Preparation of cyclodextrin chiral stationary phases by organic soluble catalytic 'click' chemistry

Abstract

We describe an effective and simple protocol that uses click chemistry to attach native β-cyclodextrin (β-CD) to silica particles, resulting in a chiral stationary phase (CCNCSP) that can be used for the enantioseparation of chiral drugs by high-performance liquid chromatography (HPLC). Starting from β-CD, the CCNCSP is prepared in several steps: (i) reaction of β-CD with 1-(p-toluenesulfonyl)-imidazole to afford mono-6-toluenesulfonyl-β-CD; (ii) azidolysis of mono-6-toluenesulfonyl-β-CD in dimethylformamide to give mono-6-azido-β-CD (N3-CD); (iii) reaction of cuprous iodide with triphenylphosphine to form an organic soluble catalyst CuI(PPh3); (iv) preparation of alkynyl-modified silica particles; and (v) click chemistry immobilization of N3-CD onto alkynyl-modified silica to afford the desired chiral stationary phase. Synthesis of the stationary phase and column packing takes 1 week.

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Figure 5: HPLC enantioseparation of chiral drugs using 5- and 3-μm CCNCSP with diode array detector detection at 254 nm.

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Acknowledgements

Funding from the Singapore Ministry of Education Academic Research Fund Tier 2 (project number ARC 9/06) and an Agency for Science, Technology and Research SERC grant (grant no: 092 101 0056) in support of this project is gratefully acknowledged. Y.W. is grateful to Nanyang Technological University for the award of a Ph.D. scholarship.

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Y.W. designed the research; Y.W., H.C., Y.X., C.H.N. and T.S.O. carried out the synthesis experiments; Y.W. and H.C. performed the analytical experiments; Y.W., T.T.Y.T. and S.C.N. wrote the paper. All authors have discussed the results and approved the final manuscript.

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Correspondence to Timothy Thatt Yang Tan or Siu Choon Ng.

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The authors declare no competing financial interests.

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Wang, Y., Chen, H., Xiao, Y. et al. Preparation of cyclodextrin chiral stationary phases by organic soluble catalytic 'click' chemistry. Nat Protoc 6, 935–942 (2011). https://doi.org/10.1038/nprot.2011.340

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