Labeling Pattern of Okadaic Acid from 18O2 and [18O2]Acetate Elucidated by Collision-Induced Dissociation Tandem Mass Spectrometry

Okadaic acid ( 1 ) is a polyether compound produced by the marine dinoflagellate Prorocentrum lima . Its biosynthesis attracts considerable attention since the carbon skeleton has been shown to be synthesized via an unusual route. However, a very limited amount of information is available for the formation of its ether rings. We applied collision-induced dissociation tandem mass spectrometry (CID MS/MS) to the elucidation of the 18 O-incorporation pattern of okadaic acid. The extensive determination of 18 O/ 16 O ratios for each product ion bearing differing numbers of incorporated 18 O atoms resulted in the complete assignment of the labeled positions with accurate isotope ratios; the positions labeled from molecular oxygen ( 18 O 2 ) were O(1)/O(2), O(3), O(5), O(6), O(8), O(9), O(10), and O(12). Those labeled from [ 18 O 2 ]acetate were O(4), O(6), O(7), and O(11) (oxygen atoms are numbered beginning with those of carboxylic acid as O(1)/O(2) to O(13) in ring G). These incorporation patterns suggest that the cyclization of ether rings C, D, and E occurs via a β-epoxide intermediate at C22−C23, and the carboxylic acid is formed by Baeyer−Villiger oxidation.