Determining Stereoisomeric Excess and/or Concentration and/or Absolute Configuration of Chiral Compounds in a Sample

OVERVIEW

In the present invention, Georgetown University researchers have used highly modular, chirally flexible ligands known as “tropos ligands'' as circular dichroism probes for fast concentration/configuration analysis of chiral samples; in doing so, they avoid the time-consuming derivatization and purification steps required in conventional analysis. When a chiral analyte potentially contained in a sample comes into contact with the stereodynamic ligand, a stereodynamic complex is formed. The analyte coordinates with the metal center of the probe and initiates a chiral induction process that results in a spectroscopic signal change. The chiral information contained in the analyte stabilizes a distinct conformation or configuration of the stereodynamic metal complex, which can be correlated to the analyte’s stereoisomeric excess, and a change in the spectroscopic signal can be correlated to the analyte concentration.

BACKGROUND

Enantioselective synthesis and analysis are central to drug development and material science in addition to other burgeoning areas of research. The importance of chiral compounds in the pharmaceutical industry, particularly, has fueled the development of asymmetric catalysts and reaction strategies. Current optimization methods, however, do not efficiently probe the concentration and enantiomeric composition of chiral compound samples to maximize reaction potential.

Benefit

• Provides for fast concentration and stereoisomeric excess.
• High-throughput method accelerates the discovery process.
• Inexpensive way of sensing chirality in a large variety of chiral compounds.
• Minimizes waste production.

Market Application

• Evaluate high-throughput reactions whose desired product is chiral.
• Determine the stereoisomeric excess of the desired product, thus indicating the stereoselectivity of the reaction.
• Determine the concentration of the total product and/or the desired isomer, thus indicating the overall or individual yield of the reaction.
• High-throughput screening of chiral compounds to sense enantiomer presence, concentration, and configuration
• Optimization of reaction parameters, allowing the development, amplification, and modification of asymmetric catalysts, for instance.
• Enantiopurity assessment of compound samples.

Publications

• US patent No. 10,012,627
• “Chirality Sensing of Amines, Diamines, Amino Acids, Amino Alcohols, and α-Hydroxy Acids with a Single Probe” J. Am. Chem. Soc.
  2013, 135, 48, 18052–18055 https://doi.org/10.1021/ja410428b