Beijing, March 23, 2018 – The requirement to produce chiral compounds as single enantiomers/diastereoisomers for pharmaceutical applications is well understood. The predominant method for generating chiral molecules, in the industry and at BioDuro, is via chiral resolution. On a small scale, resolving racemic compounds using chromatography either with chiral HPLC or SFC is fast and cost effective. However, as the scale increases to obtain multigram to kg of chiral material, SFC separation becomes prohibitively expensive and is no longer feasible.

Conversion of a racemate with a chiral resolving agent via chiral salt formation and subsequent separation of the mixture of diastereoisomers formed is known as the “classical method of resolution” that can be used whenever the target molecule contains a “salt handle”, i.e. either an amine or acid moiety. On scale in industry, two thirds of chiral resolution are being performed using classical salt formation with chiral resolving agents. The availability of screening methods to develop classical resolutions, the increased understanding of crystallizations and the ease of scale-up continue to make this the preferred methodology for many chiral molecules.

Recently, the scale up team at our Shanghai site undertook a systematic research on classical resolution and developed a robust resolution screening procedure for obtaining chiral compounds (see Figure 1). In particular, the method defined ways for rapidly screening for appropriate chiral agents and solvents suitable for a particular compound. Both of the two parameters are usually known as the hardest part for diastereoisomer salt formation and subsequent resolution. Utilization of this robust procedure was demonstrated by delivering several chiral amines successfully in hundreds of gram scale. We have built a collection of commercial chiral agents for resolving both racemic acids and amines and will continue to expand our ability to deliver even more robust chiral salt screening capability in the future.