High-performance liquid chromatographic separation and molecular modelling of diastereomeric isoindole derivatives of amino compounds

A high-performance liquid chromatography and molecular modelling study is presented for the diastereomeric adducts of a series of chiral thiol compounds and chiral amine compounds after reaction with o-phthalaldehyde (OPA). It is shown that the possibility of hydrogen bonds forming between the thiol and amino residues in the diastereomeric adducts is an important factor for obtaining good selectivity. The experimental elution orders were explained on the basis of the strength of the interaction between the polar groups of the thiol and amine constituents; it was found that the diastereomeric form having the largest distance between these groups always eluted first Moreover, within a series of OPA derivatives, the differences between the Boltzmann weighted averages of the distances between the polar groups of the two diastereomers show a good correlation with the experimental selectivities. (C) 1995 Wiley-Liss, Inc.