LABELING PATTERN OF OKADAIC ACID FROM O-18(2) AND [O-18(2)]ACETATE ELUCIDATED BY COLLISION-INDUCED DISSOCIATION TANDEM MASS-SPECTROMETRY

Okadaic acid (1) is a polyether compound produced by the marine dinofl agellate Prorocentrum lima. Its biosynthesis attracts considerable att ention since the carbon skeleton has been shown to be synthesized via an unusual route. However, a very limited amount of information is ava ilable for the formation of its ether rings. We applied collision-indu ced dissociation tandem mass spectrometry (CID MS/MS) to the elucidati on of the O-18-incorporation pattern of okadaic acid. The extensive de termination of O-18/O-16 ratios for each product ion bearing differing numbers of incorporated O-18 atoms resulted in the complete assignmen t of the labeled positions with accurate isotope ratios; the positions labeled from molecular oxygen (O-18(2)) were O(1)/O(2), O(3), O(5), O (6), O(8), O(9), O(10), and O(12). Those labeled from [O-18(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 beta-epoxide intermediate at C22-C23, and the c arboxylic acid is formed by Baeyer-Villiger oxidation.