Natural products halogenation

Gopichand, Y., F.J. Schmitz, J. Shelly, A. Rahman, and D. van der Helm Marine Natural Products Halogenated Acetylenic Ethers from the Sea Hare Aplysia dactylomela. J. Org. Chem. 46, 5192 (1981). 

Derivatives of the natural product juglone [77189-69-6] eg (109), have been obtained ia 90% yield ia a single reaction involving halogenation and oxidation by A/-bromosucciniinide (115). 

Potable Water Treatment. Treatment of drinking water accounts for about 24% of the total activated carbon used in Hquid-phase apphcations (74). Rivers, lakes, and groundwater from weUs, the most common drinking water sources, are often contaminated with bacteria, vimses, natural vegetation decay products, halogenated materials, and volatile organic compounds. Normal water disinfection and filtration treatment steps remove or destroy the bulk of these materials (75). However, treatment by activated carbon is an important additional step in many plants to remove toxic and other organic materials (76—78) for safety and palatability. 

The Suzuki reaction has proved extremely versatile and has found extensive use in natural product. synthesis. " Arylboronic acids [ArB(OH)2 are the usual substrates in this reaction together with arylhalides or triflates (Ar X, X = halogen... 

The activity of PK and NRPSs is often precluded and/or followed by actions upon the natural products by modifying enzymes. There exists a first level of diversity in which the monomers for respective synthases must be created. For instance, in the case of many NRPs, noncanonical amino acids must be biosynthesized by a series of enzymes found within the biosynthetic gene cluster in order for the peptides to be available for elongation by the NRPS. A second level of molecular diversity comes into play via post-synthase modification. Examples of these activities include macrocyclization, heterocyclization, aromatization, methylation, oxidation, reduction, halogenation, and glycosylation. Finally, a third level of diversity can occur in which molecules from disparate secondary metabolic pathways may interact, such as the modification of a natural product by an isoprenoid oligomer. Here, we will cover only a small subsection of... 

Figure 13.17) [56], It is believed that a variety ofhalogenations proceed via this mechanism for electron-deficient molecules [57,58]. It is yet to be determined if the halogenation can take place on substrates which are not covalently linked to natural product synthases. 

Galonic, P.D., Vaillancourt, FH. and Walsh, C.T. (2006) Halogenation of unactivated carbon centers in natural product biosynthesis trichlorination of leucine during barbamide biosynthesis. Journal of the American Chemical Society, 128, 3900-3901. 

In the biosynthetic schemes proposed for some halogenated natural products, positive halogen intermediates are attacked by electrons from the n bond of an alkene or alkyne in an addition reaction. 

While common biosynthetic pathways may provide the framework for the various classes of secondary metabolites, their functionality is imparted by specialized tailoring enzymes that are often unique to natural products (Walsh 2004 Hertweck et al. 2007). Whether it is the addition of alcohol groups, halogenation (Gribble 1998), oxidation, reduction, stereochemical manipulation, or cyclization, it is often these functionalities that make secondary metabolites unique and bioactive. 

Sims JJ, Lin GHY, Wing RM (1974) Marine natural products. X. Elatol, a halogenated sesquiterpene alcohol from the red alga Laurencia elata. Tetrahedron Lett 39 3487-3490 Singh S, Kate BN, Banerjee UC (2005) Bioactive compounds from cyanobacteria and microalgae an overview. Crit Rev Biotechnol 25 73-95... 

Laturnus F, Wiencke C, Kloser H (1996) Antarctic macroalgae - sources of volatile halogenated organic compounds. Mar Environ Res 41 169-181 Lebar ML, Heimbegner JL, Baker BJ (2007) Cold-water marine natural products. Nat Prod Rep 24 774-797... 

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. 

Chlorinated micropoUutants are harmful for man and environment due to their toxicity, persistence, and bioaccumulation. Persistent compounds are very stable and difficult to get metabolized and mineralized by biological and chemical processes in the environment, and as a result, they have become ubiquitous in water, sediments, and the atmosphere bioaccumulation is the result of the lipophilicity of these compounds. Polychlorinated dibenzodioxins and -furans (PCDD/F) are not produced purposely like many of other chlorinated technical products, such as chlorinated biocides DDT, lindane, and toxaphene. The production and use of persistent organic pollutants (POPs), the dirty dozen has now been banned worldwide by the Stockholm protocol. It should be mentioned that about 3000 halogenated products have now been isolated as natural products in plants, microorganisms, and animals," but the total amount of these products is much smaller compared to xenobiotics. 

Peroxidases have been used very frequently during the last ten years as biocatalysts in asymmetric synthesis. The transformation of a broad spectrum of substrates by these enzymes leads to valuable compounds for the asymmetric synthesis of natural products and biologically active molecules. Peroxidases catalyze regioselective hydroxylation of phenols and halogenation of olefins. Furthermore, they catalyze the epoxidation of olefins and the sulfoxidation of alkyl aryl sulfides in high enantioselectivities, as well as the asymmetric reduction of racemic hydroperoxides. The less selective oxidative coupHng of various phenols and aromatic amines by peroxidases provides a convenient access to dimeric, oligomeric and polymeric products for industrial applications. 

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