Sequence-defined oligo/poly(ester-amide-ester)s via an orthogonal nucleophilic substitution reaction and a Passerini reaction

We report the facile synthesis of sequence-defined, uniform oligo(ester-amide-ester)s, and periodic poly(ester-amide-ester)s composed of ɑ-hydroxy acids and ɑ-amino acids. The synthetic strategy for preparing the oligomers involves two sequential steps with bromoacetic acid and potassium isocyanoacetate as the key building blocks. (1) The first step is a nucleophilic substitution reaction between a bromoacetic ester and potassium isocyanoacetate to generate a new isocyanoacetic ester, (2) and the second is a Passerini reaction of the formed isocyanoacetic ester with an aldehyde and bromoacetic acid to form a longer bromoacetic ester with an ester-amide linkage and a side-group originating from the aldehyde. Repeating this cycle affords sequence-defined uniform oligo(ester-amide-ester)s with different side groups. This strategy efficiently provides uniform, symmetrical oligo(ester-amide-ester)s via an iterative approach. Furthermore, two strategies were examined to obtain sequence-defined periodic poly(ester-amide-ester)s through the polycondensation of different oligomers. The polycondensation based on the nucleophilic substitution of α,ω-bromo carboxylic acids as the oligomer was less effective, while the DIC/DPTS-mediated polycondensation of α,ω-hydroxy carboxylic acids as the sequence-defined oligomer was efficient enough to afford high-molecular-weight periodic poly(ester-amide-ester)s. An efficient and straightforward strategy for the synthesis of uniform, sequence-defined oligo(ester-amide-ester)s via sequential nucleophilic substitution reactions and Passerini reaction was developed. The side groups could be easily regulated by the Passerini reaction of different aldehydes. The synthesis of uniform, symmetrical, long-chain oligomers was further demonstrated by an iterative approach. The DIC/DPTS-mediated polycondensation of the α,ω-hydroxy carboxylic acids as the sequence-defined oligomer afforded high-molecular-weight periodic poly(ester-amide-ester)s. The thermal properties of these oligo/poly(ester-amide-ester)s were also examined.