Isoflavone derivatives

Red clover is a plant that contains isoflavones in a slightly different composition compared with soy. Red clover contains formononetin and biochanin A, which are not present in soy and may thus have additional biological activity. So far, four studies (Barber et ah, 1999 Knight et ah, 1999 van de Weijer, 2002 Tice et ah, 2003) have been performed using isoflavones derived from red clover (Table 4.3). These have used doses of isoflavones ranging from 40 to 160 mg. Three out of four of these studies did not show any effects, even in spite of a very large sample size (Tice et ah, 2003). Only one study showed a reduction in the number of hot flushes. The reduction, however, was small (van de Weijer and Barentsen, 2002). Red clover therefore does not appear to have much of an effect on the reduction of hot flushes. 

Effects of isolated isoflavones derived from red clover. 

Constantinou AI, Husband A. (2002) Phenoxodiol (2H-l-benzopyran-7-0,l,3-(4-hydroxyphenyl)), a novel isoflavone derivative, inhibits DNA topoisomerase II by stabilizing the cleavable complex. Anticancer Res 22 2581-2585. 

Constantinou AI, Mehta R, Husband A. (2003) Phenoxodiol, a novel isoflavone derivative, inhibits dimethylbenz[a]anthracene (DMBA)-induced mammary carcinogenesis in female Sprague-Dawley rats. Fur J Cancer 39 1012-1018. 

Gambacciani M, Ciaponi M, Cappagli B, Piaggesi L, Genazzani AR. Effects on combined low dose of the isoflavone derivative ipriflavone and estrogen replacement on bone mineral density and metabolism in postmenopausal women. Maturitas 28, 75-81, 1997. 

Mahabusarakam, W. et al., A benzil and isoflavone derivatives from Derris scandens Benth. Phytochemistry, 65, 1185, 2004. 

Maskey, R.P. et al., Flavones and new isoflavone derivatives from microorganisms isolation and structure elucidation, Zeitschrift fuer Naturforschung B, 58, 686, 2003. 

Rahman, M.M. et al.. New salicylic acid and isoflavone derivatives from Flemingia paniculata. Journal of Natural Products, 67, 402, 2004. 

Glycine max (L.) Merrill G. soja Sieb. Zucc. Da Dou Ye Da Dou (Soybean) (seed) Protein, isoflavone derivatives, genisteine, daidzein, riboflavin, thiamine, niacin, pantothenic acid, choline.33,67 Phytoestrogenic, elevate the vasomotor system, prevent cancer, a potent inhibitor of protein tyrosine kinase. 

The small particle size (4 pm) of the bonded phases and small pore size (60 A) of the Cl8 column efficiently resolve mixtures of similar isoflavone derivatives in the soy food matrix. 

Isoflavone derivatives along with nonvolatile components in soy sauce were also analyzed by gradient reversed-phase HPLC. This HPLC profile of soy sauce was further utilized by a pattern recognition program to understand the quality differences of soy sauces (132), and three isoflavone derivatives (esters of tartaric acid with daidzein, genistein, and 8-hydroxygenistein) were found to contribute significantly to the differentiation in fermented soy sauce. Fermented... 

E Kinoshita, Y Ozaw, T Aishima. Novel tartaric acid isoflavone derivatives that play key roles in differentiating Japanese soy sauce. J Agric Food Chem 45 3753-3759, 1997. 

Tamura, S., Chang, C., Suzuki, A., Kymai, S. Isolation and structure of a novel isoflavone derivative in red clover. Agri Biol Chem 1967 31 1108-1109. 

It was further discovered that 3-bromochromones readily react with arylboronic acids or their esters under the Suzuki coupling conditions to provide the corresponding isoflavone derivatives in excellent yields (Eq. (69)) [112]. 

Mass spectrometry was also helpful in determining the structure of the isoflavone derivative munetone.56... 

Kanaoka, S., Uesugi, T., Hirai, K., Toda, T., and Okuhira, T. 1998. Clathrate of isoflavone derivatives and edible composition comprising the same. US patent 5,847,108. 

Regarding the formation of these isoflavone derivatives, it is extremely interesting that some people are unable to produce equol or that they produce it in very low amounts. In fact, studies report that a third part of the general population cannot form equol. This demonstrates that the breakdown of isoflavones by the microflora in the gut determines the recovery of the compounds, and that the excretion to the urine of equol and other isoflavones derivatives, such as O-DMA, is dependent on the different composition of intestinal microflora. To confuse the issue even more, some researchers report that the production of isoflavone derivatives, such as equol, also depends on diet and gender a high fat/meat content diet increases equol production in women but not in men, which is explained by promotion of the growth or the activity of the bacterial populations responsible for equol production. On the other hand, no age-related differences for isoflavone metabolism have been reported [12, 13],... 

Soy phytoestrogens, especially isoflavone derivatives daid-zein and genistein, are nutritional factors that, among many other effects, may affect iodine utilization. 

In particular, the key intermediate product 381 in the synthesis of wighteone was prepared by the oxidative rearrangement of 3 -iodotetraalkoxychalcone 380 [474] and the key step in the synthesis of ( )-indatraline involved the HTIB-promoted diastereoselective ring contraction of a 1,2-dihydronaphthalene 382 to construct the indane ring system 383 (Scheme 3.152) [475]. A similar oxidative rearrangement of 3-cinnamoyl-4-hydroxy-6-methyl-2/7-pyran-2-ones with HTIB in dichloromethane followed by cycliza-tion was used by Prakash and coworkers for the direct conversion of o-hydroxychalcones into isoflavone derivatives [476]. 

This reaction was first reported by Allan and Robinson in 1924. It is the synthesis of fiavones or isoflavones derivatives by means of the condensation between o-hydroxyaryl ketones and an anhydride of aromatic acid in the presence of the sodium salt of corresponding acid in the anhydride. Thus this reaction is known as the Allan-Robinson condensation, Allan-Robinson s flavone synthesis, Allan-Robinson reaction, and Allan-Robinson synthesis. ... 

Many isoflavone derivatives are formed from precursors lacking the 5-hydroxyl group. Studies with C labeling confirm that loss of the hydroxyl group usually occurs before cyclization of the A ring (i.e., at the chalcone stage) (Dewick, 1984). The enzyme chalcone reductase coacts with chalcone synthase and NADPH as a cofactor in the formation of 4,2, 4 -trihydroxychalcone (Barz and Welle, 1992). 

Fig. 11.35. Representative isoflavone-derived phytoalexins from the Fabaceae,...

About 60 isoflavone derivatives that incorporate a prenyl group into the structure are insecticidal and piscicidal (Dewick, 1988 Harbome, 1991). Plants that contain rotenone (121) Derris and Lonchocarpus spp.) have long been used as natural insecticides and piscicides. These compounds are best known from the fabaceous genera Amorpha, Derris, Lonchocarpus, Milletia, Mundulea, and Tephrosia (Dewick, 1988 Harbome, 1991). 

Fig. 324. Structural formulas of some isoflavone-derived natural products...

The B-ring in isoflavones is phenolic and therefore similar to that in tyrosine (Figure 1). Accordingly, we hypodiesize that isoflavones react with ONOO, HOCl, and HOBr, thereby forming new isoflavone derivatives at the site of inflmnmation. These modifications to the isoflavones may alter their properties at specific receptor sites such as the estrogen receptors and in signal transduction pathways. 

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