The stepwise mammalian oxidation of the hydantoin 1-methylimidazolidine-2,4-dione into methylimidazolidinetrione via 5-hydroxy-1- methylimidazolidine-2,4-dione

Abstract

The metabolism of 1-methylhydantoin (2) is described. The major and general metabolic route in mammals, represented by formulae (2)→(7), includes two consecutive stepwise oxidations giving 5-hydroxy-1-methylhydantoin (3) and thence 1-methylparabanic acid (4). Since the first oxidation proved to be stereoselective, the step was thought to be enzymatic. Although enantiomeric products (3a) and (3b)(ca. 3 : 1) could not be separated directly, the mixture was converted into (S)- and (R)-5-(N-benzyloxycarbonyl-L-prolyloxy)-1-methylhydantoins (13a) and (13b) which proved separable and were identified by X-ray analysis of the (R)-diastereoisomer. The regioselective ring-fission of the second product (4) into the methyloxaluric acid (5) is discussed. Two minor oxidative routes from the substrate (2) into sarcosine (9) and parabanic acid (10) were also shown to exist.