Synthesis of Proline-Derived Helical Copolyacetylenes as Chiral Stationary Phases for HPLC Enantioseparation

Yue Li; Shu-Ming Kang; Ge Shi; Yi-Fu Chen; Bo-Wen Li; Jie Zhang; Xin-Hua Wan

doi:10.1007/s10118-024-3249-7

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Synthesis of Proline-Derived Helical Copolyacetylenes as Chiral Stationary Phases for HPLC Enantioseparation

RESEARCH ARTICLE | Updated：2024-12-31

- Synthesis of Proline-Derived Helical Copolyacetylenes as Chiral Stationary Phases for HPLC Enantioseparation
- Chinese Journal of Polymer Science Vol. 43, Issue 1, Pages: 61-69(2025)
- Affiliations：
  
  a.Beijing National Laboratory for Molecular Sciences, Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
  b.School of Materials Science and Engineering, Henan Joint International Research Laboratory of Living Polymerizations and Functional Nanomaterials, Henan Key Laboratory of Advanced Nylon Materials and Application, Zhengzhou University, Zhengzhou 450001, China
- Author bio：
  
  chenif@pku.edu.cn (Y.F.C.)
  xhwan@pku.edu.cn (X.H.W.)
- Funds：
- DOI：10.1007/s10118-024-3249-7
  CLC：
- Received：05 July 2024，
  
  Revised：2024-09-30，
  
  Accepted：11 October 2024，
  
  Online First：25 November 2024，
  
  Published：01 January 2025
- Accepted：
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Li, Y.; Kang, S. M.; Shi, G.; Chen, Y. F.; Li, B. W.; Zhang, J.; Wan, X. H. Synthesis of proline-derived helical copolyacetylenes as chiral stationary phases for HPLC enantioseparation. Chinese J. Polym. Sci. 2025, 43, 61–69

Yue Li, Shu-Ming Kang, Ge Shi, et al. Synthesis of Proline-Derived Helical Copolyacetylenes as Chiral Stationary Phases for HPLC Enantioseparation[J]. Chinese Journal of Polymer Science, 2025, 43(1): 61-69.
Li, Y.; Kang, S. M.; Shi, G.; Chen, Y. F.; Li, B. W.; Zhang, J.; Wan, X. H. Synthesis of proline-derived helical copolyacetylenes as chiral stationary phases for HPLC enantioseparation. Chinese J. Polym. Sci. 2025, 43, 61–69 DOI： 10.1007/s10118-024-3249-7.

Yue Li, Shu-Ming Kang, Ge Shi, et al. Synthesis of Proline-Derived Helical Copolyacetylenes as Chiral Stationary Phases for HPLC Enantioseparation[J]. Chinese Journal of Polymer Science, 2025, 43(1): 61-69. DOI： 10.1007/s10118-024-3249-7.

摘要

A series of optically active poly[(

)-2-ethynyl pyrrolidine)

]

derivatives with secondary amine groups were synthesized as chiral stationary phases. The secondary amine groups could form selective hydrogen bonds with racemates and increase the energy difference between the diastereomers formed by racemates and chiral stationary phases during HPLC enantioseparation.

Abstract

A series of optically active copolymers with various feed ratios have been synthesized through helix-sense-selective copolymerization catalyzed by [Rh(norbornadiene)Cl

]

-triethylamine. This process involves two proline-derived acetylene monomers

(

-(4-chlorophenyl)carbamoyl-2-ethynyl pyrrolidine (MCl) and (

tert

-butoxycarbonyl)-2-ethynyl pyrrolidine

followed by acidic deprotection and neutralization. These copolymers adopt helical conformations with a preferred handedness

as demonstrated by nuclear magnetic resonance spectroscopy and a series of spectroscopic analyses. The chiroptical activity intensity of copolymer has been found to increase with MCl content. Consequently

the enantioseparation capabilities of copolymers containing 95 mol%

90 mol%

and 85 mol% MCl units have been assessed as chiral stationary phases in high-performance liquid chromatography because of their good chiroptical activities. These chiral stationary phases effectively enantioseparate racemic alcohols

sulfoxides

amides

and metal complexes. Notably

the copolymer with 90 mol% MCl shows superior chiral recognition ability

especially for 1-(2

4-dichlorophenyl)-2-(1

-imidazol-1-yl)ethanol (

=1.19) and 4-methylbenzenesulfinamide (

=1.47). Insights from molecular dynamic simulation and autodock analysis indicate that hydrogen bonding and

acking interactions between the chiral stationary phases and enantiomers play a key role for successful chiral separation. Our contribution not only demonstrates the importance of hydrogen bonding donor and copolymer chiroptical activity of chiral stationary phases for chiral resolution

but will also provide valuable insights for the future development of novel stationary phases.

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references

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