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Facile synthesis of mono-6-amino-6-deoxy-α-, β-, γ-cyclodextrin hydrochlorides for molecular recognition, chiral separation and drug delivery

Nature Protocols volume 3, pages 691–697 (2008)Cite this article

Abstract

We describe a protocol for the synthesis of mono-6-amino-6-deoxy-cyclodextrin hydrochloride (CD-NH3Cl), applicable to α-, β- and γ-cyclodextrin. These structurally simplest, highly water-soluble cationic cyclodextrins can be widely used in molecular recognition, chiral separation and drug delivery studies. Starting from commercially available chemicals, CD-NH3Cl is synthesized in four steps: (i) selective tosylation of cyclodextrin by the use of p-toluenesulfonyl chloride to afford mono-6-(p-toluenesulfonyl)-6-deoxy-cyclodextrin (Ts-CD); (ii) azide substitution of Ts-CD with sodium azide to afford mono-6-azido-6-deoxy-cyclodextrin (CD-N3); (iii) reduction of CD-N3 with triphenylphospine followed by hydrolysis to prepare mono-6-amino-6-deoxy-cyclodextrin (CD-NH2); and (iv) treatment of CD-NH2 with hydrochloric acid to afford the titled CD-NH3Cl with good yield. The overall protocol requires ∼2 weeks.

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Figure 8: Baseline separation of an eight-acid mixture using β-CD-NH3Cl with PDA detection at 254 nm.

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Acknowledgements

We are grateful to the National University of Singapore (NUS) and Institute of Chemical and Engineering Sciences, Singapore for financial support. W.T. expresses deepest gratitude to S.-C.N., Professor Chan Sze On, Hardy, Dr. Ong Teng Teng and Dr. I. Wayan Muderawan for their invaluable advice and great help in the completion of his research works on cationic cyclodextrins.

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  1. Department of Chemistry, National University of Singapore, Singapore, 117543, Singapore

    Weihua Tang

  2. Division of Chemical and Bimolecular Engineering, College of Engineering, Nanyang Technological University, Singapore, 627833, Singapore

    Siu-Choon Ng

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  1. Weihua Tang
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Correspondence to Weihua Tang or Siu-Choon Ng.

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Tang, W., Ng, SC. Facile synthesis of mono-6-amino-6-deoxy-α-, β-, γ-cyclodextrin hydrochlorides for molecular recognition, chiral separation and drug delivery. Nat Protoc 3, 691–697 (2008). https://doi.org/10.1038/nprot.2008.37

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