Enantiodifferentiation of Thiohydantoin Derivatives by NMR in the Presence of Chiral Solvating Agent: (1<i>R</i>,2<i>S</i>)-Ephedrine and Chiral Symmetrical and Unsymmetrical Thioureas

SARIGÜL ÖZBEK S., Tuncel S. T., Gunal S. E., Dogan I.

CHIRALITY, cilt.37, sa.2, 2025 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 37 Sayı: 2
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1002/chir.70013
  • Dergi Adı: CHIRALITY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Academic Search Premier, Applied Science & Technology Source, BIOSIS, Biotechnology Research Abstracts, Chemical Abstracts Core, Chimica, EMBASE, MEDLINE
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Evet

Özet

2-Thiohydantoin derivatives, including different substitutions at N-1 and C-5 (5-methyl-, 5-isopropyl-, 1-acetyl-5-methyl-, and 1-acetyl-5-isopropyl-) (1-4, respectively), were synthesized by the known literature methods. In these synthetic pathways, it was reported that enantiomerically pure 2-thiohydantions were obtained in the absence of any solvent via the reaction of L-amino acids with thiourea (1&2) and via the reaction of L-amino acids with NH4SCN and acetic anhydride (3&4). However, in this study, in contrary to the previous literature studies, racemic mixtures of 2-thiohydantoins were obtained although the same synthetic methods were used. The racemic nature of 2-thiohydantoin derivatives (1-4) was proved by using 1H NMR analysis in the presence of (1R,2S)-(-)-ephedrine as a chiral auxiliary. In addition, the enantiomers of 3&4 were also resolved on chiral stationary phases by HPLC analyses. Furthermore, newly synthesized unsymmetrical chiral thioureas (S-1&S-2) and previously synthesized symmetrical ones (SS-3&SS-4) were used as chiral solvating agent (CSA) for the enantiodiscrimination of the thiohydantoins (5&6), previously reported. Optimal CSA/substrate ratios were determined for the best enantiodiscrimination.