Regioselective protection of hydantoins – essential for hydantoin based anti-epileptic drugs

Abstract

The synthesis and NMR elucidation of six novel mono-and bis-Boc protected hydantoins are reported. The hydantoins 5-methylhydantoin, 5,5-dimethylhydantoin and a pentacycloundecane hydantoin exhibit an increase in substitution and steric hindrance at C-5. Kinetic and reagent controlled monoprotection of the smaller hydantoins achieve regioselective protection at N-1 while the bulky cage hydantoin is protected at N-3 . Hydantoin based anti-epileptic drugs such as 5,5-diphenylhydantoin require regioselective substitution at N-3 for enhanced pharmaceutical activity. The study enhances our understanding of the activity of the nitrogen atoms on hydantoin rings.

Interplay of thermochemistry and Structural Chemistry, the journal (volume 17, 2006) and the discipline

“…Kruger and Mdluli [71] in the next paper describe investigation of regioselective protection of hydantoins for the purpose of understanding the activity of the nitrogen atoms on hydantoin rings. Hydantoins can be applied as anti-epileptic drugs and 5,5-diphenylhydantoin is well known also for its anticonvulsant activity [72][73][74].…”

Crystal structure of 3-benzyl-5,5-dimethylimidazolidine-2,4-dione, C12H14N2O2

“…in dry N,N-dimethylformamide in the presence of potassium carbonate as ab ase [1,2]. The heterogeneous solution was heated at 85°Cfor six hours and concentrated in vacuo.…”

Synthesis and NMR elucidation of novel pentacyclo-undecane diamine ligands

“…However, the emergence of a range of standard 2D NMR techniques has helped a great deal in overcoming these problems. Our group has successfully used 2D NMR techniques to elucidate numerous PCU derivatives [12][13][14][15][16][17][18][19][20][21]. Odisitse et al [22] recently reported potent anti-inflammatory activity for the PCU diamine 9; this discovery led to the design and synthesis of compounds 3-8 which are currently being investigated as potential inflammatory agents while compounds 1 and 2 are precursors to 3 and 4. triethylamine was refluxed under nitrogen for 36 h to obtain the novel compounds 18 and 19.…”