of efficient thiolactone chemistry and the Passerini three-component reaction (P-3CR) for the synthesis of sequence-defined macromolecules is reported. The thiolactone moiety was used as protecting group for the thiol, allowing the synthesis of a library of sequence-defined α,ω-functionalized building blocks. These building blocks were subsequently coupled to oligomers to give larger oligomers with molecular weights of up to 4629.73 g mol⁻¹ in gram quantities with up to 15 independently selectable side chains.

Abstract

The straightforward convergent synthesis of sequence-defined and multifunctionalized macromolecules is described herein. The first combination of two efficient approaches for the synthesis of sequence-defined macromolecules is reported: thiolactone chemistry and the Passerini three-component reaction (P-3CR). The thiolactone moiety was used as protecting group for the thiol, allowing the synthesis of a library of sequence-defined α,ω-functionalized building blocks. These building blocks were subsequently efficiently coupled to oligomers with carboxylic acid functionalities in a P-3CR. Thus, larger oligomers with molecular weights of up to 4629.73 g mol⁻¹ were obtained in gram quantities in a convergent approach along with the introduction of independently selectable side chains (up to 15), thus clearly demonstrating the high versatility and the efficiency of the reported approach.