Mass spectrometric studies shed light on unusual oxidative transformations of 1,2-dehydro-N-acetyldopa
Correspondence to: M. Sugumaran, Department of Biology, University of Massachusetts Boston, 100 Morrissey Blvd, Boston, MA 02125, USA.
Lamellarins are a group of over 70 plus bioactive marine natural compounds possessing a 6,7-dihydroxycoumarin moiety. Although they appear to derive from 3,4-dihydroxyphenylalanine (dopa), practically nothing is known about the metabolic fate of these compounds. Biochemical considerations indicate that they could arise from a N-acetyl-1,2-dehydrodopa precursor through oxidative cyclization reaction.
To assess the above hypothesis, we synthesized N-acetyl-1,2-dehydrodopa and conducted oxidation studies with commercially available mushroom tyrosinase and evaluated the course of the reaction with reversed-phase liquid chromatography/mass spectrometry (LC/MS).
Mushroom tyrosinase readily oxidized N-acetyl-1,2-dehydrodopa – not to the normally expected quinone – but to an unstable quinone methide isomer, which rapidly cyclized to produce the dihydroxycoumarin product, 3-aminoacetyl esculetin. Interestingly, 3-aminoacetyl esculetin was further oxidized to a second quinone methide derivative that exhibited an addition reaction with the parent dihydroxycoumarin generating dimeric and other oligomeric products in the reaction mixture.
LC/MS analysis of the N-acetyl-1,2-dehydrodopa oxidation reaction reveals not only a possible novel oxidative cyclization route for the biosynthesis of coumarin-type dehydrodopa compounds in marine organisms, but also unusual oxidative transformations of dehydro dopa derivatives. Copyright © 2013 John Wiley & Sons, Ltd.