Chiral chromatography has a wide range of applications in the food, biochemical, and pharmaceutical industries.
Chiral chromatography has a wide range of applications in the food, biochemical, and pharmaceutical industries. For small molecule research it is extremely useful in the early development phases to isolate milligrams to low kilogram quantities of active isomers. Supercritical fluid chromatography (SFC) is frequently regarded as an more efficient separation technique for obtaining small amounts of pure enantiomers in this quantity range. It offers greater speed, reduced costs, and lower solvent consumption compared to liquid chromatography
An application for chiral chromatography in the preclinical phases of drug development is demonstrated in resolving a chiral pyrazole intermediate used in the synthesis of small molecule kinase inhibitor. In this application we present a example where a chiral method was developed for the separation of enantiomers of a substituted pyrrolo (2,3-J) pyrimidine intermediate formed in the synthesis of a novel kinase inhibitor.
The analytical screening was performed on a range of chiral columns to assess the separation of the racemic pyrrazole intermediate of interest. A published chiral method uses the normal phase HPLC conditions with a chiral stationary phase made of cellulose tris(3,5-dimethylphenyl carbamate) coated on silica gel. The analytical screening strategy confirmed the published method using RegisCell stationary phase. However, the selectivity for RegisCell was unsuccessful under SFC conditions. The (R,R)Whelk-O1 column performed well for the compound both in HPLC and SFC. This column typically shows complementary selectivity to polysaccharide type columns and it is useful for wide variety of racemates.
The new chiral SFC method for separation of intermediate enantiomer 1 and enantiomer 2 was ultimately developed using the (S,S)Whelk-O1 chiral column. The SFC screening may be complementary or reveal a better CSP for optimized method and productivity. In this application, (S,S)Whelk-O1 generated good resolution in HPLC and SFC, making this column an excellent choice for the analysis and potential scale up of this synthetic intermediate. The emergence of new technologies requires a reevaluation of current methods, so all available techniques and tools may be assessed well enough to choose the method that best suits the purpose of the project.
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Related Content:Application Notes: Chiral