自己会合により誘導される不斉識別法とその展開

抄録

In consideration of the flat-sheet structure known as a secondary structure of peptides and proteins, the self association of N-acyl α-amino acid derivatives may reasonably be expected to occur in non-aqueous media. To confirm the structure of dynamically formed molecular complexes, spectral studies of N-acetylvaline tert-butyl ester (1) in a carbon tetrachloride solution were carried out. A split of the amide NH resonance into two ¹H nmr signals for the D and L enantiomers, termed self-induced non-equivalence, was observed when the solute was enantiomerically enriched in the solution. A concentration study of ¹H and ¹³C-NMR showed the diastereomeric dimers, whose associative interactions are bidentate NH--O=C (ester) hydrogen bonds, to be in the enantiomeric solutions. Ir spectra confirmed the stability difference between the diastereomeric dimers by an external comparison of optically pure and racemic samples in the carbon tetrachloride solution.
The association stereoselectivity of solute 1 was applied to the design of chromatographic phase systems. When racemic solute 1 is injected into a non-chiral silica gel column using mobile phase solvent containing chiral solute 1 as an additive component, the racemate should interact with chiral solute 1 added to the mobile phase solvent, while passing through the column, to form transient diastereomeric dimers as observed in solution, and be separated. Self association-induced resolution was confirmed experimentally using radiolabelled solute 1 and the radioactivity detection.
Attempts were made to widen the scope of application involved in the hydrogen-bond association mode to chiral recognition through the development of other resolving agents. N-Acetylvaline tert-butylamide was found to separate the homologues of N-acyl α-amino acid esters. Tartaric esters and amides were found capable of separating a variety of enantiomeric compounds in non-aqueous media.