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Updated: Sep 23, 2025

Synthesis of Information-bearing Peptoids and their Sequence-directed Dynamic Covalent Self-assembly
Published on: February 6, 2020
Protecting-Group-Free Iterative Exponential Growth Method for Synthesizing Sequence-Defined Polymers
Zi Li1,2, Xiangzhu Ren1,2, Peng Sun1
1State Key Laboratory of Polymer Physics and Chemistry, Institute of Chemistry, The Chinese Academy of Sciences, Beijing 100190, People's Republic of China.
Abstract:
As a main synthetic strategy for monodisperse sequence-defined polymers, the known iterative exponential growth (IEG) methods were all developed on protecting-group chemistry, where the additional deprotection reactions increased their synthetic steps and decreased their atom economy. In this study, we developed a protecting-group-free IEG method for the formation of sequence-defined polymers by combining three orthogonal click reactions of copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC), sulfur-fluoride exchange reaction (SuFEx), and Ugi four-component reaction (Ugi-4CR). In this approach, oligomer synthesis began with three parallel CuAAC, SuFEx, and Ugi-4CR couplings among three monomers each with two orthogonal clickable end groups. By iteratively applying parallel CuAAC, SuFEx, and Ugi-4CR to couple three resultant oligomers, each having two orthogonal clickable terminals, this approach could exponentially grow three different sequence-defined polymers simultaneously with high efficiency, requiring no protecting-group chemistry. Additionally, each Ugi-4CR coupling reaction could introduce two external side groups to provide the molecular variation and side-chain functionalization for the resultant sequence-defined polymers.
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