De Franceschi Irene, Badi Nezha, Du Prez Filip E
Polymer Chemistry Research Group, Centre of Macromolecular Chemistry (CMaC), Department of Organic and Macromolecular Chemistry, Faculty of Sciences, Ghent University 9000 Ghent Belgium
Chem Sci. 2024 Jan 15;15(8):2805-2816. doi: 10.1039/d3sc04820a. eCollection 2024 Feb 22.
The application of sequence-defined macromolecules in material science remains largely unexplored due to their challenging, low yielding and time-consuming synthesis. This work first describes a step-economical method for synthesizing unnatural sequence-defined oligoamides through fluorenylmethyloxycarbonyl chemistry. The use of a monodisperse soluble support enables homogeneous reactions at elevated temperature (up to 65 °C), leading to rapid coupling times (<10 min) and improved synthesis protocols. Moreover, a one-pot procedure for the two involved iterative steps is demonstrated an intermediate quenching step, eliminating the need for in-between purification. The protocol is optimized using γ-aminobutyric acid (GABA) as initial amino acid, and the unique ability of the resulting oligomers to depolymerize, with the formation of cyclic γ-butyrolactame, is evidenced. Furthermore, in order to demonstrate the versatility of the present protocol, a library of 17 unnatural amino acid monomers is synthesized, starting from the readily available GABA-derivative 4-amino-2-hydroxybutanoic acid, and then used to create multifunctional tetramers. Notably, the obtained tetramers show higher thermal stability than a similar thiolactone-based sequence-defined macromolecule, which enables its exploration within a material context. To that end, a bidirectional growth approach is proposed as a greener alternative that reduces the number of synthetic steps to obtain telechelic sequence-defined oligoamides. The latter are finally used as macromers for the preparation of polymer networks. We expect this strategy to pave the way for the further exploration of sequence-defined macromolecules in material science.
由于其合成具有挑战性、产率低且耗时，序列定义的大分子在材料科学中的应用在很大程度上仍未得到探索。这项工作首次描述了一种通过芴甲氧羰基化学合成非天然序列定义的低聚酰胺的分步经济方法。使用单分散可溶性载体能够在高温（高达65°C）下进行均相反应，从而实现快速偶联时间（<10分钟）并改进合成方案。此外，展示了一种用于两个相关迭代步骤的一锅法，无需中间淬灭步骤，无需中间纯化。该方案以γ-氨基丁酸（GABA）作为起始氨基酸进行了优化，并证明了所得低聚物具有独特的解聚能力，形成环状γ-丁内酰胺。此外，为了证明本方案的通用性，从容易获得的GABA衍生物4-氨基-2-羟基丁酸开始合成了一个包含17种非天然氨基酸单体的文库，然后用于制备多功能四聚体。值得注意的是，所获得的四聚体显示出比类似的基于硫内酯的序列定义大分子更高的热稳定性，这使得能够在材料背景下对其进行探索。为此，提出了一种双向生长方法作为一种更环保的替代方法，可减少获得遥爪序列定义的低聚酰胺的合成步骤数量。后者最终用作制备聚合物网络的大分子单体。我们期望这种策略为在材料科学中进一步探索序列定义的大分子铺平道路。
