Synthesis and Evaluation of Two Coumarin-Type Derivatization Reagents for Fluorescence Detection of Chiral Amines and Chiral Carboxylic Acids

The synthesis of two fluorescent coumarin-type chiral derivatization agents (4 and 11) is reported. A chiral side chain was introduced at position 7 of the coumarin via Mitsunobu reaction. The two coumarins bear in this side chain either a free amino group or a carboxyl group, making them useful for further transformations. Conjugates of chiral prototype drugs with 4 or 11 were prepared by amide coupling of the analyte's carboxyl group to the reagent's amine group, or vice versa. The separation of seven diastereomeric conjugates through achiral high-performance liquid chromatography (HPLC) on a common C18 column is demonstrated. Chirality 25:957-964, 2013. (c) 2013 Wiley Periodicals, Inc.