Synthesis of the chiral selector heptakis(6-O-methyl)-β-cyclodextrin by phase-transfer catalysis and hydrazine-mediated transfer-hydrogenation

Mihály Bálint, András Darcsi, Gábor Benkovics, Erzsébet Varga, Milo Malanga, S. Béni

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The exhaustive primary-side alkylation of cyclodextrins has never been achieved directly. The undesired and simultaneous derivatization of the secondary hydroxyl moieties generates intricate isomeric mixtures that are challenging to purify, analyse and characterize. The aim of this study was to develop a chromatography-free and up-scalable strategy towards the preparation of per-6-O-methylated cyclodextrin and to test the compound as potential chiral selector. The target molecule was prepared according to a five-step synthesis by using methyltriphenylphosphonium bromide as catalyst under heterogeneous conditions. The removal of benzyl moieties, used as temporary secondary-side protecting groups, was attained by applying hydrazine-carbonate in the presence of Pd/C. All the intermediates were obtained in high yields, thoroughly characterized and their purity was assessed by ad-hoc developed HPLC methods. The per-6-O-methylated β-cyclodextrin showed promising chiral recognition ability as background electrolyte additive in cyclodextrin-modified capillary electrophoresis using the recreational drug methylene-dioxypyrovalerone as model compound. Additionally, a model for the inclusion geometry between the single isomer host and the selected drug was developed based on the extensive 2D NMR analysis. The versatility of the proposed synthetic strategy opens the way to the industrial production of homogeneously primary-alkylated cyclodextrins and to their wide application in chiral separation of various drugs.

Original languageEnglish
JournalElectrophoresis
DOIs
Publication statusPublished - Jan 1 2019

Fingerprint

hydrazine
Hydrogenation
Cyclodextrins
Catalysis
Capillary electrophoresis
Carbonates
Alkylation
Capillary Electrophoresis
Street Drugs
Chromatography
Bromides
Isomers
Pharmaceutical Preparations
Hydroxyl Radical
Electrolytes
High Pressure Liquid Chromatography
Nuclear magnetic resonance
Catalysts
Molecules

Keywords

  • Enantioseparation
  • Methylated-cyclodextrin
  • NMR
  • Single isomer

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry

Cite this

Synthesis of the chiral selector heptakis(6-O-methyl)-β-cyclodextrin by phase-transfer catalysis and hydrazine-mediated transfer-hydrogenation. / Bálint, Mihály; Darcsi, András; Benkovics, Gábor; Varga, Erzsébet; Malanga, Milo; Béni, S.

In: Electrophoresis, 01.01.2019.

Research output: Contribution to journalArticle

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