Biosynthesis of halogenated marine natural

Butler A, Carter-Franklin JN (2004) The Role of Vanadium Bromoperoxidase in the Biosynthesis of Halogenated Marine Natural Products. Nat Prod Rep 21 180... 

Carter-Franklin JN, Butler A (2004) Vanadium Bromoperoxidase-Catalyzed Biosynthesis of Halogenated Marine Natural Products. J Am Chem Soc 126 15060... 

Butler, A. and J.N. Carter-Franklin. 2004. The role of vanadium peroxidase in the biosynthesis of halogenated marine natural products. Nat. Prod Rep. 21 180-188. 

Carter-Franklin, J.N. and Butler, A. (2004) Vanadium bromoperoxidase-catalyzed biosynthesis of halogenated marine natural products. J, Am, Chem, Soc 126,15060-15066. 

The final Learning Group Problem for this chapter asks you to propose a scheme for biosynthesis of the marine natural product kumepaloxane by electrophilic halogen addition. Kumepaloxane is a fish antifeedant synthesized by the Guam bubble snail Hami-noea cymbalum, presumably as a defense mechanism for the snail. In later chapters we shall see other examples of truly remarkable marine natural products, such as brevetoxin B, associated with deadly red tides, and eleutherobin, a promising anticancer agent. 

Of the more than 4500 known naturally occurring organohalogen compounds, a large fraction are alkaloids [1,3]. Most of these halogenated pyrroles, indoles, carbazoles, carbolines, tyrosines, and others have a marine origin. The present chapter surveys the occurrence, structure, and biosynthesis of these fascinating natural products. However, given their sheer number, this review focuses mainly on recent examples. 

The biosynthesis of certain halogenated marine natural products is intriguing. Some of their halogens appear to have been introduced as electrophiles rather than as Lewis bases or nucleophiles, which is their character when they are solutes in seawater. But how do marine organisms transform nucleophilic halide anions into electrophilic species for incorporation into their metabolites It happens that many marine organisms have enzymes called haloperoxidases that convert nucleophilic iodide, bromide, or chloride anions into electrophilic species that react like F, Br, or CF. In the biosynthetic schemes proposed for some halogenated natural products, positive halogen intermediates are attacked by electrons from the 77 bond of an alkene or alkyne in an addition reaction. 

The biosynthesis of organohalogens has seen enormous interest since the first survey, and several examples are mentioned earlier in the present review. Space does not allow for full coverage of this topic, but some additional examples are presented here. The reader is also directed to general reviews on the biosynthesis of marine natural products, many of which contain halogen (2398-2401), terrestrial fungal (basidiomycetes) metabolites (2402), and halogenated alkaloids (2403). 

Electrophilic aromatic halogenations occur in the biosynthesis of numerous naturally occurring molecules, particularly those produced by marine organisms. In humans, the best-known example occurs in the thyroid gland during the biosynthesis of thyroxine, a thyroid hormone involved in regulating growth and metabolism. The amino acid tyrosine is first iodinated by thyroid peroxidase, and two of the iodinated tyrosine molecules then couple. The... 

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