Isoflavones, formation

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). 

Table 6.6 Effect of isoflavones in cellular models of bone formation...

Authors Cell model of bone formation Effect of isoflavones... 

An efficient synthesis of flavones, which occurs without formation of the corresponding aurone, involves the carbonylative cyclisation of oacetoxyiodophenols and arylalkynes (Scheme 48) . A large scale, one-pot synthesis of isoflavones has been described <00SC469>. 

LI. Labow, R. S., and Layne, D. S., The formation of glucosides of isoflavones and of some other phenols by rabbit liver microsomal fractions. Biochem. J. 128, 491-497 (1972). 

A similar route to 3-substituted chromones and isoflavone (R = Ph) Scheme 5.10 relies upon a Claisen-Hke condensation between the enolate of a 2-hydroxyphenyl ketone and ethyl formate (methanoate) (Scheme 5.11). 

Isoflavones Trifolium pretense MeOH-10 mM ammonium formate buffer, pH 4.0 APCI(+) IT and Q 364... 

MALDI-TOF-MS has been used to identify and quantify other anthocyanins in foods.When the anthocyanin content of highbush blueberries at different stages of anthocyanin formation were analyzed by both HPLC and MALDI-TOF-MS, it was found that both techniques provided comparable quantitative anthocyanin profiles. While HPLC could distinguish anthocyanin isomers, MALDI-TOF-MS proved to be more rapid. MALDI-TOF-MS has also been used to identify the isoflavones in soy samples. In a comparison of several matrices, 2, 4, 6 -trihydroxyacetophenone (THAP) and 2,5-dihydroxybenzoic acid... 

The formation of phytoalexins such as glyceollins and phaseollins requires C-prenylation by a range of pterocarpan prenyltransferase (PTP) activities, with dimethylallyl pyrophosphate (DMAPP) as the prenyl donor. For glyceollins and phaseollins, prenylation occurs at position C-2 or C-4 of glycinol or C-10 of 3,9-dihydroxypterocarpan. ° ° However, there are differing activities in other species. For example, in Lupinus albus (white lupin) a prenyltransferase acting at the C-6, -8, and -3 positions of isoflavones has been identified.PTPs have also been characterized in detail for the formation of prenylated flavanones in Sophora flavescens (see, e.g., Ref. 207). However, no cDNA clones for flavonoid-related prenyltransferases have been published to date. 

Consumption of soy foods (providing 60mg/day isoflavones) for 12 weeks by postmenopausal women has been found to significantly decrease clinical risk factors for osteoporosis (short-term markers of bone turnover) including decreased urinary M-telopeptide excretion (bone resorption marker) and increased serum osteocalcin (bone formation marker). Furthermore, consumption of a soy isoflavone supplement containing 61.8 mg of isoflavones for 4 weeks by postmenopausal Japanese women significantly decreased excretion of bone resorption markers. ... 

A study in 500 Australian women (aged 40 to 80 years) has shown that higher isoflavone intakes are associated with higher concentrations of bone alkaline phosphatase, a short-term marker of bone formation and turnover. 

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]. 

Chromones are readily oxidized by permanganate or dichromate with opening of the pyran ring and the formation of a salicylic acid (402). Flavones and isoflavones are also degradatively oxidized for example oxidation of munetone (403) with alkaline hydrogen peroxide yields 2-methoxybenzoic acid and 4-hydroxy-2-isopropylbenzofuran-5-carboxylic (isotubaic) acid. 

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. 

The same one-carbon unit has been employed in a convenient isoflavone synthesis from deoxybenzoins (76S326). Other methods of ring closure of phenyl benzyl ketones to this heterocycle have been reviewed (B-62MI22400) and include triethyl orthoformate (56PIA(A)(44)36), zinc cyanide (58CB2858), ethyl formate (80BCJ831) and ethoxalyl chloride (70JCS(C)1219). 

Hinderer W, Flentje U, Barz W. 1987. Microsomal isoflavone 2- and 3-hydroxylases from chickpea (Cicer arietinum L.) cell suspensions induced for pterocarpan phytoalexin formation. FEBS Lett 214 101-106. 

Liu C-J, Dixon RA. 2001. Elicitor-induced association of isoflavone O-methyltransfer-ase with endomembranes prevents the formation and 7-O-methylation of daidzein during isoflavonoid phytoalexin biosynthesis. Plant Cell 13 2643-2658. 

The reactions of arylation of heterocyclic /3-ketoesters were employed in the synthesis of a number of isoflavanones and isoflavones.27,28 cr-Methylene cr-arylketones can be easily and selectively obtained by arylation of allyl /3-ketoesters which are eventually deprotected by the Tsuji s procedures. a Deallyloxycarbonylation was performed by treatment of the allyl cr-aryl-/3-ketoesters with catalytic amounts of palladium(n) acetate, triethylammo-nium formate and triphenylphosphane in THF at room temperature and afforded the a-arylketones in 75-97% yield.27 Deallyloxycarbonylation-dehydrogenation can be realized with the same allyl esters by treatment with catalytic amounts of palladium(n) acetate and l,2-bis(diphenylphosphino)ethane (DPPE) in acetonitrile under reflux and affords the ct-aryl cr,/3-unsaturated ketones in 60-90% yield (Scheme 4).28 In particular, this reaction was used in a direct convergent synthesis of 2 -hydroxyisoflavones involving arylation of an appropriate allyl /3-ketoester with the MOM-protected (2-methoxymethoxyphenyl)lead triacetate derivative (Scheme 4). The reaction of the isomeric... 

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