Strategy for large-scale isolation of enantiomers in drug discovery.
A strategy for large-scale chiral resolution is illustrated by the isolation of pure enantiomer from a 5kg batch. Results from supercritical fluid chromatography will be presented and compared with normal phase liquid chromatography. Solubility of the compound in the supercritical mobile phase was shown to be the limiting factor. To circumvent this, extraction injection was used but shown not to be efficient for this compound. Finally, a method for chiral resolution by crystallization was developed and applied to give diastereomeric salt with an enantiomeric excess of 99% at a 91% yield. Direct access to a diverse separation tool box will be shown to be essential for solving separation problems in the most cost and time efficient way.
Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, Gothenburg 431 83, Sweden. Electronic address: hanna.leek@astrazeneca.com.
Hanna
H
Leek
Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, Gothenburg 431 83, Sweden.
Linda
L
Thunberg
Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, Gothenburg 431 83, Sweden.
Anna C
AC
Jonson
Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, Gothenburg 431 83, Sweden.
Kristina
K
Öhlén
Respiratory, Inflammation and Autoimmunity, Innovative Medicines, AstraZeneca R&D, Gothenburg 431 83, Sweden.
Magnus
M
Klarqvist
D025924:Chromatography, Supercritical Fluid / Q000379:methods*; D003460:Crystallization; D055808:Drug Discovery / Q000379:methods*; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry / Q000302:isolation & purification*; D012995:Solubility; D013237:Stereoisomerism
D004364:Pharmaceutical Preparations