10 The Absolute Configurations of the Metabolites of Acenaphthylene and Indene in Mammalian Systems
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When aromatic hydrocarbon is administered into a mammal, it is oxidized and excreted in urine partly as the optically active trans-dihydroxydihydro derivative. The knowledge of its absolute configuration is crucial for the study of chemical carcinogenesis as well as detoxication mechanism. We wish to report the absolute configurations of optically active trans-dihydroxydihydro metabolites of acenaphthylene and indene. (+)-trans-1, 2-Dihydroxyacenaphthene (I)a was obtained from the urine of rabbits, which had been injected subcutaneously with acenaphthylene. (+)-(I)a was acetylated with acetic anhydride and pyridine to give (-)-trans-1, 2-diacetoxyacenaphthene (I)b. Exhaustive ozonolysis of (-)-(I)b was carried out in acetic acid. The reaction product was treated with p-bromophenacyl bromide to afford (+)-di-O-acetyl di-p-bromophenacyl tartrate (V), which was found to be the derivative of (-)-tartaric acid. This fact indicates that (+)-(I)a has the 1R, 2R-configuration. (+)-trans-1, 2-Dihydroxyacenaphthene (I)a was converted to (-)-dibenzoate (I)c with benzoyl chloride and pyridine. Semiempirical calculation based on exciton theory was applied to the CD of (-)-(I)c, which confirmed the 1R, 2R-configuration of (+)-(I)a. The optical resolution of racemic trans-1, 2-dihydroxyindane (II)a via dimenthoxyacetate gave (-)-(II)a. Acetylation of (-)-(II)a with acetic anhydride and pyridine afforded (-)-trans-1, 2-diacetoxyindane (II)b. After exhaustive ozonolysis of (-)-(II)b in acetic acid, the reaction product was treated with diazomethane and column chromatography on silica gel afforded (+)-dimethyl threo-2, 3-diacetoxy-glutarate (VI), which was identified as the derivative of (-)-tartaric acid. This result means that (-)-(II)a has 1R, 2R-configuration, consequently its enantiomer (+)-(II)a, the metabolite of indene in rats, has 1S, 2S-configuration.
