The synthesis of sequence-defined, discrete starshaped macromolecules is a major challenge due to the lack of straightforward and versatile approaches. Here, a robust strategy is proposed that allows not only the preparation of sequence-defined mikto-arm star-shaped macromolecules but also the synthesis of a series of unprecedented discrete, multifunctional complex architectures with molar masses above 11 kDa. The iterative approach reported makes use of readily available building blocks and results in asymmetrically branched macromolecules with high purity and yields, which is showcased with monodisperse miktoarm three-, four-, and five-arm star-shaped structures that were all characterized via LC−MS, MALDI-ToF, and NMR. This effective strategy drastically improves upon synthetic abilities of polymer chemists by enabling simultaneously sequence definition, precision insertion of branching points, as well as the orthogonal endgroup functionalization of complex polymeric architectures. The presented approach, which can be translated to different platforms such as peptides and peptoids, is therefore particularly interesting in biomedical applications for which multiple different functional moieties on a single discrete macromolecule are needed.

Herein, a monodisperse soluble support is explored and used as an effective tool for the large-scale, liquid-phase synthesis of sequence-defined macromolecules. This support, based on a benzyl derivative with three...