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

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 NHSCN 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.

Stable hemiaminals from axially chiral pyridine compounds.

In this study, we have synthesized a series of 3-(pyridin-2-yl)-2-(pyridin-2-ylimino)thiazolidin-4-ol derivatives regioselectively from 2-iminothiazolidin-4-ones using LiAlH at room temperature. Due to the presence of the restricted rotation around the N3-C single bond, the formation of M/P isomers was observed. The OH group of the hemiaminal was found to orient itself on the same side with pyridyl nitrogen during this restricted rotation to form an intramolecular hydrogen bond, which was demonstrated by the computational DFT study.

Synthesis of thiazol-2-imines from the reduction of single enantiomer 2-imino-thiazolidin-4-ones followed by a spontaneous water elimination.

Chiral hemiaminals (5-8RR and 5-8SS) have been synthesized from the corresponding 2-iminothiazolidine-4-ones (1-4RR and 1-4SS) by LiAlH reductions stereoselectively and were then converted to single enantiomer thiazol-2-imines (9-12RR and 9-12SS) by a water elimination reaction. The kinetics of the dehydration reactions which occurred spontaneously both in the solid state and in the solution have been followed by time dependent H nuclear magnetic resonance spectroscopy. The corresponding first order rate constants and free energies of activation values for the conversions have been reported.

Asymmetric synthesis, molecular modeling and biological evaluation of 5-methyl-3-aryloxazolidine-2,4-dione enantiomers as monoamine oxidase (MAO) inhibitors.

Single enantiomers of the new 5-methyl-3-aryloxazolidine-2,4-diones have been obtained either by an asymmetric synthesis using the chiral pool strategy or by a semipreparative resolution of the racemic compound by HPLC on an optically active stationary phase. The single enantiomers were assayed for their in vitro monoamine oxidase (hMAO) inhibitory activity and selectivity. The most potent inhibitor among the studied compounds has been found as (5R)-3-phenyl-5-methyl-2,4-oxazolidinedione (compound 1-R) which appeared to be a good antidepressant drug candidate since it inhibited hMAO-A selectively, competitively and reversibly with K values in the micromolar range (0.