Effects of a fluoro substituent on the fungal metabolism of 1-fluoronaphthalene.
The metabolism of 1-fluoronaphthalene by Cunninghamella elegans ATCC 36112 was studied. The metabolites were isolated by reverse-phase high-pressure liquid chromatography and characterized by the application of UV absorption, 1H nuclear magnetic resonance, and mass spectral techniques. C. elegans oxidized 1-fluoronaphthalene predominantly at the 3,4- and 5,6-positions to form trans-3,4-dihydroxy-3,4-dihydro-1-fluoronaphthalene and trans-5,6-dihydroxy-5,6-dihydro-1-fluoronaphthalene. In addition, 1-fluoro-8-hydroxy-5-tetralone, 5-hydroxy-1-fluoronaphthalene, and 4-hydroxy-1-fluoronaphthalene as well as glucoside, sulfate, and glucuronic acid conjugates of these phenols were formed. Circular dichroism spectra of the trans-3,4- and trans-5,6-dihydrodiols formed from 1-fluoronaphthalene indicated that the major enantiomers of the dihydrodiols have S,S absolute stereochemistries. In contrast, the trans-5,6-dihydrodiol formed from 1-fluoronaphthalene from 3-methylcholanthrene-treated rats had Cotton effects that are opposite in sign (R,R) to those formed by C. elegans. The results indicate that the fungal monooxygenase-epoxide hydrolase systems are highly stereoselective in the metabolism of 1-fluoronaphthalene and that a fluoro substituent blocks epoxidation at the fluoro-substituted double bond, decreases oxidation at the aromatic double bond that is peri to the fluoro substituent, and enhances metabolism at the 3,4- and 5,6-positions of 1-fluoronaphthalene.
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004851:Epoxide Hydrolases / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009090:Mucorales / Q000378:metabolism*; D009281:Naphthalenes / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet; D013329:Structure-Activity Relationship
D009281:Naphthalenes; C042963:1-fluoronaphthalene; D006899:Mixed Function Oxygenases; D004851:Epoxide Hydrolases