Chiral Stationary Phases Derived from Cinchona Alkaloids

Lämmerhofer, Michael; Lindner, Wolfgang

doi:10.1002/9781119802280.ch11

Cited by 6 publications

(1 citation statement)

References 116 publications

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“…The most popular chiral columns are based on cellulose and amylose derivatives [6,7], macrocyclic glycopeptide antibiotics (vancomycin, teicoplanin, and its aglycon) [8], cyclodextrins [8], cyclofructans [9], chiral crown ethers [10], synthetic donor-acceptor (Pirkle) type CSPs (e.g., Whelk O1) [11], and quinine (QN)/quinidine (QD) carbamate type chiral ion-exchangers [12][13][14]. In recent years, also UHPLC versions based on sub-2 µm fully porous particles or sub-3 µm superficially porous particles of many of above-mentioned CSPs have been introduced into the market [15,16].…”

Section: Introductionmentioning

confidence: 99%

Cross‐linked polysiloxane‐coated stable bond O‐9‐(2,6‐diisopropylphenylcarbamoyl)quinine and quinidine chiral stationary phases as well as application in enantioselective cryo‐HPLC

Woiwode,

Sievers‐Engler,

Lämmerhofer

2023

Electrophoresis

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In this work, brush‐type chiral stationary phases (CSPs) with O‐9‐(2,6‐diisopropylphenylcarbamoyl)‐modified quinidine (DIPPCQD‐brush/‐SH) and O‐9‐(2,6‐diisopropylphenylcarbamoyl)‐modified quinine (DIPPCQN‐brush/‐SH) were prepared as benchmarks for comparison with new corresponding polymeric CSPs with more stable bonding chemistry. These polymeric CSPs were prepared by coating a thin poly(3‐mercaptopropyl)‐methylsiloxane film together with the chiral selector onto vinyl‐modified silica. In a second step, immobilization of the quinine/quinidine derivatives as well as cross‐linking of the polysiloxane film to the vinyl‐silica is achieved by a double thiol‐ene click reaction. The polymeric CSPs exhibited similar enantioselectivity as the corresponding brush phases, but showed lower chromatographic efficiencies. Chiral acidic substances were separated into enantiomers (e.g., N‐protected amino acids, herbicides like dichlorprop) in accordance with an enantioselective anion‐exchange process. Oxidation of residual thiol groups of the polymer DIPPCQN‐CSP introduced sulfonic acid co‐ligands on the silica surface, which resulted in greatly reduced retention times. Acting as immobilized counterions, they allowed to reduce the concentration of counterions in the mobile phase, which is favorable for liquid chromatography (LC)–electrospray ionization–mass spectrometry application. Ibuprofen showed a single peak under ambient column temperature. However, application of cryogenic cooling of the column enabled to achieve baseline separation at –20°C column temperature. It can be explained by an enthalpically dominated separation, which leads to an increase in separation factors when the temperature is reduced. While it is quite uncommon to work at subzero degree column temperature, this work illustrates the potential to exploit such temperature regime for optimization of LC enantiomer separations.

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Section: Introductionmentioning

confidence: 99%

Cross‐linked polysiloxane‐coated stable bond O‐9‐(2,6‐diisopropylphenylcarbamoyl)quinine and quinidine chiral stationary phases as well as application in enantioselective cryo‐HPLC

Woiwode,

Sievers‐Engler,

Lämmerhofer

2023

Electrophoresis

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Biosynthetic Origin of the Methoxy Group in Quinine and Related Alkaloids

Lombe,

Zhou,

Caputi

et al. 2024

Angewandte Chemie

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a methoxy group that has been assumed to be incorporated at a late pathway stage. Here we show that the methoxy group in quinine and related alkaloids is introduced onto the starting substrate tryptamine. Feeding studies definitively show that 5‐methoxytryptamine is utilized as a quinine biosynthetic intermediate in planta. We discover the biosynthetic genes that encode the responsible oxidase and methyltransferase, and we use these genes to reconstitute the early steps of the alkaloid biosynthetic pathway in Nicotiana benthamiana to produce a mixture of methoxylated and non‐methoxylated alkaloid intermediates. Importantly, we show that the co‐occurrence of both tryptamine and 5‐methoxytryptamine substrates, along with the substrate promiscuity of downstream pathway enzymes, enable parallel formation of both methoxylated and non‐methoxylated alkaloids.

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