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

Abstract

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.

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References

  1. 1.

    Lutz JF, Lehn JM, Meijer EW, Matyjaszewski K. From precision polymers to complex materials and systems. Nat Rev Mater. 2016;1:16204.

    Article  Google Scholar 

  2. 2.

    Lutz JF, Ouchi M, Liu DR, Sawamoto M. Sequence-controlled polymers. Science. 2013;341:1238149.

    Article  Google Scholar 

  3. 3.

    Lutz JF. Defining the field of sequence-controlled polymers. Macromol Rapid Commun. 2017;38:12.

    Google Scholar 

  4. 4.

    Ouchi M, Sawamoto M. Sequence-controlled polymers via reversible-deactivation radical polymerization. Polym J. 2018;50:83–94.

    CAS  Article  Google Scholar 

  5. 5.

    Solleder SC, Schneider RV, Wetzel KS, Boukis AC, Meier MAR. Recent progress in the design of monodisperse, sequence-defined macromolecules. Macromol Rapid Commun. 2017;38:1600711.

    Article  Google Scholar 

  6. 6.

    Soejima T, Satoh K, Kamigaito M. J Main-chain and side-chain sequence-regulated vinyl copolymers by iterative atom transfer radical additions and 1:1 or 2:1 alternating radical copolymerization. Am Chem Soc. 2016;138:944–54.

    CAS  Article  Google Scholar 

  7. 7.

    Grate JW, Mo KF, Daily MD. Triazine-based sequence-defined polymers with side-chain diversity and backbone-backbone interaction motifs. Angew Chem Inter Ed. 2016;55:3925–30.

    CAS  Article  Google Scholar 

  8. 8.

    Hibi Y, Ouchi M, Sawamoto M. A strategy for sequence control in vinyl polymers via iterative controlled radical cyclization. Nat Commun. 2016;7:11064.

    Article  Google Scholar 

  9. 9.

    Wu YH, Zhang J, Du FS, Li ZC. Dual sequence control of uniform macromolecules through consecutive single addition by selective passerini reaction. ACS Macro Lett. 2017;6:1398–403.

    CAS  Article  Google Scholar 

  10. 10.

    Ji YX, Zhang LQ, Gu X, Zhang W, Zhou NC, Zhang ZB, et al. Sequence-controlled polymers with furan-protected maleimide as a latent monomer. Angew Chem Inter Ed. 2017;56:2328–33.

    CAS  Article  Google Scholar 

  11. 11.

    Kametani Y, Sawamoto M, Ouchi M. Control of the alternating sequence for N-Isopropylacrylamide (NIPAM) and methacrylic acid units in a copolymer by cyclopolymerization and transformation of the cyclopendant group. Angew Chem Inter Ed. 2018;57:10905–9.

    CAS  Article  Google Scholar 

  12. 12.

    Nowalk JA, Fang C, Short AL, Weiss RM, Swisher JH, Liu P, et al. Sequence-controlled polymers through entropy-driven ring-opening metathesis polymerization: theory, molecular weight control, and monomer design. J Am Chem Soc. 2019;141:5741–52.

    CAS  Article  Google Scholar 

  13. 13.

    Li J, Stayshich RM, Meyer TY. Exploiting sequence to control the hydrolysis behavior of biodegradable PLGA copolymers. J Am Chem Soc. 2011;133:6910–3.

    CAS  Article  Google Scholar 

  14. 14.

    Schmidt B, Fechler N, Falkenhagen J, Lutz JF. Controlled folding of synthetic polymer chains through the formation of positionable covalent bridges. Nat Chem. 2011;3:234–8.

    CAS  Article  Google Scholar 

  15. 15.

    Altintas O, Barner-Kowollik C. Single chain folding of synthetic polymers by covalent and non-covalent interactions: current status and future perspectives. Macromol Rapid Commun. 2012;33:958–71.

    CAS  Article  Google Scholar 

  16. 16.

    Rosales AM, Segalman RA, Zuckermann RN. Polypeptoids: a model system to study the effect of monomer sequence on polymer properties and self-assembly. Soft Matter. 2013;9:8400–14.

    CAS  Article  Google Scholar 

  17. 17.

    Nielsen PE. Peptide nucleic acid. a molecule with two identities. Acc Chem Res. 1999;32:624–30.

    CAS  Article  Google Scholar 

  18. 18.

    Horne WS, Gellman SH. Foldamers with heterogeneous backbones. Acc Chem Res. 2008;41:1399–408.

    CAS  Article  Google Scholar 

  19. 19.

    Fonseca AC, Gil MH, Simões PN. Biodegradable poly(ester amide)s - a remarkable opportunity for the biomedical area: review on the synthesis, characterization and applications. Prog Polym Sci. 2014;39:1291–311.

    CAS  Article  Google Scholar 

  20. 20.

    Basu A, Kunduru KR, Katzhendler J, Domb AJ. Poly(α-hydroxy acid)s and Poly(α-hydroxy acid-co-α-amino acid)s derived from amino acid. Adv Drug Deliv Rev. 2016;107:82–96.

    CAS  Article  Google Scholar 

  21. 21.

    Winnacker M, Rieger B. Poly(ester amide)s: recent insights into synthesis, stability and biomedical applications. Polym Chem. 2016;7:7039–46.

    CAS  Article  Google Scholar 

  22. 22.

    Shi CX, Guo YT, Wu YH, Li ZY, Wang YZ, Du FS, et al. Synthesis and controlled organobase-catalyzed ring-opening polymerization of morpholine-2,5-dione derivatives and monomer recovery by acid-catalyzed degradation of the polymers. Macromolecules. 2019;52:4260–9.

    CAS  Article  Google Scholar 

  23. 23.

    Llevot A, Boukis AC, Oelmann S, Wetzel K, Meier MAR. An update on isocyanide-based multicomponent reactions in polymer science. Top Curr Chem. 2017;375:66.

    Article  Google Scholar 

  24. 24.

    Koopmanschap G, Ruijter E, Orru RVA. Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics. Beilstein J Org Chem. 2014;10:544–98.

    Article  Google Scholar 

  25. 25.

    Bonne D, Dekhane M, Zhu JP. Mild oxidative one-carbon homologation of aldehyde to amide. J Am Chem Soc. 2005;127:6926–7.

    CAS  Article  Google Scholar 

  26. 26.

    Moore JS, Stupp SI. Room-temperature polyesterification. Macromolecules. 1990;23:65–70.

    CAS  Article  Google Scholar 

  27. 27.

    Pirrung MC, Das Sarma K. Aqueous medium effects on multi-component reactions. Tetrahedron. 2005;61:11456–72.

    CAS  Article  Google Scholar 

  28. 28.

    Sravan Kumar J, Jonnalagadda SC, Mereddy VR. An Efficient Boric acid-mediated preparation of α-hydroxyamides. Tetrahedron Lett. 2010;51:779–82.

    CAS  Article  Google Scholar 

  29. 29.

    Stayshich RM, Meyer TY. New insights into Poly(lactic-co-glycolic acid) microstructure: using repeating sequence copolymers to decipher complex NMR and thermal behavior. J Am Chem Soc. 2010;132:10920–34.

    CAS  Article  Google Scholar 

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Acknowledgements

This work was supported in part by the National Natural Science Foundation of China (Nos 21534001 and 21871014).

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Correspondence to Fu-Sheng Du or Zi-Chen Li.

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Wang, YZ., Wang, JC., Wu, YH. et al. Sequence-defined oligo/poly(ester-amide-ester)s via an orthogonal nucleophilic substitution reaction and a Passerini reaction. Polym J 52, 133–143 (2020). https://doi.org/10.1038/s41428-019-0272-6

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