Metabolism of nafronyl in man

The metabolism of nafronyl (I) has been studied in man. In addition to small amounts of the parent compound, three acidic metabolites were extracted from urine. The chemical structures of all metabolites were determined by using mass spectrometry and [1H]-NMR spectroscopy as tetrahydro-beta-(1-nephthalenylmethyl)-2-furanpropionic acid (II) and two stereoisomers of 3-(1-naphthalenylmethyl)-tetrahydrofuran-2-one-5-propionic acid (III, IV). The biodegradation products III and IV are formed after oxidation of the tetrahydrofuran system in II, hydrolytic ring opening of the gamma-butyrolacton and a subsequent formation of a gamma-butyrolacton ring with the second carboxyl group. The three metabolites represent the major fraction of unconjugated products in the urine of man after administration of nafronyl.