Synthesis of Tripeptide Derivatives with Three Stereogenic Centers and Chiral Recognition Probed by Tetraaza Macrocyclic Chiral Solvating Agents Derived from d‑Phenylalanine and (1<i>S</i>,2<i>S</i>)‑(+)-1,2-Diaminocyclohexane via ¹H NMR Spectroscopy

Enantiomers
of a series of tripeptide derivatives with three stereogenic
centers (±)-G1–G9 have been
prepared from d- and l-α-amino acids as guests
for chiral recognition by 1H NMR spectroscopy. In the meantime,
a family of tetraaza macrocyclic chiral solvating agents (TAMCSAs) 1a–1d has been synthesized from d-phenylalanine and (1S,2S)-(+)-1,2-diaminocyclohexane.
Discrimination of enantiomers of (±)-G1–G9 was carried out in the presence of TAMCSAs 1a–1d by 1H NMR spectroscopy. The results
indicate that enantiomers of (±)-G1–G9 can be effectively discriminated in the presence of TAMCSAs 1a–1d by 1H NMR signals of
multiple protons exhibiting nonequivalent chemical shifts (ΔΔδ)
up to 0.616 ppm. Furthermore, enantiomers of (±)-G1–G9 were easily assigned by comparing 1H NMR signals of the split corresponding protons with those attributed
to a single enantiomer. Different optical purities (ee up to 90%)
of G1 were clearly observed and calculated in the presence
of TAMCSAs 1a–1d, respectively. Intermolecular
hydrogen bonding interactions were demonstrated through theoretical
calculations of enantiomers of (±)-G1 with TAMCSA 1a by means of the hybrid functional theory with the standard
basis sets of 3-21G of the Gaussian 03 program.