Isoflavones reactions

The isoflavone 406 is prepared by the indirect a-phenylation of a ketone by reaction of phenylmercury(II) chloride with the enol acetate 405, prepared from 4-chromanone[371]. A simple synthesis of pterocarpin (409) has been achieved based on the oxypalladation of the oriho-mercurated phenol derivative 408 with the cyclic alkene 407[372,373]. 

Over the years there have many reports of isoflavone syntheses utilizing the K-R reaction. 

Synthesis and reactions of isoflavone analogs, 3-hetarylchromones 99KGS3. 

Unusual formation of isoflavone 304 during reaction of 302 is explained by equilibrium between 302 and its enol form 303, which is able to undergo denitro-cyclization reaction to the isoflavone (Scheme 46) (81UC(B)495, 81UC(B)1094). The other product 305 is formed by a different type of participation of the ortho-mlTO group combined with a deformylation. For a review on this type of reaction, see (72CR627). 

Isoflavones have been implicated in goiter induction. Soybean extracts inhibit reactions catalyzed by thyroid peroxidase (TPO), essential to the synthesis of thyroid hormones (Divi et al., 1997). Genistein and daidzein (at about 1-10 p,M of IC50) may act as alternative substrates for tyrosine iodination (Divi et al., 1997). Furthermore, genistein and daidzein have also been shown to cause the irreversible inactivation of TPO in the presence of hydrogen peroxide. Genistein also inhibits thyroxine synthesis in the presence of iodinated... 

COWARD L, KIRK M, ALBIN N and BARNES s (1996) Analysis of plasma isoflavones by reversed-phase HPLC-multiple reaction ion monitoring-mass spectrometry. Clin Chim Acta. 247 (1-2) 121-42. 

WEI H, CAO Q AND RAHN R o (1996) Inhibition of UV light- and Fenton reaction-induced oxidative DNA damage by the soybean isoflavone genistein. Carcinogenesis. 17 (1) 73-7. 

The possible pathways for the transformations 323 -> 324 and 323 - 325 are outlined in Scheme 84. The first step that is common to these reactions involves the electrophilic attack of the I(III) species on the enol form of 323 at the face of the molecule anti to the C(2)-aryl ring to provide intermediate 328. Routes (a) and (a ) involving a 1,2-aryl shift lead to isoflavones 324. Route (b), involving Sn2 attack of X /XH at the C(3)-position of intermediate 328, leads to 325 via 329. The nucleophilicity of X XH plays a deciding role in affecting the course of the reaction. 

Koch-Haaf reaction, 17, 3 Kornblum oxidation, 39, 3 Kostaneki synthesis of chromanes, flavones, and isoflavones, 8, 3... 

Functionalized isoflavones can be easily obtained from the cross-coupling reaction of 3-iodochromones with Ar3Bi under Pd catalysis (Scheme 44). The coupling reaction of a variety of substituted 3-iodochromones and Ar3Bi afforded substituted isoflavones in high yields [60]. 

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. 

Drewes, S.E. et al.. Minor pyrano-isoflavones from Eriosema kraussianum activity-, structure-, and chemical reaction studies. Phytochemistry, 65, 1955, 2004. 

Enone formation-aromatization has been used for the synthesis of 7-hydro-xyalkavinone (716)[456], The isoflavone 717 was prepared by the elimina-tion[457]. The unsaturated j-keto allyl esters 718 and 719. obtained in two steps from myreene. were subjected to enone formation. The reaction can be carried out even at room temperature using dinitriles such as adiponitrile (720) or 1,6-dicyanohexanc as a solvent and a weak ligand to give the pseudo-ionone isomers 721 and 722 without giving an allylated product(458]. 

Under normal reaction conditions (heating the reactants with or without a solvent in an alkaline medium) the pyranone ring of chromones, flavones and isoflavones is opened at... 

Pyran-4-ones and their monobenzo derivatives undergo ring opening when treated with aqueous alkali. This reaction has been widely used in the investigation of structure of chromones, flavones and isoflavones but xanthones are little affected. The nucleophile attacks the 1,2-bond in a rate-determining step whose rate constant varies with the electron density in the ground state at C-2. A kinetic study of the reaction with several chromones supports the mechanism shown in Scheme 25 (79ACH(101)73). 

Other examples include the formation of 3-acetyl-2-methoxychromene from 4-methoxybut-3-en-2-one (80MI22400) and 2-morpholino-3-phenylchromene (93) from AC-styrylmorpholine (81TL2113, 82JCS(pl)l 193). The latter is surprising in view of the earlier report that this reaction affords an isoflavone via the alcohol (66JOC1232). It seems likely that the alcohol is dehydrated under the experimental conditions. 

Several groups have described syntheses of chromones which involve the use of enamines. Reaction of salicylaldehyde with 1-morpholinocyclohexene gives the chromanol which is readily oxidized to the chromone (66JOC1232). Other examples include the use of 1-morpholino-l-phenylethylene which gives flavene, whilst N-styrylmorpholine yields isoflavone. The enamine reaction is considered to proceed in the normal manner with subsequent cyclization involving the neighbouring phenolic group (Scheme 163). 

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. 

Sato et a2- (34) demonstrated that a variety of common meat additives, inclucnrTg cottonseed flour, nonfat dry milk, spray-dried whey, wheat germ, and textured soy flour, inhibited WOF in the meat system. These products may have exerted their inhibitory effect on WOF through the Maillard reaction, since most of them contain some reducing sugars. Pratt (40) reported soybeans and soy protein concentrate had an inhibitory effect upon development of WOF and was able to demonstrate that the active components are water soluble. Fractionation and analysis of the water-soluble fraction showed the antioxidant activity was due to the presence of isoflavones and hydroxylated cinnamic acids (40). This confirms earlier work showing that the flavonoTcis present in plant extracts inhibit oxidation in sliced roast beef (41 ). 

Similar intermediates might be involved in the rearrangement of chalcones 83 by [bis(trifluoroacetoxy)iodo]benzene 4 in refluxing methanol. Compounds of type 84 can be obtained, Scheme 36, which have been employed in the synthesis of isoflavones. The yield of this reaction is dependent on the electron density of the aromatic moieties [144]. 

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