Preparation And Application Of Macrocyclic Antibiotics And Ligand Exchange Chiral Stationary Phases

Macrocyclic antibiotics-based chiral stationary phases have been attractingmore attention in recent years for it's broad application field, high loadability,robustness and stability. It has been a focus of research in chiral separation field todevelop novel synthesis methods and to research the enantiorecognition mechanismsof CSPs of this kind.An exclusive antibiotic of our country namely norvancomycin was used as anew chiral selector for the preparation of norvancomycin-bonded chiral stationaryphase (NVC-CSP). The possible mechanisms of chiral discrimination were alsodiscussed based on the enantioseparation of versatile structures of chiral compoundsunder different chromatographic modes. At the same time, phenyl carbamoylatednorvancomycin-bonded chiral stationary phase (PC-NVC-CSP) was also synthesizedusing phenyl isocyanate as derivative reagent, and a comparison for theenantioselectivity was made between NVC-CSP and PC-NVC-CSP.With the use of another macrocyclic antibiotic, teicoplanin, as chiral selector,two chiral stationary phases namely Tei-CSP I and Tei-CSP II were synthesizedadopting two different functionalized spacers. According to the enantioseparation ofamino acids, amino acids derivatives and chiral drugs, the possible chiral recognitionmechanisms were discussed. It was found experimentally that the enantioselectivity(α) for most chiral solutes on Tei-CSP II were less than that on Tei-CSP I, probablyfor the reason of interference from residual spacer.New ligand-exchange chiral stationary phases were synthesized utilizingL-hydroxyproline and L-isoleucine as chiral ligands via a simple preparation method.More than ten α-amino acids were tested on the newly synthesized CSPs in ligandexchange chromatography mode, and it was showed that part of them could bebaseline resolved under normal temperature because of higher ligand coverage of theCSPs. Five practical chromatographic methods were established for the chiralseparation of the enantiomers of three new chiral drugs, namely pantoprazole sodium,benproperine phosphate, zopiclone using the newly synthesized macrocyclicantibiotics-bonded CSPs and cyclodextrin-bonded CSP etc. In comparison with thosein published literatures, the new methods have the advantages of high columnefficiency, simplicity, and better repeatabilityetc.