Stationary Phases and Chromatographic Systems

Schulte, Michael; Jöhnck, Matthias; Skudas, Romas; Unger, Klaus K.; Hohenesche, Cédric du Fresne von; Wewers, Wolfgang; Dingenen, Jules; Kinkel, J.N.

doi:10.1002/9783527649280.ch3

Cited by 1 publication

(1 citation statement)

References 124 publications

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“…Other useful CSPs are the Pirkle-type Whelk-O1 phase [ 13 ] and the cinchona alkaloid–based weak anionic exchangers [ 14 ]. For the gram- to kilogram-scale amount of enantiomers required at the later stages of drug discovery and toxicological studies, chromatographic resolution via HPLC has been utilized for the past 25 years [ 15 , 16 , 17 ]. However, during the last decade the use of super critical fluid chromatography (SFC) has gained greater utility as a fast, cost-effective approach for the resolution of enantiomers [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Preparative Scale Resolution of Enantiomers Enables Accelerated Drug Discovery and Development

Leek

Andersson

2017

Molecules

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The provision of pure enantiomers is of increasing importance not only for the pharmaceutical industry but also for agro-chemistry and biotechnology. In drug discovery and development, the enantiomers of a chiral drug depict unique chemical and pharmacological behaviors in a chiral environment, such as the human body, in which the stereochemistry of the chiral drugs determines their pharmacokinetic, pharmacodynamic and toxicological properties. We present a number of challenging case studies of up-to-kilogram separations of racemic or enriched isomer mixtures using preparative liquid chromatography and super critical fluid chromatography to generate individual enantiomers that have enabled the development of new candidate drugs within AstraZeneca. The combination of chromatography and racemization as well as strategies on when to apply preparative chiral chromatography of enantiomers in a multi-step synthesis of a drug compound can further facilitate accelerated drug discovery and the early clinical evaluation of the drug candidates.

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