4-Oxoimidazolidine derivatives

Syntheses of hydantoin compounds from 1,3,5-triaza-7,7,9,9-tetramethylspiro[4.5]decane-2,4-dione (61) were also planned, since derivatives of this type showed high activity compared to oxazoli-dones and 4-oxoimidazolidines. Further, three different types of... 

As an example, ferf-butyl (45)-l-methyl-2-oxoimidazolidine-4-carboxylate was used by Nunami and colleagues as a chiral auxiliary for DKR of a-bromo-carboxylic acids. In this case, the nucleophile was a malonic ester enolate and the role of the polarity of the solvent (hexamethylphosphoramide, HMPA) was demonstrated (Scheme 1.2). The alkylated products were further easily converted to chiral a-alkylsuccinic acid derivatives and chiral jS-amino acid derivatives. Moreover, these authors showed that this methodology could be extended to other nucleophiles such as amines." Therefore, the reaction of a diastereomeric mixture of tert-bvAy (45)-l-methyl-2-oxoimidazolidine-4-carb-oxylate with potassium phthalimide predominantly afforded fcrf-butyl (45)-1-methyl-3-((25)-2-(phthaloylamino)propionyl)-2-oxoimidazolidine-4-carboxylate in 90% yield and 94% diastereomeric excess (de). The successive removal of the chiral auxiliary afforded A-phthaloyl-L-alanine. 

In order to determine the taste modulating activity of the identified compounds, triangle tests were performed with the purified compounds dissolved in water (for intrinsic taste) as well as in a model broth solution (for taste modulatory activity), respectively. None of the compounds 1-5 showed any intrinsic taste up to a maximum concentration of 1000 pmol/kg, but all these creatinine derivatives imparted taste modulating activity in model broth by enhancing its thick-sour, brothy taste. The lowest threshold concentration of 76 pmol/kg was found for 4-hydroxy-2-A-(l-methyl-4-oxoimidazolidin-2-ylideneamino) butanoic acid (3), whereas the highest threshold level of 489 pmol/kg was determined for 4-hydroxy-2-77-(l -methyl-4-oxoimidazolidin-2-ylideneamino)pentanoic lactone (4) (Table 1). 

It should be noted that self-condensation of aminonitriles to 4-oxo-imidazolidines is accompanied by the formation of sterically hindered piperazine derivatives, the starting compounds for nitroxides of the piperazine series (Yoshioka et al, l972b). Stable 4-oxoimidazolidine nitroxides, as well as piperidine derivatives, have been patented as heat and light stabilizers, inhibitors, etc. (see Murayama et al, 1976). 

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