Homo- and hetero-difunctionalized β-cyclodextrins: Short direct synthesis in gram scale and analysis of regiochemistry

Gábor Benkovics, Mihály Bálint, Éva Fenyvesi, Erzsébet Varga, S. Béni, Konstantina Yannakopoulou, Milo Malanga

Research output: Contribution to journalArticle

Abstract

The regioselective difunctionalization of cyclodextrins (CDs) leading to derivatives amenable to further transformations is a daunting task due to challenging purification and unambiguous characterization of the obtained regioisomers with similar physico-chemical properties. The primary-side homo-difunctionalization of β-CD can lead to three regioisomers, while the hetero-difunctionalization can generate three pairs of pseudoenantiomers. Previously, approaches with several synthetic steps, expensive reagents, high purification demands and low yields of the products have been employed. Herein we present direct, short and efficient primary-side difunctionalization strategies featuring reproducibility, ease of product purification, scalability of the reactions and versatility of the substituents introduced. Specifically, the prepared ditosylated β-CDs were separated using preparative reversed-phase column chromatography and their structures were elucidated by NMR experiments. Azidation led to the corresponding pure diazido regioisomers. Direct monotosylation of 6-monoazido-β-CD or monoazidation of the single regioisomers 6 A ,6 X -ditosyl-β-CDs afforded hetero-difunctionalized 6 A -monoazido-6 X -tosyl-β-CDs in significant yields. Overall, the single regioisomers, 6 A ,6 X -ditosyl-, 6 A ,6 X- diazido- and 6 A -monoazido-6 X -monotosyl-β-CD were prepared in one or two steps and purified in multigram scale thus opening the way towards further selective and orthogonal functionalizations of β-CD hosts.

Original languageEnglish
Pages (from-to)710-720
Number of pages11
JournalBeilstein Journal of Organic Chemistry
Volume15
DOIs
Publication statusPublished - Mar 18 2019

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Keywords

  • Azido-tosyl-cyclodextrin
  • Diazido-cyclodextrin
  • Hetero-difunctionalization
  • Homo-difunctionalization
  • Regioselectivity

ASJC Scopus subject areas

  • Organic Chemistry

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