Mass Spectrometry in Chiral Analysis and Synthesis

ABSTRACT

Mass spectrometry (MS) has a role to play in chiral chemistry, in part through methods based on microdroplets and non‐covalent molecular clusters. High‐throughput MS reaction screening and chiral anal0ysis use microdroplet sprays to perform accelerated nanoscale chemistry, including the synthesis of heterocyclics and other drug candidates using new high‐throughput automated instrumentation. The kinetic method of chiral analysis measures competitive dissociation reactions of molecular clusters (usually trinary coordination complexes) to determine enantiomeric excess (e.e.). A very different molecular cluster, the serine octamer, an active research topic for two decades, may hold implications in the search for the origins of homochirality. Lastly, the recently reported direct discrimination of enantiomers using an ion trap mass spectrometer (ITMS) is revisited. These four examples, combined with recent findings concerning chiral post‐translational modifications in cancer biology, represent exciting research developments that deploy the advantages of MS (throughput, molecular specificity, and sample size) to improve chiral synthesis and analysis.