Halogenated bipyrroles

Halogenated bipyrroles bioaccumulated in the marine food web. Source From Teuton, E. L., et al. 

Although few in number, halogenated bipyrroles represent one of the most interesting and potentially important classes of natural organohalogens yet to be discovered. Like DDT, PCBs, and other anthropogenic organochlorine compounds, some halogenated bipyrroles seem to bioaccumulate up the food chain and at least one is found in humans. 

The first example of a halogenated bipyrrole was the marine bacterium Chromobacterium sp. metabolite 35 <74MB281>. Both nudibranchs (sea slugs) and bryozoans (moss animals) secrete brominated bipyrroles ("tambjamines") as chemical defensive agents. Some recent examples from the bryozoan Bugula dentata are tambjamines G-J (36-39) <94AJC1625>. 

The pyrrole ring is widely distributed in nature. It occurs in both terrestrial and marine plants and animals [1-3]. Examples of simple pyrroles include the Pseudomonas metabolite pyrrolnitrin, a recently discovered seabird hexahalogenated bipyrrole [4], and an ant trail pheromone. An illustration of the abundant complex natural pyrroles is konbu acidin A, a sponge metabolite that inhibits cyclin-dependent kinase 4. The enormous reactivity of pyrrole in electrophilic substitution reactions explains the occurrence of more than 100 naturally occurring halogenated pyrroles [2, 3]. 

Although V-protected 2-lithiopyrroles are readily generated and many types are known [6, 26], these intermediates have not generally been employed to synthesize halogenated pyrroles. One exception is the synthesis of the two natural seabird hexahalogenated bipyrroles 15 and 17,... 

S., Vatter, S., Chahbane, N., Lenoir, D., Schramm, K.W. and Scherer, G. (2005) Biological activity and physicochemical parameters of marine halogenated natural products 2,3,3, 4,4, 5,5 -heptachloro-l -methyl-1,2 -bipyrrole and 2,4,6-tribromoanisole. Archives of Environmental Contamination and Toxicology, 48, 1-9. 

Surprisingly, many halogenated compoimds thought to be structurally similar to pollutants have been foimd to be naturally bioaccumulating in marine fish, birds, and mammals. These include the highly brominated bipyrroles (Figure 22.29). They are likely bacterial metabolites that are being passed up the food chain. 

Tittlemier SA, Fisk AT, Hobson KA, Norstrom RJ (2002) Examination of the Bioaccumulation of Halogenated Dimethyl Bipyrroles in an Arctic Marine Food Web Using Stable Nitrogen Isotope Analysis. Environ Pollut 116 85... 

Tittlemier S, Borrell A, Duffe J, Duignan PJ, Fair P, Hall A, HoekstraP, Kovacs KM, Krahn MM, Lebeuf M, Lydersen C, Muir D, O Hara T, Olsson M, Pranschke J, Ross P, Siebert U, Stem G, Tanabe S, Norstrom R (2002) Global Distribution of Halogenated Dimethyl Bipyrroles in Marine Mammal Blubber. Arch Environ Contam Toxicol 43 244... 

Vetter W, Jun W, Althoff G (2003) Non-Polar Halogenated Natural Products Bioaccumulated in Marine Samples. I. 2,3,3 ,4,4 ,5,5 -Heptachloro-l -methyl-l,2 -bipyrrole (Ql). Chemosphere 52 415... 

Tittlemier SA. Dietary exposure to a group of naturally produced organohalogens (halogenated dimethyl bipyrroles) via consumption of fish and seafood. J Agric Food Chem 2004 52 2010-5. 

In the past 10 years halogenated 1 -methyl-1,2 -bipyrroles (MBPs) 337 and 338 emerged as a class of naturally occurring compounds that have been isolated from marine samples. Their distribution pattern suggests biomagnification (09EST122). Achiral GC analysis was performed on various polyhalogenated samples (bromine and chlorine). 

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