Screening of a parallel combinatorial library for selectors for chiral chromatography

Area of Science:

• Analytical Chemistry
• Organic Chemistry
• Separation Science

Background:

• Developing efficient chiral selectors is crucial for enantioselective separations.
• Existing methods for screening chiral selectors can be time-consuming or require analyte immobilization.

Purpose of the Study:

• To describe a novel method for screening parallel combinatorial libraries of potential chiral selectors.
• To demonstrate the feasibility of this method using a model chiral high-performance liquid chromatography (HPLC) separation.

Main Methods:

• Efficient synthesis of potential chiral selectors directly on solid-phase synthesis resins.
• Rapid screening of resin-bound selectors using circular dichroism (CD) spectroscopy.
• Parallel library screening approach that avoids analyte immobilization.

Main Results:

• Successful demonstration of the parallel library screening method.
• Identification of effective chiral selectors from a small 16-member library.
• Achieved chiral HPLC resolution of (1-naphthyl)leucine ester using the screened selectors.

Conclusions:

• The described method provides an efficient and rapid approach for screening chiral selectors.
• This parallel screening technique complements existing mixture-based combinatorial library methods.
• The method offers a valuable tool for accelerating the discovery of novel chiral stationary phases for HPLC.