Isoflavone, hydroxy derivatives

Isoflavones are derivatives of the parent compound isoflavone (3-phenylc,hromone 3-phenylbenzopyran-4-one). The dietary isoflavone phytoestrogens (notably from soya bean) that bind to the oestrogen receptor are the best known, namely daidzein (7,4 -dihydroxy-isoflavone), genistein (5,7,4 -trihydroxyisoflavone) and glycitein (7-hydroxy-6-methoxy-isoflavone) and their respective pro-phytoestrogen 7-0-glucoside precursors daidzin,... 

In chromones, the favoured sites for sulfonation are 6- and 8- positions which are respectively para and adjacent to the electron-donating hetero oxygen atom. Table 2 lists substituted chromones that have been sulfonated by treatment with chlorosulfonic acid. The 5-hydroxychromones were more easily sulfonated than the corresponding 7-hydroxy derivatives and when sulfonation of 5-methoxy-2-methylchromone was attempted under more drastic conditions than those reported here, the sulfonation was accompanied by demethylation of the substrate. Flavones and isoflavones are 2- and 3-phenylchromones (116 and 117) respectively. 

Reduction of coumarins to the dihydro-derivatives has frequently been achieved, but a more efficient procedure has emerged from a new study of this conversion. The most effective method was catalytic reduction in ethanol at 150 °C and under a high pressure (1500 psi) of hydrogen of give mostly the 2-hydroxy-3-phenylbutanoate, which was readily cyclized with PPA to the dihydrocoumarin. Hydroboration of 3-arylcoumarins, followed by oxidation, gave isoflavanones the latter have been dehydrogenated (with DDQ) to isoflavones. A reaction of wide potential value is the selective hydrolysis by zinc and methanol of phenolic acetates in the presence of aUphatic acetate groups. 

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. 

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]. 

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