The effect of substituents on the chiral solvating properties of ( S)-1,6-dialkylpiperazine-2,5-diones

Abstract

The effect of substituents on the chiral solvating properties of 13 different ( S)-1,6-dialkylpiperazine-2,5-diones ( S)- 1a– m and five (3 S,6 S)-1,3,6-trialkyl analogues ( S, S)- 1n– r was studied by NMR in CDCl 3 with methyl ( RS)- N-benzoylleucinate ( RS)- 2a as the model analyte. Most diketopiperazines exhibited typical resolution, Δ Δ δ RS - 20 ∼0.1 ppm. Increased performance was observed with 6-CH 2R substituted compounds ( S)- 1h– j. The best resolution of the NH protons of ( R)- 2a and ( S)- 2a, Δ Δ δ RS - 20 = 0.227 ppm, was obtained with ( S)-1-isopropyl-6-(4-nitrobenzyl)piperazine-2,5-dione ( S)- 1j. An additional syn-oriented substituent at the C(3) position decreased the enantioselectivity. Association constants for the binding of ( S)- 1j to each enantiomer of ( RS)- 2a in CDCl 3 at −20 °C were determined by NMR titration.