Nitration, isoflavones

Black cohosh may cause nausea, vomiting, hypotension, and even miscarriage. It is absolutely contraindicated in pregnancy. Red clover contains coumarins and should therefore be avoided with anticoagulants. Diets high in red clover isoflavones have reduced livestock fertility and theoretically could do the same in humans. Flaxseed may cause nausea, diarrhea, and flatulence. Cyanogenic nitrates in flax (especially in immature seed pods) have produced toxic reactions. 

D Alessandro T, Prasain J, Benton MR et al. Polyphenols, inflammatory response, and cancer prevention chlorination of isoflavones by human neutrophils. J. Nutr. 133, 3773S-3777S, 2003. Boersma BJ, D Alessandro T, Benton MR et al. Neutrophil myeloperoxidase chlorinates and nitrates soy isoflavones and enhances their antioxidant properties. Free Radical Biol. Med. 35, 1417-1430, 2003. 

Protection of the 2 -hydroxy group is not necessary when thallium(III) nitrate is used <74JCS(Pl)305). The reaction is also much faster and this technique appears to be the one of choice, especially for the synthesis of naturally occurring isoflavones (75CB3883). 

Evidence has been presented that 2-hydroxychalcones are also transformed into flavones on reaction with thallium(III) nitrate (equation 16) (78TL3359). Such a method would be complementary to the isoflavone synthesis if it proves to be of general applicability. 

Figure 4.5 Sites of tissue modification of isoflavones. In the A-ring, chlorination and hydroxy-lation occur at the 6- and 8-positions. In the B-ring, hydroxylation and nitration occur at the 3 -position.

Racemic homopterocarpin has been synthesised (ref. 107) from a chalcone obtained by the condensation of 2-hydroxy-4-methoxyacetophenone with 2,4-dibenzyloxybenzaldehyde. Conversion to an isoflavone with thallium (III) nitrate was followed by hydrogenation to generate the racemic furanochroman (C)in low yield together with two other products (A) and (B). Chromatographic separation of (C) and methylation afforded the final product as shown in Scheme 30. 

It is of interest to note in passing that In more recent work (ref.72), use has been made in synthesis of the transformation of chalcones to isoflavones with thallium(lll) nitrate. Thus, 6-acetyl-2,2-dimethyl-7-hydroxy-5-methoxychromanone was converted to the chalcone with 2,4-dibenzyloxybenzaldehyde. The O-acetyl derivative by treatment with the thallium reagent followed by acidic cyclisation gave a bischromanone structure. Selective reduction of the least hindered carbonyl group in the bischromanone, acidic dehydration of the resultant alcohol and final debenzylation with boron trichloride gave the linear isofiavone. 

Boersma BJ, Patel RP, Kirk M, Darley-Usmar VM, Barnes S. Chlorination and nitration of soy isoflavones. Arch Biochem Biophys 1999 368 265-275. 

In studies of the chemistry of compounds of this class it was shown that treatment of the chalcone (60) with thallium(iii) nitrate gave the isoflavone (61).i<">... 

Substitution reactions may serve an antioxidant function. Halogenation and nitration of isoflavones is discussed later in this volume. These reactions imply that the proinflamitory oxidants (hypobromous acid, hypochlorous acid, and peroxynitrite) might be reduced or moderated by reaction with isoflavones in vivo. 

Isoflavones have been shown to be beneficial in several chronic diseases in which oxidants are involved. Isoflavones are weak antioxidants when tested in vitro in die context of scavenging lipid peroxyl radicals. However, at sites of mflammation proinflammatory oxidants such as peroxynitrite (ONOO"), hypochlorous acid (HOCl), and hypobromous acid (HOBr) are formed that may also react widi isoflavones. We present evidence herein, using reverse-phase HPLC-mass spectrometry and proton NMR, that at concmitrations of diese oxidants formed at these local sites, nitration, chlorination, and bromination of isoflavones occurs. 

In die present study we have shown that the isoflavones can react with proinflammatory oxidants to form novel derivatives. By using LC-MS we have confirmed that isoflavones react widi HOBr to form mono- and dibrominated derivatives. These results correlate to the chlorination and nitration of die isoflavones our laboratory previously reported (20). Mono- and dichlorinated isoflavones were formed when reacted widi HOCl. Nitration of die isoflavcmes also occurs when reacted with ONOO. Nitration occurs at die C3 site of B-ring of the molecule. 

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