Epoxides from dialdehydes

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]...

Epoxides, The unstable epoxide (2) was prepared in 7 5 % yield from the dialdehyde (1) with Mark s reagent using appropriate care. The method had previously been reported to fail in this casc. ... 

The major aldehyde products of lipid peroxidation are malon-dialdehyde and 4-hydroxynonenal (Table 1, Fig. 4). Malondi-aldehyde can react with DNA to generate adducts at the bases A, C, and G. The mutagenic adduct MIG (pyrimido(l,2-a)purin-10(3H)one) has been detected at levels as high as 1 adduct per 10 nucleosides in human tissues. MIG is a reactive electrophile that can undergo further modification, leading to crosslinking of an adducted DNA strand to the opposite strand, or to some protein (22). Exocyclic etheno adducts can also arise from lipid peroxidation, possibly by reaction of an epoxide of 4-hydroxynonenal with A, C, or G in DNA. 

AFAR is highly induced by OPZ this enzyme, first purified from ethoxyquin-treated rat liver, has been shown to play a role in AFBl detoxication [75, 76], CYP-mediated AFBl-8,9-epoxides are mostly spontaneously hydrolyzed to AFBl-8,9-dihydrodiol (Fig. 3) that, under physiological conditions, can rearrange to form a reactive dialdehyde this metabolite does not bind to DNA but can react with primary amine groups in intracellular proteins [77]. AFAR catalyzes the NADPH-dependent reduction of AFBl-dialdehyde to AFBl-dialcohol, thereby reducing AFBl cytotoxicity [78, 79]. 

Lipid oxidation products can interact with proteins and amino acids, and can affect the flavor deterioration and nutritive value of food proteins. Peroxyl radicals are very reactive with labile amino acids (tryptophane, histidine, cysteine, cystine, methionine, lysine and tyrosine), undergoing decarboxylation, decarbonylation and deamination. Methionine is oxidized to a sulfoxide combined cysteine is converted to cystine to form combined thiosulfinate (Figure 11.4). Aldehydes, dialdehydes and epoxides derived from the decomposition of hydroperoxides react with amines to produce imino Schiff bases (R-CH=N-R ). Schiff bases polymerize by aldol condensation producing dimers... 

The photooxygenation of furans was investigated initially by Schenck in the mid-forties. A crystalline and highly explosive material 32 was isolated from the parent furan by Schenck and Koch. This secondary ozonide rearranges thermally to an epoxybutanolide and a fcis-epoxide reduction with triphenylphos-phine leads to maleic dialdehyde, methanolysis to a methoxy butenolide. 

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