6533b834fe1ef96bd129d667
RESEARCH PRODUCT
Analytical chemistry on many-center chiral compounds based on vibrational circular dichroism: Absolute configuration assignments and determination of contaminant levels
Susanne A. GooijerWybren Jan BumaWybren Jan BumaMark A. J. KoenisNadav U. JoostenEveline H. TiekinkValentin P. NicuLucas VisscherDavita M.e. Van Raamsdonksubject
Vibrational optical activity02 engineering and technologyCenter (group theory)01 natural sciencesBiochemistrySpectral lineAnalytical ChemistrySynthetic drugsSDG 3 - Good Health and Well-beingComputational chemistryStereochemistryEnvironmental ChemistryAbsolute configurationSpectroscopyFELIX Condensed Matter PhysicsChemistryDiastereomeric impurity levelsPharmaceutics010401 analytical chemistryAbsolute configurationDiastereomer021001 nanoscience & nanotechnology0104 chemical sciencesDensity functional calculationVibrational circular dichroism/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being0210 nano-technologyDensity functional calculationdescription
The absolute configuration of a chiral molecule is key to its biological activity. Being able to find out what this configuration is, is thus crucial for a wide range of applications. The difficulties associated with such a determination steeply rise as the number of chiral centers in a given compound becomes larger. Concurrently, it becomes increasingly more challenging to determine the levels and identity of potential stereochemical contaminants in a given sample with one and the same technique, leading in practice to extensive and laborious efforts employing multiple analytical techniques. Here, experimental and theoretical studies based on Vibrational Circular Dichroism (VCD) are presented for dydrogesterone, a synthetic drug employed in reproductive medicine that is a prototypical example of such a multi-center chiral compound. We show that our approach allows us to distinguish and assign its absolute configuration without prior knowledge to one of the 64 possible stereoisomers associated with the six chiral centers. Studies on mixtures of dydrogesterone and 6-dehydroprogesterone, one of the diastereomers of dydrogesterone and generally the dominant impurity of dehydrogesterone, show that we can identify the presence of both compounds from one single VCD spectrum. Moreover, we find that we can determine diastereomeric contamination levels as low as 5% from the experimental VCD spectra.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2019-12-20 |