Aflatoxins structures

Consideration of the generalized aflatoxin structure represented in (I) leads one to the inescapable conclusion that at the core of the system is the A-ring in the form of a phloroglucinol nucleus, in which each of the pendant phenolic oxygen atoms is uniquely differentiated. Furthermore, two of the three carbon sites on this nucleus are differentially substitued with carbon moieties. This constitutes a potentially difficult synthetic circumstance in that not only must a high degree of substitution be provided for, but also a certain amount of regiochemical control must... 

Also used as a spectral comparison model for the elucidation of the B and G aflato-xinsss this compound was prepared in a multi-step synthesis. The von Pechmann condensation of phloroglucinol dimethyl ether (59)133 with diethyl cyclopentane-4,5-dione-l, 3-dicarboxylate (41) in acidic solution afforded the /J-ketoester (42), which readily underwent decarboalkoxylation, in a seperate step, to give the keto-coumarin (5). The beauty of this methodology is illustrated by the use of the symmetrical diketoester (41), which of course, only allows for the formation of a single coumarin (von Pechmann) product (42). The regiochemistry of the final product, however, was demonstrated to be the incorrect isomer insofar as the aflatoxin structures were concerned. 

Ayres, J.L., D.J. Lee, J.H. Wales and R.O. Sinnhuber. Aflatoxin structure and hepatocarcinogenicity in rainbow trout (Salmo gairdneri). J. Natl. Cancer Inst. 46 561-564, 1971. 

It is of interest to compare the shapes and sizes of various molecules with appreciable carcinogenic activity. For example, aflatoxin B] (VI), found in moldy peanuts and grain, is one of the most powerful carcinogens known. Its crystal structure was determined by van Soest and Peerdeman (46-48). 

Fig. 10.30. Structure of aflatoxin B1 exo-8,9-epoxide (10.132), the dihydrodiol resulting from hydrolysis (10.133), and the reactive a-hydroxy dialdehyde (10.134) that exists in equilibrium with the diol under alkaline conditions [204]...

In the pH range of 5 - 10, H20-catalyzed hydrolysis is the predominant mechanism (see Fig. 10.11, Pathway b), resulting in the formation of the (8R,9R)-dihydrodiol (10.133, Fig. 10.30). Thus, aflatoxin B1 exo-8,9-epoxide is possibly the most reactive oxirane of biological relevance. Such an extreme reactivity is mostly due to the electronic influence of 0(7), as also influenced by stereolectronic factors, i.e., the difference between the exo- and endo-epoxides. The structural and mechanistic analogies with the dihydro-diol epoxides of polycyclic aromatic hydrocarbons (Sect. 10.4.4) are worth noting. 

A Large molecular weight compounds of diverse structures Erythromycin Gestodene Synthetic steroids Aflatoxin Bj, senecionine... 

Aflatoxins B are fungal metabolites and are produced by Aspergillus flavus. There are several related products all contain a phloroglucinol segment in their structure and all are extremely toxic and carcinogenic, eg, aflatoxin B (56) (201). 

The most common source of aflatoxins is moldy food, particularly nuts, some cereal grains, and oil seeds. The most notorious of the aflatoxins is aflatoxin B1( for which the structural formula is shown in Figure 19.1. Produced by Aspergillus niger, it is a potent liver toxin and liver carcinogen in some species. It is metabolized in the liver to an epoxide (see Section 7.3). The product is electrophilic with a strong tendency to bond covalently to protein, DNA, and RNA. Other common aflatoxins produced by molds are those designated by the letters B2, G1( G2, and M,. 

Wogan. Structural identification of the major ENA adduct formed by aflatoxin Bj in vitro. Proc. Natl. Acad. Sci. U.S.A. 74 1870-1874, 1977. 

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