MXPA01008233A - Production of isoflavone derivatives - Google Patents

Abstract

Methods for the hydrogenation of isoflavones are described which provide access to workable quantities of isoflavan-4-ols, isoflav-3-enes, and isoflavans. The isoflavone derivatives can be obtained in high purity and in near quantitative yields whilst employing pharmaceutically acceptable reagents and solvents.

Description

PRODUCTION OF DERIVATIVES OF ISOFLAVONA INTRODUCTION The present invention relates to the hydrogenation of isoflavones and the products thereof. The invention also relates to the synthesis of phytoestrogenic isoflavone metabolites and derivatives of isoflavone hydrogenation products.

BACKGROUND OF THE INVENTION The metabolites of isoflavone have a wide range of important biological properties, including estrogenic effects (WO 98/08503). The isoflavone metabolites can be isolated from the urine of human volunteers subjected to diets rich in vegetable isoflavonoids such as soybeans, lentils, peas and beans. Despite the newly discovered biological importance of isoflavone metabolites, there is currently no general method suitable for the large-scale synthesis of these metabolites. The few reported syntheses of these metabolites use either catalytic hydrogenation or reduction by hydrogen transfer of the corresponding isoflavones. These reduction reactions are found to be non-selective, extremely difficult to control and lead to different product mixtures.

It has been reported that the reduction of 5,7-dihydroxyisoflavylium salts provides mixtures of isoflav-2-enos, isoflav-3-enos and isoflávanos. Individual compounds are difficult to separate and can be obtained only with low yields. The reductions with sodium borohydride of isoflavones are known, see Ádám Major et al. Li ebigs Ann. Chem. (1988) 555-558, however the reactions are low yield, typically not clean, and substituents on the basic isoflavone ring structure require tedious protective groups unaffected by metal hydrides. Chromatography is often required to separate the reaction products and only low yields of isoflavanones, isoflavan-4-ols, isoflavanos and isoflavans are obtained. The required chromatography is tedious and often can not be practiced for large-scale reactions. In addition, attempts to improve the yield and purity of products obtained from hydrogenation have been met with limited success as is evident from published results that are quite contradictory. The solvents used in the hydrogenation reactions of the isoflavones reported in the literature include N-methyl lpyrrolidinone, see Liepa, A. J., Aus t. J. Chem. , 1981, 34, 2647-55. Without However, this solvent is not suitable for the pharmaceutical preparations of isoflavone metabolites and derivatives because jV-methylpyrrolidinone is a severe eye irritant and a possible carcinogen. In addition, the high melting point of the solvent makes it extremely difficult to remove after reduction. Isoflavan-4-ols are key intermediates in the synthesis of isoflavenos and therefore there is a need for a more efficient and reliable synthesis of isoflavan-4-ols, or at least comparable alternatives to those known in the art. There is also a need for synthetic methods for the hydrogenation of isoflavone using pharmaceutically more acceptable solvents than those reported above. Therefore, it is an object of the present invention to overcome or at least alleviate one or more of the aforementioned disadvantages of the prior art. Another objective of the present invention is to synthesize novel metabolites and isoflavone derivatives. Surprisingly, the inventors of the present have found hydrogenation conditions that allow the synthesis of isoflavone derivatives in good to excellent yields. In particular, the conditions found by the inventors herein allow hydrogenation of isoflavones for relatively pure tetrahydroisoflavan-4-ol products in excellent yields and without the need for pharmaceutically unsuitable solvents and extensive chromatography in hydrogenation reactions.

SUMMARY OF THE INVENTION Thus, the present invention provides a method for the hydrogenation of a compound of the formula I wherein Ri, R2, R3, R4, R5, R6, R and Rs are independently hydrogen, hydroxy, OR9, OC (O) Rg, 0S (0) R9, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, and R9 is alkyl, haloalkyl, aryl, arylalkyl or alkylaryl, to prepare a compound of formula II wherein Ri, R2, R3, R4, R5, R6, R7, s and R9 are as defined above. The present invention also provides a method for the dehydration of a compound of formula II, which method may optionally include deprotection or transformation steps, to prepare a compound of formula III where Ri / - R2i R3r - R5A Rd / R? and Rs are independently hydrogen, hydroxy, 0R9, OC (0) R9, OS (O) R9, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, and R9 is alkyl, haloalkyl , aryl, arylalkyl or alkylaryl, The present invention also provides a method for the hydrogenation of a compound of the formula I to prepare a compound of the formula IV wherein Ri / R2 R3 R4 / Rs / R3 / 7, Rs and R9 are as defined above. The present invention also provides a method for the hydrogenation of a compound of the formula III to prepare a compound of the formula V wherein i 2, 3r R 4 / R 5 / R 7 7 s and R 9 are as defined above. The present invention also provides the compounds of the formulas II, III, IV and V when prepared by a method described above and the compositions comprising the same. The present invention also provides novel compounds of the formulas I, II, III, IV and V and the compositions comprising the same.

DETAILED DESCRIPTION OF THE INVENTION In the methods of the present invention, the starting isoflavone of the formula I, the hydrogenation products isoflavan-4-ol of the formula II, the isoflavanone of the formula IV and the isoflavan of the Formula V and the product for isoflav-3-ene dehydration of the formula III preferably have the following substituents wherein Ri / 2/3 4/5 / ß R7 and Rs are independently hydrogen, hydroxy, ORg, 0C (0) R9, OS (O) Rg, alkyl, aryl, arylalkyl, thio, alkylthio, bromo, chloro or fluoro, and R9 is alkyl, fluoroalkyl or arylalkyl; more preferably have the following substituents wherein Ri is hydroxy, OR 9 or OC (0) R 9, R 2 / R 3 4 R 5 R 7 and R 7 are independently hydrogen, hydroxy, ORg, OC (O) R 9, alkyl, aryl or arylalkyl, R 8 is hydrogen, and Rg is methyl, ethyl, propyl, isopropyl or trifluoromethyl; and most preferably have the following substituents wherein Rx is hydroxy, ORg or OC (0) R9, R2 R3 R < j / 5 and R7 are independently hydrogen, hydroxy, ORg, 0C (0) Rg, alkyl, aryl or arylalkyl, Re and Rs are hydrogen, and Rg is methyl. Particularly preferred compounds of the formula I are 4 ', 7-diacetoxyisoflavone (daidzein diacetate) and 7-acetoxy-4' -methoxyisoflavone; Particularly preferred compounds of formula II are ', 7-diacetoxyisoflavan-4-ol (tetrahydrodaidzein diacetate) and 7-acetoxy-4' -me oxyisoflavan-4-ol; particularly preferred compounds of formula III are 4 ', 7-diacetoxyisoflav-3-ene (dehydroequol diacetate), 4', 7-dihydroxyisoflav-3-ene (dehydroequol), 7-acetoxy-4-methoxyisoflav-3-r eno and 7-hydroxy-4 '-methoxyisoflav-3-ene; Particularly preferred compounds of formula IV are 4 ', 7-diacetoxyisoflavan-4-one (diacetoxydihydrodaidzein) and 4', 7-dihydroxyisoflavan-4-one (dihydrodaidzein); and particularly preferred compounds of formula V are 4 ', 7-diacetoxyisoflavan (diacetate equol) and', 7-dihydroxyisoflavan (equol). The novel compounds of the formulas I, II, III, IV and V preferably have the following substituents wherein Ri is hydroxy, OR9, OC (0) Rg, thio, alkylthio or halo, R2, R3, R, R5, Rs , R7 and R8 are independently hydrogen, hydroxy, ORg, 0C (0) R9, OS (0) R9, alkyl, aryl, thio, alkylthio or halo, and Rg is alkyl, fluoroalkyl or arylalkyl with the proviso that at least one R5, Re and R is not hydrogen, or when R5, R6 and R7 are all hydrogen, then R3 is hydroxy, 0R9, OC (0) R9, 0S (0) R9, alkyl, aryl , thio, alkylthio or halo; and most preferably have the following substituents wherein Ri is hydroxy, ORg or 0C (0) R9, R2 and R3 are independently hydrogen, hydroxy, 0R9 or OC (0) R9, R, R5, R6 and Rs are hydrogen, R7 is hydroxy, ORg, 0C (0) R9, alkyl, aryl or halo, and Rg is methyl, ethyl, propyl, isopropyl, trifluoromethyl or benzyl; or wherein Ri is hydroxy, ORg, 0C (0) R9, R2 and 3 are independently hydrogen, hydroxy, ORg or OC (O) R9, R5 is 0R9, 0C (0) R9, alkyl, aryl or halo, R, Re, R7 and R8 are hydrogen, and R9 is methyl, ethyl, propyl, isopropyl, trifluoromethyl or benzyl. More preferably, the novel compounds of formulas I, II and III are: 4 ', 7, 8-Triacetoxyisoflavone 7,8-Diacetoxy-4' -methoxyisoflavone 4 ', 7-Diacetoxy-8-methylisoflavone 3', 7-Diacetoxy -8-methylisoflavone 7-Acetoxy-4 '-methoxy-8-methylisoflavone ', 7-Diacetoxy-3' -methoxy-8-methylisoflavone 4 ', 5,7-Triacetoxyisoflavone ', 7, 8-Triacetoxyisofla an-4-ol 7, 8-Diacetoxy-4-methoxyisoflavan- -ol 4', 7-Diacetoxy-8-methylisoflavan-4-ol 3 ', 7-Diacetoxy-8-methylisoflavan-4 -o1 7-Acetoxy-4 '-methoxy-8-methylisoflavan-4-ol 4', 7-Diacetoxy-3 '-methoxy-8-methylisoflavan-4-ol 4 ', 5, 7-Triacetoxiisoflavan-4-ol 4 ', 7, 8-Trihydroxyisoflavan-4-ol 7, 8 -Dihydroxy-4-methoxyisoflavan-4 -ol 4', 7-Dihydroxy-8-methylisoflavan-4-or 3 ', 7-Dihydroxy-8-methylisoflavan- 4-OH 7-Hydroxy-4 '-methoxy-8-methylisoflavan-4-ol 4', 7-Dihydroxy-3 '-methoxy-8-methylisoflavan-4-ol 4 ', 5,7-Trihydroxyisoflavan-4-ol 4 ', 7, 8-Triacetoxideshidroequol (4', 7,8-Triacetoxiisoflav-3-ene) 7,8-Diacetoxy-4-methoxideshydroequol (7,8-Diacetoxy-4-methoxyisoflav-3-ene) 4 ', 7 -Diacetoxy-8-methylisoflav-3-ene 3 ', 7-Diacetoxy-8-methylisoflav-3-ene 7-Acetoxy-4' -methoxy-8-methylisoflav-3-ene 4 ', 7-Diacetoxy-3' - methoxy-8-methylisoflav-3-ene ', 5, 7-Triacetoxiisoflav-3-ene Isoflav-3-ene-4 ', 7, 8 -triol 4' -Methoxyisoflav-3-ene-7,8-diol 8-Methylisoflav-3-ene-4 ', 7-diol 8 -Meti lisoflav-3-ene -3 ', 7 -diol' -Metoxy-8-methylisoflav-3-ene-7-ol 3 '-Metoxy-8-methylisoflav-3-ene-4', 7-diol Isoflav-3-ene-4 ', 5, 7-triol 4 ', 7 -Dihydroxy- 8 -methyl isoflavan- 4 -ol 7-Hydroxy-4' -methoxy-8-methylisofiavan-4-ol The term "alkyl" is taken to mean both straight chain and branched chain alkyl groups such as methyl, ethyl, propyl, isopropyl, butyl, isobutyl, secbutyl, tertiary butyl and the like. Preferably the alkyl group is lower alkyl of 1 to 6 carbon atoms. The alkyl group can be optionally substituted by one or more of fluorine, chlorine, bromine, iodine, carboxyl, C 1 -C 4 alkoxycarbonyl, C 1 -C 4 alkylaminocarbonyl, di- (C 1 -C 6 alkyl) amino. -carbonyl, hydroxyl, C? -C4 alkoxy, formyloxy, C? -C alkylcarbonyloxy, C? -C alkylthio, C3-Cd cycloalkyl or phenyl. The term "aryl" is taken to include phenyl and naphthyl and may optionally be substituted by one or more C? -C alkyl, hydroxy, C? ~ C4 alkoxy, carbonyl, C? ~ C4 alkoxycarbonyl, C? ~ C alkylcarbonyloxy or halo. The term "halo" is taken to have the meaning of one or more halogen radicals selected from fluorine, chlorine, bromine, iodine and mixtures thereof, preferably fluorine and chlorine, more preferably fluorine. Reference to, for example, "haloalkyl" includes monohalogenated, dihalogenated and even perhalogenated alkyl groups. Preferred perhalogenated groups are trifluoromethyl and pentafluoroethyl. The compounds of the invention include all salts, such as acid addition salts, anionic salts and zwitterionic salts and in particular include pharmaceutically acceptable salts. In all of this specification and in the claims that follow, unless the context requires otherwise, the word "comprise" and variations such as "comprises" or "comprising" shall be construed to imply the inclusion of a number. established whole or stage or group of integers or stages although without the excuse of any other integer or steps or group of integers or steps. Hydrogenation is ideally carried out with hydrogen in the presence of a reduction catalyst and a solvent. The reaction of preference is conducted under hydrogen at a pressure of 1-20 atmospheres, more preferably 1-5 atmospheres. The reaction can be carried out at 10 ° C to 60 ° C and is carried out typically at room temperature. The reaction time may vary from 12 hours to 96 hours or more and is typically about 55 hours or more. In general, the best performances and the cleanest reactions are achieved with longer reaction times. It will be appreciated that the reaction conditions may vary depending on the individual nature of the compounds and the progress of the hydrogenation reaction. The reduction catalysts can be selected from heterogeneous catalysts (whereby the catalyst is insoluble in the reaction medium) or homogeneous catalysts (whereby the catalyst is soluble in the reaction medium). Examples of heterogeneous reduction catalysts include Raney nickel, palladium black, palladium hydroxide or carbon, palladium or activated carbon (1% Pd at 30% Pd), palladium or alumina powder, palladium or various barium salts, nickel reduced with sodium borohydride, platinum metal, platinum black, platinum on activated carbon (1% Pt at 10% Pt), platinum oxide, rhodium salts, ruthenium salts and their chiral salts and zinc oxide. From Preferably, the catalyst is palladium or activated carbon (1% Pd at 10% Pd), more preferably 5% palladium on carbon. The platinum oxide (Adam catalyst) is also a hydrogenation catalyst very useful for the methods of the present invention to predominantly produce cis-isomers of isoflavan-4-ols. Examples of catalysts for homogeneous reduction include chlorotris (triphenylphosphine) rhodium, chlorine (trisphenylphosphine) hydruroruthenium (II) and pentacyanocobaltate (II). Suitable solvents for use in the present invention include, but are not limited to: Ci-Cs alcohols and polyols, alkyl acetates, tetrahydrofuran, ethers, dioxane and C 1 -C 3 acids. Preferably the solvent is a C? -C6 alcohol or a C? -C6 alkyl acetate, more preferably methanol, ethanol or ethyl lactate, as well as propanol, isopropanol, butanol, isobutanol, secbutanol, tertiary butanol, formate of methyl, ethyl formate and methyl acetate. Most preferably the solvent is absolute methanol, ethanol or ethyl acetate. The inventors of the present have found that with a sensible choice of catalysts, solvents and optionally protective groups, the isoflavones are reduced cleanly and in high yields to corresponding isoflavones. In Particularly, the use of methanol or absolute ethanol as a solvent provided for a very clean catalytic hydrogenation over 5% palladium in isoflavone charcoal to provide quantitative yields of isoflavanols. In the methods where, for example, 10% palladium on charcoal is used, the reaction can proceed more quickly in times that are completed in 12 hours. The ratio of cis- and trans-isomers of the hydrogenation product of isoflavan-4-ol may vary with the choice of catalysts and the nature of the isoflavone substitute. By varying the methods of the present invention, it is possible to influence the isomeric ratio reached during the reduction process. Of particular interest are isoflavones with oxygen substitution (or precursors for oxygen substitution) at the 4 'and 7 positions as the reduction of these compounds leads to the biologically important dehydroequol or precursors thereof. A convenient starting material is daidzein, which is easily obtained by established routes. It should be understood that some entities on the isoflavone rings may require protection or derivation before undergoing hydrogenation. For example, it might be desirable to protect free hydroxy entities with groups such as for example an acetoxy group to aid in the solubility of the substituted isoflavones and / or their susceptibility to hydrogenation. The protecting groups can be carried out by well-established methods known in the art., for example, as described in Pro tec ti ve Groups in Organi c Syn thesi s, T.. Greene. In particular, the inventors of the present have found it useful to protect the hydroxy groups when they occur as esters or ethers before reduction, with more favored acetoxy or methoxy groups. Preferably, the acylation is carried out with the hydroxy compounds in a solvent mixture of a carboxylic acid anhydride and a base. The protection of the free hydroxy groups before hydrogenation increases the yields up to quantitative yields. The reaction products are generally cleaner and do not require a chromatography step in the purification and isolation of the hydrogenation products. Thus, surprisingly, the tetrahydrodaidzein diacetate was obtained in quantitative yield when the catalytic hydrogenation of the diacetoxidaidzein in ethanol was continued for 55 hours. The spectroscopic analysis established that the product will be a 1: 1 mixture of ci s- and trans-isomers. It was noted with pleasure that there is no additional reduction of tetrahydrodaidzein even if the reduction continued for longer periods of time. In a similar manner, it was also surprisingly found that the protected isoflavone 7-acetoxy-4'-methoxydaidzein was gently and neatly subjected to hydrogenation in ethanol to produce a quantitative yield of a 1: 1 mixture of cis-and trans- isomers of 7-acetoxy-4 '-methoxyisoflavan-4-ol. This reaction appears to be very general and was repeated on many different substrates in amounts up to half a gram and more. With respect to this, the inventors have found conditions that allow the large-scale regeneration of clean and quasi-quantitative yields of the isoflavan-4-ols compounds by hydrogenation of the corresponding isoflavones. In particular, it has been found that amounts per kilogram of diacetoxy daidzein that undergo a smooth and efficient reduction for the cis- and trans- 4 ', 7-diacetoxyisoflavan-4-isols. The isomeric proportions can be influenced by the percentage of palladium in the catalyst. The cis- / traps-isomeric mixtures are capable of being dehydrated to isoflav-3-enos without the need for separation. However, it is desired that the mixtures be capable of separation by a variety of methods as set forth below.

The mixture of cis- and trans-tetrahydrodaidzein compounds are capable of separation by preparative HPLC. This mode of separation is very tedious and limited to small amounts of material. Because reasonable amounts of diacetoxy isoflavanols could be prepared, fractional crystallization was attempted to separate the cis- and trans-isomers. A simple recrystallization of the 1: 1 mixture of ethanol provided predominantly traps-diacetoxytetrahydrodaidzein (50% yield: purity 73%) (cis-isomer 27%). Subsequent recrystallization of the ethanol gave the pure trans-isomer in a total yield of 25%. Also, 7-acetoxy-1-methoxyisoflavan-4-ol was able to fractionally recrystallize to provide the pure trans-isomer, with the filtrate containing increased proportions of the cis-isomer. Most hydrogenations provided 1: 1 mixtures of ci s- and trans-isoflavan-4-ols. However, one observation derivative was 7-hydroxy-4'-methoxy-8-methylisoflavone, the hydrogenation of which provided predominantly the trans-isomer in excellent yield. The synthesis of tetrahydrodaidzein and related derivatives was achieved by eliminating the protective acetoxy groups under mild conditions, preferably with imidazole in refluxing ethanol. The tetrahydrodaidzein was isolated in an 80% yield after crystallization from aqueous ethanol. Dehydration of isoflavan-4-ols leads to unsaturated isoflav-3-ennes. Therefore, the reaction of a cis- / trans-mixture of isoflavan-4-ols with benzoyl chloride / dimethylformamide at 100 ° C has been reported in literature by Liepa to provide the desired isoflav-3-ene dehydration product . However, this reaction could only be repeated in low performance. The dehydration can also be carried out by treatment with acids such as, for example, sulfuric acid, hydrochloric acid, polyphosphoric acid, thionyl chloride and the like. Alternative methods for dehydration using p-toluenesulfonic acid or trifluoroacetic acid in refluxing dichloromethane were also investigated, although these methods also provided isoflavenos in low yields. In general, the inventors herein found that the dehydration reagent of choice to be phosphorus pentoxide in dichloromethane, which yielded isoplavians in yield greater than 60%. The dehydration reactions can be carried out in the hydrogenation products directly, or in the unprotected derivatives thereof. The synthesis of the dehydroequol was achieved by removing the protective acetoxy groups under mild conditions as described for the synthesis of tetrahydrodaidzein and the dehydroequol was purified by solvent mixtures for standard crystallization such as for example ethanol / water. Other isoflav-3-ene derivatives can be prepared by similar methods. The reduction by hydrogen of the 4 ', 7-diacetoxidaidzein with Adam catalyst (platinum (IV) oxide) in ethyl acetate under a hydrogen atmosphere provided 4 ', 7-diacetoxytetrahydrodaidzein. However, other than the reduction of palladium on charcoal in ethanol, reductions with Adam catalyst predominantly provided the cis-isomer of 4 ', 7-diacetoxytetrahydrodaidzein. In another embodiment of the invention, hydrogenation of 4 ', 7-diacetoxy daidzein with 5% palladium on charcoal in ethyl acetate as a solvent under a hydrogen atmosphere provided 4', 7-diacetoxydihydrodaidzein in excellent yield (80% ). These conditions provided access to isoflavan-4-ions from the corresponding isoflavones in good to excellent yields.

Access to isoplavane derivatives such as equol is possible by hydrogenation of isoflav-3-ennes with, preferably, palladium on charcoal in an alkyl acetate solvent under a hydrogen atmosphere. "Excellent yields of 75% and more of the hydrogenated products are obtained by these methods.The products are clean and recrystallized easily.The surprising results obtained by the inventors herein are in sharp contrast to those reported in the literature for other hydrogenations. of isoflavones tried A notable advantage is the use of alkyl acetates or alcohol solvents such as for example methanol or absolute ethanol in the hydrogenation reactions.The isoflavones prepared by the methods of the present invention are typically very crystalline and can be isolated in a good purity, and without the need for chromatography.Isoflavanols can be converted to isoflav-3-enos by dehydration.The additional deprotection or derivation steps can be employed by those skilled in the art to obtain natural isoflavan-4-ones , isoflavans, isoflavenos, metabolites and novel derivatives s of them as required. The invention is further described and illustrated by the following Examples. The Examples are not intended to be limiting of the invention in any way.

EXAMPLES Acetylation reactions Example 1 4 ', 7 Diacetoxidaidzein Method A A mixture of daidzein (1.Og, 3.9 mmol), acetic anhydride (5 ml) and pyridine (5 ml) was left in the dark at room temperature for 24 hours. The reaction mixture was poured into water (100 ml), stirred for 2 hours and then extracted with dichloromethane (3 x 50 ml). The dichloromethane layer was washed with water, dried over anhydrous sodium sulfate and evaporated. The white residue was crystallized from methanol to produce daidzein diacetate as white prisms (1.1 g, 83%). XH NMR (CDC13): d 2.32 (s, 3H, OCOCH3), 2.36 (s, 3H, OCOCH3), 7.18 (d, 2H, J 9.2 Hz, ArH), 7.19 (d, 1H, J 9.0 Hz, H6) , 7.31 (d, ÍH, J 2.0 Hz H8), 7.59 (d, 2H, J 9.2 Hz, ArH), 8.00 (s, ÍH, H2), 8.33 (d, 2H, J 8.2 Hz, ArH).

Method B A mixture of daidzein (2.0 g, 7.9 mmol), acetic anhydride (10 ml) and pyridine (2 ml) was heated in an oil bath at 105 ° C-110 ° C for 1 hour. hour. After cooling the mixture to room temperature, it was stirred for an additional 30 minutes during which time, the diacetate was crystallized from the solution. The product was filtered, washed thoroughly with water and recrystallized from methanol to give daidzein diacetate as colorless prisms (2.4 g, 90%).

EXAMPLE 2 7-Acetoxy-4'-methoxyisoflavone A mixture of 7-hydroxy-4'-methoxyisoflavanone (2.0 g, 7.5 mmol), acetic anhydride (10 ml) and pyridine (2 ml) was heated in an oil bath to 105 g. ° C-110 ° C for 1 hour. After cooling the mixture to room temperature, it was poured into water (100 ml), stirred for 2 hours and then extracted with dichloromethane (3 x 50 ml). The dichloromethane layer was washed with water, dried over anhydrous sodium sulfate and evaporated. The white residue was crystallized from methanol to provide 7-acetoxy-4'-methoxyisoflavone as colorless prisms (2.1g, 91%). XH NMR (CDC13): d 2.36 (s, 3 H, OCOCH 3), 3.84 (s, 3 H, OCH 3), 6.98 (d, 2 H, J 8.7 Hz, Ar H), 7.16 (dd, 1 H, J 1.9 Hz 8.6 Hz, H6), 7.30 (d, ÍH, J 1.9 Hz H8), 7.50 (d, 2H, J 8.7 Hz, ArH), 8.00 (s, ÍH, H2), 8.32 (d, 1H, J 8.6 Hz, H5).

Example 3 3 ', 7-Diacetoxyisoflavone 3', 7-Diacetoxidadzein was prepared from 3 ', 7-dihydroxyisoflavone (0.98 g, 3.9 mmol), acetic anhydride (6 ml) and pyridine (1.1 ml) as described for 4 ', 7-diacetoxidadzein. Yield: (l.Og, 77%) m.p. 152 ° C. XH NMR (CDC13): d 2.31 and 2.36 (each s, 3H, OCOCH3), 7.14 (m, ÍH, ArH), 7.18 (dd, ÍH, J 2.0 Hz 8.6 Hz, H6), 7.31 (d, ÍH, J 2.0 Hz H8), 7.37-7.45 (m, 3H, ArH), 8.03 (s, ÍH, H2), 8.32 (d, ÍH, J 8.6 Hz, H5). Mass spectrum: m / z 338 (M, 8%); 296 (53); 254 (100); 253 (60).

Example 4 7-Acetoxy-3 '-methoxyisoflavone 7-Acetoxy-3'-methoxyisoflavone was prepared from 7-hydroxy-3'-methoxyisoflavone (1.7 g, 6.3 mmol), acetic anhydride (6 ml) and pyridine (1.0 ml) ) as described for 4 ', 7-diacetoxidadzein. Yield: (1.6g, 81%) p.f. 118 ° C. 1ti NMR (CDC13): d 2.36 (s, 3H, OCOCH3), 3.85 (s, 3H, OMe), 6.95 (dd, ÍH, J 2.0 Hz 8.3 Hz, H6), 6.70-7.40 (m, 5H, ArH) , 8.01 (s, ÍH, H2), 8.32 (d, ÍH, J 8.7 Hz, H5).

Example 5 4 ', 7-Diacetoxy-3' -methoxyisoflavone 4 ', 7-Diacetoxy-3' methoxyisoflavone was prepared from '4', 7-dihydroxy-3 ' methoxyisoflavone (0.37 g, 1.3 mmol), acetic anhydride (2.5 ml) and pyridine (0.4 ml) as described for 4 ', 7-diacetoxidaidzein. Performance: (0.36g, 75%) p.f. 197 ° C. XH NMR (CDC13): d 2.33, 2.36 (each s, 3H, OCOCH3), 3.88 (s, 3H, OMe), 7.06-7.17 (m, 2H, ArH), 7.19 (dd, ÍH, J 2.3 Hz 9.0 Hz, ArH), 7.32 (dd, 2H, J 2.3 Hz 7.6 Hz, ArH), 8.03 (s, ÍH, H2), 8.32 (d, ÍH, J 8.6 Hz, H5).

EXAMPLE 6 7-Acetoxyisoflavone 7-Acetoxyisoflavone was prepared from 7-hydroxyisoflavone (2.6 g, 10.9 mmol), acetic anhydride (16 ml) and pyridine (3.0 ml) as described for 7'-diacetoxidadzein. Yield: (2.5g, 82%) p.f. 133 ° C. XH NMR (CDC13): d 2.36 (s, 3H, OCOCH3), 7.18 (dd, ÍH, J 2.2 Hz 8.6 Hz, H6), 7.31 (d, ÍH, J 2.2 Hz H8), 7.39-7.57 (m, 5H , ArH), 8.00 (s, ÍH, H2), 8.33 (d, ÍH, J 8.6 Hz, H5). Mass spectrum: m / z 280 (M, 28%); 237 (98); 238 (57).

Example 7 4 ', 7, 8-Triacetoxyisoflavone A mixture of 4', 7, 8-trihydroxyisoflavone (1.4 g, 5.2 mmol), acetic anhydride (8.4 ml) and pyridine (2 ml) was heated in an oil bath to a 105 ° C-110 ° C for 1 hour. After cooling the mixture to room temperature, it was stirred for additional minutes during which time the diacetate was crystallized from the solution. The product was filtered, washed thoroughly with water and recrystallized from ethyl acetate to provide 4 ', 7, 8-triacetoxyisoflavone as colorless prisms (1.49g, 73%) m.p. 190 ° C-192 ° C. XH NMR (CDC13): d 2.32, 2.36, 2.42 (each s, 3H, OCOCH3), 7.18 (d, 2H, J 8.6 Hz, ArH), 7.28 (d, ÍH, J 8.9 Hz, H6), 7.56 (d , 2H, J 8.6 Hz H8), 7.98 (s, ÍH, ArH), 8.18 (d, ÍH, J 8.9 Hz, H5).

EXAMPLE 8 7,8-Diacetoxy-4'-methoxyisoflavone 7,8-Diacetoxy-4'-methoxyisoflavone was prepared from 7,8-dihydroxy-4'-methoxyisoflavone (0.82g, 2.9 mmol), acetic anhydride (4.9 ml) and pyridine (0.9 ml) as described for 4 ', 7, 8-triacetoxyisoflavone. Yield: (0.9g, 85%) p.f. 165 ° C. XH NMR (CDC13): d 2.36, 2.42 (each s, 3H, OCOCH3), 3.84 (s, 3H, OCH3), 6.98 (d, 2H, J 9.0 Hz, ArH), 7.25 (d, ÍH, J 8.7 Hz , H6), 7.48 (d, 2H, J 9.0 Hz H8), 7.95 (s, 1H, H2), 8.20 (d, ÍH, J 9.1 Hz, H5). Mass spectrum: m / z 368 (M, 20%); 326 (15); 312 (18); 284 (80).

Example 9 4 ', 7-Diacetoxy-8-methylisoflavone A mixture of 4', 7-dihydroxy- Methylisoflavone (2.9 g, 10.8 mmol), acetic anhydride (18 ml) and pyridine (3 ml) was heated in an oil bath at 105 ° C-110 ° C for 1 hour. After cooling the mixture to room temperature, it was stirred for about 30 minutes during which time the diacetate was crystallized from the solution. The product was filtered, washed thoroughly with water and recrystallized from ethyl acetate to provide 4 ', 7-diacetoxy-8-methylisoflavone as colorless prisms (3.2g, 84%). XH NMR (CDC13): d 2.31 (s, 3H, CH3), 2.32, 2.39 (each s, 3H, OCOCH3), 7.13 (d, ÍH, J 9.0 Hz, H6), 7.17 (d, 2H, J 8.7 Hz , ArH), 7.59 (d, 2H, J 8.7 Hz, ArH), 8.07 (s, ÍH, H2), 8.19 (d, ÍH, J 8.7 Hz, H5).

Example 10 3 ', 7-Diacetoxy-8-methylxsoflavone 3', 7-Diacetoxy-8-methylisoflavone was prepared from 3 ', 7-dihydroxy-8-methylisoflavone (1.3g, 4.8 mmol), acetic anhydride (8 ml ) and pyridine (1.5 ml) as described for 4 ', 7-diacetoxy-8-methylisoflavone. Yield: (1.2g, 70%) p.f. 112 ° C. XH NMR (CDC13): d 2.31 (s, 3H, CH3), 2.32, 2.39 (each s, 3H, OCOCH3), 7.13 (m, 2H, ArH), 7.37-7.45 (m, 3H, ArH), 8.1 (s, ÍH, H2), 8.18 (d, ÍH, J 8.7 Hz, H5) . Mass spectrum: m / z 352 (M, 6%); 310 (35); 268 (100); 267 (60).

Example 11 7-Acetoxy-4'-methoxy-8-methylisoflavone 7-Acetoxy-4'-methoxy-8-methylisoflavone was prepared from 7-hydroxy-4'-methoxy-8-methylisoflavanone (3.0g, 10.6 mmole) acetic anhydride (10 ml) and pyridine (2.0 ml) as described for 4 ', 7-diacetoxy-8-methylisoflavone. Yield: (2.0g, 58%) p.f. 190 ° C-192 ° C. XH NMR (CDC13): d 2.31 (s, 3H, CH3), 2.38 (s, 3H, OCOCH3), 3.84 (s, 3H, OMe), 6.98 (d, 2H, J 8.7 Hz, ArH), 7.12 (d , H, J 8.6 Hz, H6), 7.52 (d, 2H, J 8.7 Hz, ArH), 8.03 (s, 1H, H2), 8.18 (d, 1H, J 8.6 Hz, H5). Mass spectrum: 325 (M + 1, 13%); 324 (M, 58%); 282 (100); 281 (42).

Example 12 4 ', 7-Diacetoxy-3' -metoxx-8-methylisoflavone 4 ', 7-Diacetoxy-3'-methoxy-8-methylisoflavone was prepared from 4', 7-dihydroxy-3'-methoxy-8 -methylsoflavone (0.42g, 1.4 mmol), acetic anhydride (2.6 ml) and pyridine (0.5 ml) as described for 4 ', 7-diacetoxy-8-methylisislavone. Yield: (0.4g, 74%) p.f. 209 ° C. 1 H NMR (CDCl 3): d 2.22 (s, 3 H, CH 3), 2.32, 2.39 (each s, 3 H, OCOCH 3), 3.89 (s, 3 H, OMe), 7.07-7.11 (m, 2 H, Ar H), 7.13 ( d, HH, J 8.6 Hz, H6), 7.32 (d, HH, J 1.5 Hz, ArH), 8.09 (s, HH, H2), 8.18 (d, HH, J 8.7 Hz, HS).

Hydrogenation reactions: -Isof lavona Isoflavan- 4-ol Example 13 4 ', 7-Diacetoxytetrahydrodaidzein (4'7-Diacetoxyisoflavan-4-ol) Method A Palladium on charcoal (5%, 0.08 g) was added to a suspension of 4', 7-diacetoxidaidzein (0.5 g, 1.5 mmol. ) in absolute ethanol (400 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 55 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide 4 ', 7-diacetoxytetrahydrodaidzein. (0.51 g, 100%) in quantitative yield. A nuclear magnetic resonance spectrum revealed that the product will be a clean 1: 1 mixture of cis- and trans-, 7-diacetoxytetrahydrodaidzein. The ci s- and trans-isomers were able to separate by fractional recrystallization. A 1: 1 mixture of cis- and trans-4 ', 7-diacetoxytetrahydrodaidzein (0.17 g), prepared as above, was dissolved in excess absolute ethanol and concentrated on a rotary evaporator. At the first sign of crystallization, the additional concentration of ethanol was stopped and the flask was cooled in an ice bath. The resulting crystals are filtered and washed with a small amount of cold absolute ethanol. A nuclear magnetic resonance spectrum of the product (0.08 g) revealed that it will be a mixture of trans-4 ', 1-diacetoxytetrahydrodaidzein (73%) and cis-4', 7-diacetoxytetrahydrodaidzein (27%). Further recrystallization of the mixture from ethanol gave pure trans-4 ', 7-diacetoxytetrahydrodaidzein (0.04 g, 24%). The filtrate provided predominantly cis-isomer. Nuclear magnetic resonance spectroscopic analysis revealed that the substance will be a mixture of cis-4 ', 7-diacetoxytetrahydrodaidzein (73%) and trans-4', 1-diacetoxytetrahydrodaidzein (27%). For trans-4 ', 7-Diacetoxyisoflavan-4-ol; • '' H NMR (CDC13): d 2.28 (s, 3H, 0C0CH3), 2.29 (s, 3H OCOCH3), 3.14 (ddd, 1H, J 3.7 Hz, 7.9 Hz, 9.1 Hz, H3), 4.24 (dd, ÍH, J 9.1 Hz, 11.3 Hz, H2); 4.35 (dd, ÍH, J 3.7 Hz, 11.3 Hz, H2), 4.87 (d, 1H, J 7.9 Hz, H4), 6.61 (d, ÍH, J 2.3 Hz, H8), 6.70 (dd, ÍH, J 2.3 Hz, 8.4 Hz, H6), 7.06 (d, 2H, J 8.6 Hz, ArH), 7.23 (d, 2H, J 8.4 Hz, ArH), 7.44 (dd, ÍH, J 0.8 Hz, 8.4 Hz, H5). 13C NMR (CDCl3): 20.98 (OCOCH3), 46.18 (C3), 68..04 (C2), 69.01 (C4), 109.67 (C8), 114.26 (C6), 121.96, 128.96 (ArCH), 129.40 (C5) . For cis-4 ', 7-Diacetoxyisoflavan-4-ol: 1 H NMR (CDCl 3): d 2.28 (s, 3 H, OCOCH 3), 2.29 (s, 3 H, OCOCH 3), 3. 30 (dt, ÍH, J 3.4 Hz, J 11.8 Hz, H3), 4.31 (ddd, 1H, J 1.4 Hz, 3.6 Hz, 10.5 Hz, H2); 4.56 (dd, ÍH, J 10.5 Hz, 11.8 Hz, H2), 4.75 (dd, ÍH, J 1.3 Hz, 3.2 Hz, H4), 6.66 (dd, 1H, J 2.3 Hz, 8.7 Hz, H6), 6.69 (d, ÍH, J 2.3 Hz, H8), 7.08 (d, 2H, J 8.6 Hz, ArH), 7.26 (d, ÍH, 8.4 Hz, H5), 7.29 (d, 2H, J 8.6 Hz ArH). 13C NMR (CDC13); 20.98 (OCOCH3), 43.52 (C3), 64.10 (C2), 66.46 (C4), 110.08 (C6), 114.09 (C8), 121.82, 129.40 (ArCH), 131.10 (C5).

Method B Palladium on charcoal (5%, 3.1 g) was added to a suspension of 4 ', 7-diacetoxidadzein (30.0 g) in absolute methanol (3600 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 55 hours The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide 4 ', 7-diacetoxytetrahydrodaidzein (29.5g, 96%). A nuclear magnetic resonance spectrum revealed that the product will be a clean 2: 1 mixture of cis- and trans- ', 7-diacetoxytetrahydrodaidzein.

Method C Palladium on charcoal (10%, 3. 0 g) to a suspension of 4 ', 7-diacetoxidadzein (30. lg) in absolute methanol (3600 ml) and the mixture was stirred at room temperature under an atmosphere of hydrogen for 15 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide 4 ', 7-diacetoxytetrahydrodaidzein (28.5g, 94%). A nuclear magnetic resonance spectrum revealed that the product will be a clean 1: 1 mixture of cis- and trans-4 ', 7-diacetoxytetrahydrodaidzein.

Method D Palladium on charcoal (5%, lOOg) was added to a suspension of 7-diacetoxidadzein. (980g) in absolute methanol (100L) and the mixture was stirred at room temperature under a hydrogen atmosphere for 78 hours. The catalyst was removed by filtration through a ceramic apparatus for candle filtration and the filtrate was evaporated in vacuo to provide 4 ', 7-diacetoxytetrahydrodaidzein (820g, 83%). A nuclear magnetic resonance spectrum revealed that the product will be a clean 2: 1 mixture of cis- and trans-4 ', 7-diacetoxytetrahydrodaidzein.

Example 14 Synthesis of 7-Acetoxy-4'-methoxyisoflavan-4-ol Palladium on charcoal (5%, 0. 08g) to a suspension of 7-acetoxy-4'-methoxyisoflavone (0.5g, 1.6 mmol) in absolute ethanol (400 ml) and the mixture was stirred at room temperature. environment under a hydrogen atmosphere for 55 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide 7-acetoxy-4'-methoxyisoflavan-4-ol (0.51g, 100%) in quantitative yield. A nuclear magnetic resonance spectrum revealed that the product will be a clean 1: 1 mixture of .ci s- and trans- 1 -acetoxy-4 '-methoxyisoflavan-4-ol. The ci s- and trans-isomers were able to separate by fractional recrystallization. A 1: 1 mixture of cis- and trans-4 ', 7-diacetoxytetrahydrodaidzein, was prepared as above, recrystallized three times from ethanol to provide pure trans-7-acetoxy-4'-methoxyisoflavan-4-ol. The filtrate provided predominantly cis-isomer. For trans-7-Acetoxy-4 '-methoxyisoflavan-4-ol; 1R NMR (CDC13): d 2.31 (s, 3H, OCOCH3), 3.14 (dt, ÍH, J 3.8 Hz, 8.6 Hz, H3), 3.82 (s, 3H, OCH3), 4.25 (dd, ÍH, J 9.4 Hz , 11.3 Hz, H2); 4.37 (dd, ÍH, J 4.1 Hz, 11.3 Hz, H2), 4.93 (d, 1H, J 7.8 Hz, H4), 6.63 (d, 1H, J 2.3 Hz, H8), 6.73 (dd, 1H, J 2.3 Hz, 8.3 Hz, H6), 6.93 (d, 2H, J 8.7 Hz, ArH), 7.19 (d, 2H, J 8.7 Hz, ArH), 7.51 (d, ÍH, J 7.9 Hz, H5). For cis-7-Acetoxy-4 '-methoxyisoflavan-4-ol; XH NMR (CDC13): d 2.30 (s, 3H, OCOCH3), 3.28 (dt, ÍH, J 3.4 Hz, J 12.1 Hz, H3), 3.84 (s, 3H, OCH3), 4.36 (ddd, ÍH, J 1.4 Hz, 3.8 Hz, 10.1 Hz, H2); 4.57 (dd, ÍH, J . 1 Hz, 11.3 Hz, H2), 4.75 (bs, ÍH, H4), 6.58 (d, ÍH, J 2.3 Hz, H8), 6.75 (dd, ÍH, J 2.3 Hz, 8.3 Hz, H6), 6.96 (d, 2H, 'j 8.6 Hz, ArH), 7.25 (d, 2H, 8.6 Hz, ArH), 7.34 (d, ÍH, J 8.3 Hz, H5).

EXAMPLE 15 3'-7-Diacetoxyisoflavan-4-ol Palladium on charcoal (5%, 0.03 g) was added to a suspension of 3 ', 7-diacetoxyisoflavanone (0.2 g, 0.6 mmol) in methanol (50 ml) and the The mixture was stirred at room temperature under a hydrogen atmosphere for 55 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide 3'-7-diacetoxyisoflavan-4-ol in quantitative yield. A nuclear magnetic resonance spectrum revealed that the product will be a clean 1: 1 mixture of cis- and trans-3'-7-diacetoxyisoflavan-4-ol. For trans-3 '-7-diacetoxy isoflavan--ol; LH NMR (CDC13): d 2.31 and 2.32 (each s, 3H, OCOCH3), 3.17 (ddd, ÍH, J 3.6 Hz, 8.6 Hz, 11.2 Hz, H3), 4.26 (dd, ÍH, J 9.2 Hz, 11.6 Hz, H2); 4.33 (m, HH, H2), 4.91 (d, HH, J 7.9 Hz, H4), 6.60-6.73 (m, ArH), 6.97-7.16 (m, ArH), 7.25-7.48 (m, ArH). For cis-3'-7-diacetoxyisoflavan-4-ol; 1 H NMR (CDCl 3): d 2.30 and 2.31 (each s, 3H, OCOCH 3), 3.31 (dt, ÍH, J 3.3 Hz, J 11.6 Hz, H3), 4.31 (m, ÍH, H2); 4.57 (dd, 1H, J 10.6 Hz, 11.9 Hz, H2), 4.79 (bs, ÍH, H4), 6. 60-6.73 (m, ArH), 6.97-7.16 (m, ArH), 7.25-7.48 (m, ArH).

Example 16 7-Acetoxy-3'-methoxyisoflavan-4-ol ci s- and trans-7-acetoxy-3 '-methoxyisoflavan-4-ol were prepared from 7-acetoxy-3' -methoxyisoflavone (0.5g, 1.6 mmoles) and palladium on charcoal (5%, 0.12 g) in methanol (100 ml) by the method described above. For trans-7-acetoxy-3 '-methoxyisoflavan-4-ol; 1R NMR (CDC13): d 2.28 (s, 3H, OCOCH3), 3.15 (ddd, ÍH, J 3.8 Hz, 8.3 Hz, 12.0 Hz, H3), 3.80 (s, 3H, OMe), 4.26 (dd, 1H, J 9.4 Hz, 11.3 Hz, H2); 4.32 (m, ÍH, H2), 4.95 (d, ÍH, J 7.9 Hz, H4), 6.60-6.93 (m, ArH), 7.23-7.33 (m, ArH), 7.49 (d, J 8.7 Hz, ArH) . For cis-7-acetoxy-3 '-methoxyisoflavan-4-o1; 1U NMR (CDC13): d 2.28 (s, 3H, OCOCH3), 3.30 (dt, ÍH, J 3.3 Hz, J 11.7 Hz, H3), 4.31 (m, ÍH, H2); 4.58 (dd, ÍH, J 10.5 Hz, 11.7 Hz, H2), 4.81 (bs, ÍH, H4), 6.60-6.93 (m, ArH), 7.23-7.33 (m, ArH), 7.49 (d, J 8.7 Hz , ArH).

EXAMPLE 17 4 ', 7-Diacetoxy-3' -methoxyisovan-4-ol cis- and trans-4'-7-diacetoxy-3'-methoxyisoflavan-4-ol were prepared from 4'-7-diacetoxy- 3'-methoxyisoflavone (0.25g, 0.7 mmole) and palladium on charcoal (5%, 0.06 g) in methanol (50 ml) by the method described above. For trans-, -1-diacetoxy-3 '-methoxyisoflavan-4-ol; XH NMR (CDC13): d 2.29, 2.31 (each s, 3H, OCOCH3), 3.17 (ddd, ÍH, J 3.8 Hz, 8.7 Hz, 12.5 Hz, H3), 3.79 (s, 3H, OMe), 4.26 (dd) , ÍH, J 9.4 Hz, 11.3 Hz, H2); 4.32 (m, ÍH, H2), 4.93 (d, ÍH, J 7.9 Hz, H4), 6.62-6.73 (m, ArH), 6.81-6.91 (m, ArH), 6.99-7.05 (m, ArH), 7.30 (d, J 8.3 Hz, ArH), 7.48 (d, J 9.0 Hz, ArH). For cis-7-acetoxy-3 '-methoxyisoflavan-4-ol; XH NMR (CDCl 3): d 2.31, 2.32 (each s, 3H, OCOCH 3), 3.33 (dt, ÍH, J 3.3 Hz, J 11.3 Hz, H3), 3.83 (s, 3H, OMe), 4.31 (m, ÍH , H2); 4.58 (t, ÍH, J 10.5 Hz, H2), 4.82 (bs, ÍH, H4), 6.62-6.73 (m, ArH), 6.81-6.91 (m, ArH), 6.99-7.05 (m, ArH), 7.30 (d, J 8.3 Hz, ArH), 7.48 (d, J 9.0 Hz, ArH).

Example 18 7-Acetoxyisoflavan-4-ol Cis- and trans-7-acetoxyisoflavan-4-ol was prepared from 7-acetoxyisoflavone (0.4g, 1.4 mmole) and palladium on charcoal (5%, 0.09g) in methanol absolute (60 ml). P.f. 90 ° C. Mass spectrum: m / z 284 (M, 10%); 226 (42); 138 (100); 137 (58). For rans-7 -acetoxyisoflavan- 4 -ol; -H NMR (CDCI3): d 2.29 (s, 3H, OCOCH3), 3.17 (m, ÍH, H3) 4. 27 (t, ÍH, J 10.6 Hz, H2); 4.30 (m, 1H, H2), 4.97 (d, ÍH, J 8.3 Hz, H4), 6.60-6.73 (m, ArH), 7.08 (d, J 8. 7 Hz, ArH), 7.23-7.37 (m, ArH), 7.49 (d, J 8.7 Hz, ArH). For cis-7-acetoxyisoflavan-4-ol; 1H NMR (CDC13): d 2.30 (s, 3H, OCOCH3), 3.33 (dt, ÍH, J 3.4 Hz, J 11.7 Hz, H3), 4.36 (m, ÍH, H2); 4.62 (t, ÍH, J 10.5 Hz, H2), 4.80 (bs, ÍH, H4), 6.60-6.73 (m, ArH), 7. 08 (d, J 8.7 Hz, ArH), 7.23-7.37 (m, ArH), 7.49 (d, J 8.7 Hz, ArH).

Example 19 4 ', 7, 8-Trxacetoxiisoflavan-4-ol Palladium on charcoal (5%, 0.07 g) was added to a suspension of 4', 7, 8-triacetoxyisoflavone (0.5 g, 1.3 mmol) in methanol (100 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 55 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide 4 ', 7, 8-triacetoxyisoflavan-4-ol in quantitative yield. A nuclear magnetic resonance spectrum revealed that the product will be a clean 1: 1 mixture of cis- and tran s- 4 ', 7, 8-triacetoxiisoflavan-4-ol. Mass spectrum: m / z 400 (M, 5%); 358 (12); 298 (12); 256 (24); 196 (20); 162 (70); 154 (100); 120 (80). For trans- 4 ', 7, 8-triacetoxyisoflavan-4-ol; XH NMR (CDCI3): d 2.28, 2.29, 2.31 (each s, 3H, OCOCH3), 3.20 (m, 1H, H3), 4.27 (dd, 1H, H2); 4.37 (m, ÍH, H2), 4.93 (d, 1H, J 7.9 Hz, H4), 6.78 (d, ÍH, J 8.3 Hz, H8), 7.09 (m, ArH), 7.11-7.31 (, ArH), 7.39 (d, ÍH, J 8.7 Hz, ArH). For cis-4 ', 7, 8-triacetoxyisoflavan-4-ol; 1H NMR (CDC13): d 2.30, 2.31, 2.32 (each s, 3H, OCOCH3), 3.35 (m, ÍH, H3), 4.38 (m, 1H, H2); 4.57 (t, ÍH, J 10.6 Hz, H2), 4.75 (bs, ÍH, H4), 6.78 (d, ÍH, J 8.3 Hz, H8), 7.09 (m, ArH), 7.11-7.31 (m, ArH) , 7.39 (d, ÍH, J 8.7 Hz, ArH).

Example 20 7,8-Diacetoxy-4-methoxyisovan-4-ol 7,8-Diacetoxy-4-methoxyisoflavan-4-ol was prepared from 7,8-dihydroxy-4'-methoxyisoflavone (0.4 g, 1.1 mmol) in methanol (120 ml) using palladium on charcoal (5%, 0.08 g) by the method described above. For trans-1, 8-diacetoxy-4-methoxyisoflavan-4-ol; XH NMR (CDCI3): d 2.29, 2.30 (each s, 3H, OCOCH3), 3.14 (ddd, ΔH, J 3.9 Hz, 9.2 Hz, 12.5 Hz, H3), 3.79 (s, 3H, OCH3), 4.24 (dd , ÍH, J 9.6 Hz, 11.2 Hz, H2); 4.35 (m, ÍH, H2), 4.92 (d, ÍH, J 7.8 Hz, H4), 6.78 (d, 1H, J 8.6 Hz, H6), 6.90 (m, ArH), 7.13-7.22 (m, ArH) , 7.38 (d, J 8.6 Hz, ArH). For cis-1, 8-diacetoxy-4-methoxyisoflavan-4-ol; XH NMR (CDC13): d 2.30, 2.31 (each s, 3H, OCOCH3), 3.29 (dt, 1H, J 3.0 Hz, J 12.0 Hz, H3), 3.80 (s, 3H, OCH3), 4.36 (m, ÍH, H2); 4.57 (t, ÍH, J 10.6 Hz, H2), 4.75 (bs, 1H, H4), 6.77 (d, ÍH, J 8.6 Hz, H6), 6.90 (m, ArH), 7.13-7.22 (m, ArH) , 7.38 (d, J 8.6 Hz, ArH).

Example 21 4 ', 7-Diacetoxy-8-methylisoflavan-4-ol Palladium on charcoal (5%, 0.12 g) was added to a suspension of 4', 7-diacetoxy-8-methylisislavone (l.Og, 2.8 mmol ) in methanol (200 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 55 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to yield 7, 7-diacetoxy-8-methylisoflavan-4-ol in quantitative yield, m.p. 135 ° C-37 ° C. A nuclear magnetic resonance spectrum revealed that the product will be a clean 1: 1 mixture of cis- and trans-4 ', 7-diacetoxy-8-methylisoflavan-4-ol. Mass spectrum: 356 (M, 53%); 254 (86); 253 (100); 240 (80); 196 (37). For trans- 4 ', 7-diacetoxy-8-methylisoflavan-4-ol; aH NMR (CDC13): d 2.02 (s, 3H, CH3), 2.30, 2.31 (each s, 3H, OCOCH3), 3.15 (ddd, ÍH, J 3.8 Hz, 8.6 Hz, 11.7, H3), 4.27 (dd, 1H, J 9.4 Hz, 11.3 Hz, H2); 4.39 (m, 1H, H2), 4.92 (d, ÍH, J 7.5 Hz, H4), 6.64 (d, H, J 8.0 Hz, H6), 7.06-7.32 (m, ArH). For cis-4 ', 7-diacetoxy-8-methylisoflavan-4-ol; XH NMR (CDC13): d 2.02 (s, 3H, CH3), 2.31, 2.32 (each s, 3H, OCOCH3), 3.28 (dt, ÍH, J 3.4 Hz, J 11.7 Hz, H3), 4.40 (m, ÍH, H2); 4.58 (dd, ÍH, J 10.1 Hz, 11. 7 Hz, H2), 4.78 (bs, ÍH, H4), 6.67 (d, ÍH, J 8.0 Hz, H6), 7.06-7.32 (m, ArH).

Example 22 3 ', 7-Diacetoxy-8-methylisoflavan-4-ol 3', 7-Diacetoxy-8-methylisoflavan-4-ol was prepared from 3 ', 7-diacetoxy-8-methylisislavone (0.25 g, 0.7 mmol) in methanol (50 ml) using palladium on charcoal (5%, 0.06 g) by the method described above. For trans- 3 ', 7-diacetoxy-8-met ilisoflavan-4-ol; 1R NMR (CDCI3): d 2.03 (s, 3H, CH3), 2.30, 2.32 (each s, 3H, OCOCH3), 3.18 (ddd, ÍH, J 3.8 Hz, 8.3 Hz, 12.1 Hz, H3), 4.28 (dd, ÍH, J 9.0 Hz, 10.9 Hz, H2); 4.39 (m, 1H, H2), 4.94 (d, ÍH, J 8.7 Hz, H4), 6.65 (d, ÍH, J 7.9 Hz, H6), 6.98-7.39 (m, ArH). For cis-3 ', 7-diacetoxy-8-methylisoflavan-4-ol; XH NMR (CDC13): d 2.05 (s, 3H, CH3), 2.30, 2.32 (each s, 3H, OCOCH3), 3.32 (dt, ÍH, J 3.4 Hz, J 12.0 Hz, H3), 4.39 (m, ÍH, H2); 4.59 (dd, 1H, J 10.5 Hz, 11.7 Hz, H2), 4.80 (bs, 1H, H4), 6.68 (d, 1H, J 8.3 Hz, H6), 6.98-7.39 (m, ArH).

Example 23 7-Acetoxy-4'-methoxy-8-metxlxsoflavan-4-ol 7-Acetoxy-4'-methoxy-8- was prepared metilisoflavan-4-ol from 7-hydroxy-4 '-methoxy-8-methylisoflavone (0.25 g, 0.8 mmol) in methanol (50 ml) using palladium on charcoal (5%, 0.08 g) by the method described above . This hydrogenation reaction predominantly provided the trans-isomer. For trans-1-Acetoxy-1-methoxy-8-methylisoflavan-4-ol; H NMR (CDC13): d 2.02 (s, 3H, CH3), 2.32 (s, 3H, OCOCH3), 3.11 (ddd, ÍH, J 3.8 Hz, 9.4 Hz, 12.1 Hz, H3), 3.80 (s, 3H, OMe), 4.25 (dd, ÍH, J 9.4 Hz, 11.3 Hz, H2); 4.40 (dd, HH, J 3.8 Hz, 12.6 Hz, H2), 4.92 (bd, 1H, H4), 6.67 (d, HH, J 8.3 Hz, H6), 6.89 (d, 2H, J 8.7 Hz, ArH) , 7.16 (d, 2H, J 8.7 Hz, ArH), 7.34 (d, ÍH, J 8.3 Hz, H5).

Example 24 4 ', 7-Diacetoxy-3'-methoxy-8-methylisoflavan-4-ol 4', 7-Diacetoxy-3'-methoxy-8-methylisoflavan-4-ol was prepared from 4 ', 7- diacetoxy-3'-methoxy-8-methylisoflavone (0.25 g, 0.7 mmol) in methanol (50 ml) using palladium on charcoal (5%, 0.07 g) by the method described above. For trans- 4 ', 7-diacetoxy-3' -methoxy-8-methylisoflavan-4-ol; XH NMR (CDC13): d 2.05 (s, 3H, CH3), 2.30, 2.32 (each s, 3H, OCOCH3), 3.18 (ddd, ÍH, J 3.8 Hz, 8.3 Hz, 11.4 Hz, H3), 3.79 (s , 3H, OMe), 4.28 (dd, ÍH, J 9.0 Hz, 11.3 Hz, H2); 4.41 (m, ÍH, H2), 4.93 (d, ÍH, J 7.9 Hz, H4), 6.64 (d, ÍH, J 7.9 Hz, H6), 6.75-6.92 (m, ArH), 7.00 (d, ÍH, J 7.9 Hz, ArH) , 7.16 (d, ÍH, J 8.3 Hz, ArH). For cis-3 ', 7-diacetoxy-8-methylisoflavan-4-ol; 1H NMR (CDC13): d 2.05 (s, 3H, CH3), 2.30, 2.32 (each s, 3H, 0C0CH3), 3.29 (dt, ÍH, J 3.4 Hz, J 11.7 Hz, H3), 4.40 (, 1H, H2); 4.59 (t, 1H, J 10.5 Hz, H2), 4.81 (bs, ÍH, H4), 6.67 (d, ÍH, J 7.9 Hz, H6), 6.75-6.92 (m, ArH), 7.03 (d, 1H, J 8.3 Hz, ArH), 7.33 (d, 1H, J 8.3 Hz, ArH).

Dehydration reactions Example 25 4 ', 7-Diacetoxideshydroequol (41,7-Dxacetoxxxsoflav-3-ene) Method A Distilled trifluoroacetic acid was added (0.1 ml) was added to a solution of cis- and trans-4 ', 7-diacetoxytetrahydrodaidzein (O.lg) in dry distilled dichloromethane (15 ml) and the mixture was brought to reflux under argon. The progress of the reaction was monitored by thin layer chromatography and additional portions of 0.1 ml of trifluoroacetic acid were added. After refluxing for 4 hours, the reaction mixture was cooled and washed successively with saturated solution with sodium bicarbonate, water and brine. The resulting organic phase was dried, concentrated, subjected to chromatography and crystallized to provide 4 ', 7-diacetoxyhydroquinol as colorless prisms (0.034g, 35%). 1H NMR (CDC13 + d6-DMSO): d 2.29 (s, 3H, OCOCH3), 2.31 (s, 3H, OCOCH3), 5.15 (s, 2H, H2), 6.62 (bs, 1H, H4), 6.65 (dd , ÍH, J 2.1 Hz 8.2 Hz, H6), 6.75 (bs, ÍH, H8), 7.06 (d, ÍH, J 8.2 Hz H5), 7.12 (d, 2H, J 8.2 Hz, ArH), 7.43 (d, 2H, J 8.2 Hz, ArH).

Method B p-Toluenesulfonic acid (0.02 g) was added to a solution of cis- and trans-4'1-diacetoxytetrahydrodaidzein (0.1 g) in dry distilled dichloromethane (15 ml) and the mixture was brought to reflux under argon. The progress of the reaction was monitored by thin layer chromatography and after 4 hours under reflux, the reaction mixture was passed through a short column of silica gel and the eluent was recrystallized from ethanol to provide 4 '. , 7-diacetoxideshidroequol as colorless prisms (0.025 g, 26%).

Method C Phosphorus pentoxide (5g) was added with stirring to a solution of cis- and trans-4 ', 7-diacetoxytetrahydrodaidzein (1.Og) in dry dichloromethane (80 ml). The mixture was stirred at room temperature for 2 hours and filtered through a Celite pad. The dichloromethane solution was concentrated and subjected to chromatography on silica gel to provide 4 ', 7-diacetoxyhydroquinol as colorless prisms (064g, 26%).

Example 26 7-Acetoxx-4 '-methoxyisoflav-3-ene Phosphorus pentoxide (l.Og) was added with stirring to a solution of cis- and trans-acetoxy-4'-methoxyisoflavan-4-ol (O.lg. , 0.3 mmol) in dry dichloromethane (20 ml). The mixture was stirred at room temperature for 2 hours and filtered through a pad of Celite. The organic phase was concentrated and chromatographed on silica gel to provide 7-acetoxy-4 '-methoxyisoflav-3-ene (0.04 g, 42%). XH NMR (CDC13); d 2.28 (s, 3H, OCOCH3), 3.83 (s, 3H, OCH3), 5.14 (s, 2H, H2), 6.61 (dd, ÍH, J 2.3 Hz 6.4 Hz, H6), 6.65 (d, ÍH, J 2.3 Hz, H8), 6.69 (bs, ÍH, H4), 6.92 (d, 2H, J 9.0 Hz ArH), 7.04 (d, ÍH, J 7.9 Hz, H5), 7.37 (d, 2H, J 9.0 Hz, ArH).

Example 27 3 ', 7-Diacetoxideshidroequol (3', 7-Diacetoxyisoflav-3-ene) 3 '-7-Diacetoxyisoflav-3-ene was prepared from cis- and trans-3', 7-diacetoxyisoflavan-4-ol (0.2 g, 0.6 mmol) in dry dichloromethane (50 ml) using phosphorus pentoxide (2.0g). Performance: (0.09g, 48%). XH NMR (CDC1): d 2.29 and 2.32 (each s, 3H, OCOCH3), 5.14 (s, 2H, H2), 6.61 (d, ÍH, J 2.3 Hz, H8), 6.66 (dd, 1H, J 2.3 Hz 7.9 Hz, H6), 6.79 (bs, ÍH, H4), 7.02-7.15 (m, 3H, ArH), 7.25-7.44 (m, 2H, ArH).

Example 28 7-Acetoxy-3 '-methoxydishydroequol (7-Acetoxy-3'-methoxyisoflav-3-ene) 7-Acetoxy-3'-methoxyisoflav-3-ene was prepared from cis- and trans-1 -acetoxy- 3'-methoxyisoflavan-4-ol (0.25 g, 0.8 mmol) in dry dichloromethane (20 ml) using phosphorus pentoxide (2.0 g). Performance: (0.15g, 63%). X H NMR (CDCl 3): d 2.28 (s, 3 H, OCOCH 3), 3.85 (s, 3 H, OMe), 5.15 (s, 2 H, H 2), 6.60-6.67 (m, 2 H, Ar H), 6.78 (bs, 1 H) , H4), 6.84-7.06 (m, 4H, ArH), 7.35 (t, ÍH, J 8.6 Hz, ArH).

Example 29 4 ', 7-Diacetoxy-3' -methoxyiso lav-3-ene 4 ', 7-Diacetoxy-3'-methoxyisoflav-3-ene was prepared from cis- and trans-', 7-diacetoxy-3 '-methoxysoflavan-4-ol (0.20g, 0.5 mmol) in dry dichloromethane (20 ml) using phosphorus pentoxide (2.0g). Yield: (O.llg, 58%).

EXAMPLE 30 7-Acehoxystrophy-3-ene 7-Acetoxyisoflav-3-ene was prepared from cis- and trans-7-acetoxyisoflavan-4-ol (0.4g, 1.4 mmol) in dry dichloromethane (60ml) using pentoxide phosphorus (5.0g). Performance: (0.2g, 53%) LH NMR (CDC13; d 2.29 (s, 3H, OCOCH3), 5.18 (s, 2H, H2), 6.61-6.67 (m, 2H, ArH), 6.79 (bs, ÍH, H4), 7.07 (d, ÍH, J 7.9 Hz, H5), 7.23-7.45 (m, 5H, ArH).

EXAMPLE 31 4 ', 7, 8-Triacetoxideshydroequol (4', 7,8-Triacetoxyisoflav-3-ene) Phosphorus pentoxide (5.0g) was added with stirring to a solution of cis- and trans-, 7, 8. -triacetoxiisoflavan-4-ol (0.5g, 1.3 mmol) in dry dichloromethane (50 ml). The mixture was stirred at room temperature for 2 hours and filtered through a pad of Celite. The resulting solution was concentrated and chromatographed on silica gel to provide 4,7,8-triacetoxyisoflav-3-ene (0.3g, 63%). XH NMR (CDC13): d 2.29, 2.31, 2.32, (each s, 3H, OCOCH3), 5.15 (s, 2H, H2), 6.72 (d, ÍH, J 8.3 Hz, H6), 6.75 (bs, ÍH, H4), 6.97 (d, ÍH, J 7.9 Hz, H5), 7.12 (d, 2H, J 8.7 Hz ArH), 7.41 (d, 2H, J 8.7 Hz, ArH).

EXAMPLE 32 7,8-Diacetoxy-4-methoxideshydroequol (7,8-Diacetoxy-4-methoxyiso lav-3-ene) 7,8-Diacetoxy-4-methoxyisoflav-3-ene was prepared from ci s- and trans -1,8-diacetoxy-4-methoxyisoflavan-4-ol (0.4g, 1.1 mmol) in dry dichloromethane (60 ml) using phosphorus pentoxide (5. Oq) Yield: (0.18g, 47%) LH NMR (CDC13): d 2.29, 2.32 (each s, 3H, OCOCH3), 3.83 (s, 3H, OCH3), 5.14 (s, 2H, H2), 6.69 (bs, 1H, H4), 6.71 (d, ÍH, J 8.3 Hz, H6), 6.90 (d, 2H, J 8.6 Hz ArH), 6. 95 (d, 1H, J 7.9 Hz, H5), 7.36 (d, 2H, J 8.6 Hz, ArH).

Example 33 4 ', 7-Dxacetoxy-8-methylxsoflav-3-ene Phosphorus pentoxide (3.0g) was added with stirring to a solution of cis- and trans-4', 7-diacetoxy-8-methylisoflavan-4- ol (0.55g, 1.5 mmol) in dry dichloromethane (25 ml). The mixture was stirred at room temperature for 2 hours and filtered through a pad of Celite. The resulting solution was concentrated and subjected to silica gel chromatography to provide ', 7-diacetoxy-8-methylisoflav-3-ene (0.25g, 48%). P.f. 140 ° C. NMR NMR (CDCI3): d 2.04 (s, 3H, CH3), 2.31, 2.32 (each s, 3H, OCOCH3), 5.16 (s, 2H, H2), 6.61 (d, ÍH, J 8.3 Hz, H6), 6. 75 (bs, 1H, H4), 6.94 (d, ÍH, J 8.3 Hz, H5), 7.13 (d, 2H, J 8.7 Hz, ArH), 7.45 (d, 2H, J 8.7 Hz, ArH). Mass spectrum: m / z 339 (M + 1, 6%); 338 (M, 26); 296 (48); 254 (90); 253 (100).

EXAMPLE 34 3 ', 7-Diacetoxy-8-methylisoflav-3-ene 3', 7-Diacetoxy-8-methylisoflav-3-ene was prepared from -de cis- and trans-3 ', 7-diacetoxy-8- metilisoflavan-4-ol (0.25 g, 0.7 mmol) in dry dichloromethane (20 ml) using phosphorus pentoxide (2.0 g). Yield: (0.13g, 54%) p.f. 116 ° C. 1H NMR (CDC13): d 2.04 (s, 3H, CH3), 2.31, 2.32 (each s, 3H, OCOCH3), 5.16 (s, 2H, H2), 6.61 (d, ÍH, J 8.3 Hz, H6), 6.79 (bs, ÍH, H4), 6.92 (d, ÍH, J 8.3 Hz, ArH), 7.05 (dd, 1H, J 2.0 Hz, 8.0 Hz, ArH), 7.15 (s, 1H, ArH), 7.26 (d , HH, J 8.0 Hz, ArH), 7.37 (t, HH, J 8.0 Hz, ArH). Mass spectrum: m / z 339 (M + 1, 15%); 338 (M, 22); 296 (54); 254 (30).

Example 35 7-Acetoxy-4'-methoxy-8-methylisoflav-3-ene 7-Acetoxy-4'-methoxy-8-methylisoflav-3-ene was prepared from cis- and trans-1 -acetoxy-4 ' -methoxy-8 -methyl isoflavan-4-ol (0.25 g, 0.7 mmol) in dry dichloromethane (20 ml) using phosphorus pentoxide (2.0 g). Yield: (O.llg, 46%) m.p. 107 ° C. X H NMR (CDCl 3): d 2.04 (s, 3 H, CH 3), 2.31 (s, 3 H, OCOCH 3), 3.83 (s, 3 H, OM e), 5.16 (s, 2 H, H2), 6.59 (d, ÍH, J 8.3 Hz, H6), 6.68 (bs, ÍH, H4), 6.90 (d, 1H, J 8.3 Hz, H5), 6.93 (d, 2H, J 9.0 Hz, ArH) , 7.37 (d, 2H, J 9.0 Hz, ArH). Mass spectrum: m / z 311 (M + 1, 13%); 310 (M, 68); 267 (100); 152 (68); 135 (90).

Example 36 4 ', 7-Diacetoxy-3' -metoxx-8-metxlisoflav-3-ene 4 ', 7-Diacetoxy-3'-methoxy-8-methylisoflav-3-ene was prepared from ci s- and trans -4 ', 7-diacetoxy-3' -methoxy-8-methylisoflavan-4-ol (0.25 g, 0.6 mmol) in dry dichloromethane (25 ml) using phosphorus pentoxide (2.0 g). Yield: (0.14g, 58%) p.f. 123 ° C. XH NMR (CDC13): d 2.05 (s, 3H, CH3), 2.31, 2.32 (each s, 3H, OCOCH3), 3.88 (s, 3H, OMe), 5.16 (s, 2H, H2), 6.61 (d, ÍH, J 8.3 Hz, H6), 6.73 (bs, ÍH, H4), 6.94 (d, ÍH, J 8.3 Hz, H5), 6.97 (dd, ÍH, J 1.9 Hz, 8.3 Hz, ArH), 7.03 (d , HH, J 1.9 Hz, ArH), 7.05 (d, HH, J 7.9 Hz, ArH).

Deprotection reactions Example 37 Dehydroequol (Isoflav-3-ene-4 ', 7-diol) Imidazole (0.09 g) was added to a suspension of 4', 7-diacetoxyhydroquinol (0.03 g, 0.09 mmol) in absolute ethanol (2.0 ml. ) and the mixture was refluxed for 45 minutes under argon. The solution was concentrated under reduced pressure and the product was precipitated by the addition of distilled water (10 ml). The mixture was left overnight in the refrigerator and filtered to provide dehydroequol. The crude product was reprecipitated from methanol by the addition of benzene to provide dehydroequol as a fluffy white solid (0.012 g, 55%). 1H NMR (CDC13 + d6_DMSO): d 4.93 (s, 2H, H2), 6.26 (bs, ÍH, H4), 6.29 (dd, ÍH, J 2.0 Hz, 8.2 Hz, H6), 6.50 (bs, ÍH, H8 ), 6.73 (d, 2H, J 8.2 Hz, ArH), 6.76 (d, 2H, J 8.2 Hz, H5), 7.13 (d, 2H, J 8.2 Hz, ArH).

Example 38 7-Hydroxy-4'-methoxyisoflav-3-ene Imidazole (0.18g) was added to a suspension of 7-acetoxy-4'-methoxyisoflav-3-ene (0.06g, 0. 02 mmoles) in absolute ethanol (5.0 ml) and the mixture was refluxed for 45 minutes under argon. The solution was concentrated under reduced pressure and the product was precipitated by the addition of distilled water (10 ml). The mixture was left overnight in the refrigerator and filtered to provide isoflav-3-ene. The crude product was recrystallized from methanol / benzene to provide 7-hydroxy-4'-methoxyisoflav-3-ene (0.034g, 66%). XH NMR (CDC13 + d6-DMSO): d 3.74 (s, 3H, OCH3), 4.99 (s, 2H, H2), 6.21 (d, ÍH, J 2.3 Hz, H8), 6.29 (dd, ÍH, J 2.3 Hz, 8.3 Hz, H6), 6.67 (bs, ÍH, H4), 6.85 (d, ÍH, J 8.3 Hz, H5), 6.86 (d, 2H, J 8.7 Hz, ArH), 7.33 (d, 2H, J 8.7 Hz, ArH).

Example 39 Isoflav-3-ene-3 ', 7-diol Isoflav-3-ene-3', 7-diol was prepared from 3 ', 7-diacetoxyisoflav-3-ene (0.09 g, 0.3 mmol) and imidazole (0.3g) in ethanol (2.0 ml) as described for isoflav-3-ene-4 ', 7-diol. Performance: (0.04g, 60%). XH NMR (CDC13 + d6_DMS0): d 4.94 (s, 2H, H2), 6.21 (d, ÍH, J 2.0 Hz, H8), 6.29 (dd, ÍH, J 2.3 Hz, 8.3 Hz, H6), 6.62 (m , HH, ArH), 6.64 (bs, 1H, H), 6.75-6.82 (m, 3H, ArH), 7.07 (t, 1H, J 7.9 Hz, ArH), 8.99-9.17 (bs, 2H, OH).

Example 40 3'-Methoxysoflav-3-ene-7-ol 3 '-Metoxylsoflav-3-ene-7-ol was prepared from 7-acetoxy-3' -methoxyisoflav-3-ene (O.lg, 0.3 mmol ) and imidazole (0.15g) in ethanol (2.0 ml) as described for isoflav-3-ene-4 ', 7-diol. Yield: (0.06g, 70%) m.p. 75 ° C. 1N NMR (CDCl 3): d 3.84 (s, 3H, OMe), 5.12 (s, 2H, H2), 6.38 (d, ÍH, J 2.0 Hz, H8), 6.40 (dd, ÍH, J 2.0 Hz, 8.3 Hz , H6), 6.76 (bs, ÍH, H4), 6.84 (dd, ÍH, J 1.9 Hz, 8.3 Hz, ArH), 6.95 (m, 3H, ArH), 7.29 (t, 1H, J 8.3 Hz, ArH) .

Example 41 3'-Methoxysoxy lav-3-ene- ', 7-dxol 3'-Methoxylsoflav-3-ene-4', 7-diol was prepared from 4 ', 7-diacetoxy-3-methoxyisoflav-3- eno (O.llg, 0.3 mmol) and imidazole (0.3g) in ethanol (2.0 ml) as described for isoflav-3-ene- ', 7-diol. Yield: (O.Oßg, 71%). XH NMR (deacetone): d 3.90 (s, 3H, OMe), 5.07 (s, 2H, H2), 6.31 (d, ÍH, J 2.3 Hz, H8), 6.40 (dd, ÍH, J 2.3 Hz, 8.3 Hz , H6), 6.78 (bs, 1H, H4), 6.83 (d, IH, J 8.3 Hz, ArH), 6.92 (d, 2H, J 1.9 Hz, 8.3 Hz, ArH), 7.14 (d, IH J 1.9 Hz , ArH), 7.04, 7.63 (each s, ÍH, OH).

Example 42 Isoflav-3-ene-7-ol Isoflav-3-ene-7-ol was prepared from 7-acetoxyisoflav-3-ene (0.2g, 0.75 mmole) and imidazole (0.24g) in ethanol (3.5 ml) as described for isoflav-3-ene-4 ', 7-diol. Yield: (O.llg, 66%) m.p. 120 ° C. XH NMR (d6-DMSO): d 5.07 (s, 2H, H2), 6.24 (d, ÍH, J 2.2 Hz, H8), 6.33 (dd, ÍH, J 1.9 Hz, 7.9 Hz, H6), 6.96 (d, ÍH, J 7.9 Hz, H5), 7.00 (s, ÍH, H4), 7.26-7.47 (m, 5H, ArH), 9.65 (bs, ÍH, OH). Mass spectrum: m / z 224 (m, 74%); 223 (100), 175 (28); 165 (23); 147 (41).

Example 43 Iso lav-3-ene-4 ', 7, 8-triol Imidazole (0.6g) was added to a suspension of 4,7,8-triacetoxyisoflav-3-ene (O.ldg, 0.4 mmol) in absolute ethanol (5.0 ml) and the mixture was refluxed for 45 minutes under argon. The solution it was concentrated under reduced pressure and the product was precipitated by the addition of distilled water (10 ml). The mixture was left overnight in the refrigerator and filtered to provide isoflav-3-ene. The crude product was recrystallized from methanol / benzene to give Isofla v-3-ene-4 '/ 7-8-triol (0.08 g, 75%). 1 NMR (CDC13 + d6_DMSO): d 4.97 (s, 2H, H2), 6.30 (d, ÍH, J 8.2 Hz, H6), 6.36 (d, ÍH, J 8.3 Hz, H5), 6.55 (bs, 1H, H4), 6.72 (d, ÍH, J 8.7 Hz, ArH), 7.17 (d, 2H, J 8.7 Hz, ArH).

Example 44 4'-Methoxyisoflav-3-ene-7,8-diol 4'-Methoxyisoflav-3-ene-7,8-diol was prepared from 7,8-diacetoxy-4-methoxyisoflav-3-ene (0.15 g, 0.4 mmole) and imidazole (0.4 g) in ethanol (1.6 ml) as described for isoflav-3-ene-4 ', 7-8-triol.

Yield: (0.73g, 61% LH NMR (CDC13 + d6_DMS0) 3. 83 (s, 3H, OCH3), 5.15 (s, 2H, H2), 6.51 (d, ÍH, J 8.3 Hz, H6), 6.58 (d, ÍH, J 8.3 Hz, H5), 6.68 (bs, ÍH, H4), 6.92 (d, ÍH, J 8.7 Hz, ArH), 7.35 (d, 2H, J 8.7 Hz, ArH). Mass spectrum: m / z 270 (M, 5%); 256 (100); 255 (70); 239 (20); 181 (25).

Example 45 8-Methylisoflav-3-ene-4 ', 7-dxol Imidazole (0.6 g) was added to a suspension of 4', 7-diacetoxy-8-methylisoflav-3-ene (0.25 g, 0. 7 mmol) in absolute ethanol (5.0 ml) and the mixture was refluxed for 45 minutes under argon. The solution was concentrated under reduced pressure and the product was precipitated by the addition of distilled water (10 ml). The mixture was left overnight in the refrigerator and filtered to provide isoflav-3-ene. The crude product was recrystallized from methanol / benzene to give 8-methylisoflav-3-ene-4 ', 7-diol (0.13g, 68%). P.f. 190 ° C-93 ° C. XH NMR (CDC13 + d6_DMS0): d 1.94 (s, 3H, CH3), 4.98 (s, 2H, H2), 6.32 (d, ÍH, J 7.9 Hz, H6), 6.58 (bs, ÍH, H4), 6.67 (bd, ÍH, H5), 6.72 (d, 2H, J 8.7 Hz, ArH), 7.21 (bd, 2H, ArH). Mass spectrum: m / z 255 (M + 1, 16%); 254 (M, 79); 253 (100); 161 (32).

Example 46 8-Methylisoflav-3-ene-3 ', 7-diol 8-Methylisoflav-3-ene-3', 7-diol was prepared from 3 ', 7-diacetoxy-8-methylisoflav-3-ene ( 0.12g, 0.4 mmol) and imidazole (0.3g) in ethanol (2.5 ml) as described for 8-methylisoflav-3-ene-4 ', 7-diol. Yield: (0.07g, 77%) p.f. 130 ° C. XH NMR (CDC13 + d6_DMSO): d 1.95 (s, 3H, CH3), 4.98 (s, 2H, H2), 6.34 (d, ÍH, J 8.0 Hz, H6), 6.61-6.94 (m, 5H, ArH) , 7.08 (bt, ÍH, ArH). Mass spectrum: m / z 254 (M, 100%); 253 (96); 161 (45).

Example 47 4 '-Metoxx-8-methylisoflav-3-ene-7-ol 4' -Metoxy-8-methylisoflav-3-ene-7-ol was prepared from 7-acetoxy-4 '-methoxy-8- methylisoflav-3-ene (O.llg, 0.3 mmol) and imidazole (0.14g) in ethanol (1.5 ml) as described for 8-methylisoflav-3-ene-4 ', 7-diol. Yield: (0.05 g, 53%) m.p. 103 ° C. XH NMR (d6-acetone): d 1.99 (s, 3H, CH3), 3.81 (s, 3H, OMe), 5.11 (s, 2H, H2), 6.43 (d, OH, J 8.3 Hz, H6), 6.77 (bs, ÍH, H4), 6.80 (d, ÍH, J 8.3 Hz, H5), 6.95 (d, 2H, J 9.0 Hz, ArH), 7.44 (d, 2H, J 9.0 Hz, ArH). Mass spectrum: 282 (M, 9%); 267 (100); 268 (95); 134 (52).

Example 48 3'-Methoxy-8-methylisoflav-3-ene-4 ', 7-diol 3' -Metoxy-8-methylisoflav-3-ene-4 ', 7-diol was prepared from 4', 7- diacetoxy-3 '-methoxy-8-methylisoflav-3-ene (0.21g, 0.6 mmol) and imidazole (0"52g) in ethanol (4 ml) as described for 8-methylisoflav-3-ene-4', 7 -diol. Yield: (O.lg, 63%). 1H NMR (CDC13): d 2.14 (s, 3H, CH3), 3.94 (s, 3H, OMe), 5.11 (s, 2H, H2), 6.42 (d, 1H, J 8.3 Hz, H6), 6.64 (bs , HH, ArH), 6.80 (d, 1H, J 7.9 Hz, ArH), 6.94 (m, 2H, ArH), 7.12 (m, HH, ArH), 7.26, 7.70 (each bs, HH, OH).

Deprotection Reactions Example 49 cis- and t-trans-tetrahydrodaxdzexna Imidazole (0.2 g) was added to a suspension of 1,3-diacetoxytetrahydrodaidzein (0.10 g, 0.3 mmol) in absolute ethanol (4.0 ml) and the mixture was brought to reflux for 45 minutes under argon. The solution was concentrated under reduced pressure and distilled water (10 ml) was added. The mixture was left overnight in the refrigerator and the crystalline product was filtered to provide cis- and trans-tetrahydrodaidzein (0.06 g, 80%).

Example 50 Trans-Tetrahydrodaidzein (trans-4 ', 7-Dihydroxyisoflavan-4-ol) Trans-4', 7-dihydroxyisoflavan-4-ol was prepared from trans-4 ', 7-dihydroxyisoflavan-4-ol and imidazole in ethanol as described for cis-and trans-tetrahydrodaidzein. 1 H NMR (d6-acetone): d 2.99 (ddd, ΔH, J 3.4 Hz, 6.8 Hz, 10.6 Hz, H3), 4.13 (dd / 1H, J 7.0 Hz, 10.9 Hz, H2); 4.24 (dd, ÍH, J 3.8 Hz, 11.3 Hz, H2), 4.70 (d, ÍH, J 6.4 Hz, H4), 6.20 (d, 1H, J 2.6 Hz, H8), 6.38 (dd, ÍH, J 2.3 Hz, 8.3 Hz, H6), 6.71 (d, 2H, J 8.7 Hz, ArH), 7.04 (d, 2H, J 8.7 Hz, ArH), 7.18 (d, ÍH, J 8.3 Hz, H5).

Example 51 cis- and fcrans-7-Hydroxy-4'-methoxyisoflavan-4-ol Imidazole (0.4 g) was added to a suspension of 7-acetoxy-4'-methoxyisoflavan-4-ol (0.20 g, 0.6 mmol) in absolute ethanol (8.0 ml) and the mixture was refluxed for 45 minutes under argon. The solution was concentrated under reduced pressure and distilled water (10 ml) was added. The mixture was left overnight in the refrigerator and the crystalline product was filtered to provide ci s- and trans-7-hydroxy-4'-methoxyisoflavan-4-ol (0.16g, 79%).

Example 52 cis- and trans-7-Hydroxyisoflavan-4-ol 7-hydroxyisoflavan-4-ol was prepared from 7-acetoxyisoflavan-4-ol (0.14g, 0.5 mmol) and Imidazole (0.17g) in ethanol (3.0 ml) as described for cis- and trans-tetrahydrodaidzein. For trans-7-hydroxyisoflavan-4-ol; XH NMR (d6-acetone): d 3.08 (m, H, H3), 4.00 (t, H, J, 10.2 Hz, H2); 4.30 (m, HH, H2), 4.81 (d, HH, J 7.2 Hz, H4), 6.25-6.43 (m, ArH), 6.89 (d, J 8.3 Hz, ArH), 7.07 (d, J 8.3 Hz, ArH), 7.22-7.64 (m, ArH). For cis-7-acetoxyisoflavan-4-ol; H NMR (d6-acetone): d 3.20 (m, H, H3), 4.36 (m, H, H2); 4.57 (dd, ÍH, J 10.2 Hz, 12.0 Hz, H2), 4.68 (bs, ÍH, H4), 6.25-6.43 (m, ArH), 6.89 (d, J 8.3 Hz, ArH), 7.07 (d, J 8.3 Hz, ArH), 7.22-7.64 (m, ArH).

Example 53 cis- and traps-4 ', 7-Dihydroxy-8-methylisoflavan-4-ol 4', 7-Dihydroxy-8-methylisoflavan-4-ol was prepared from 4 ', 7 ~ diacetoxy-8-methylisisoflavan -4-ol (0.4g, 1.1 mmol) and imidazole (l.Og) in ethanol (7.0 ml) as described for cis- and trans-tetrahydrodaidzein. For trans-4 ', 7-dihydroxy-8-methylisoflavan-4-ol; XH NMR (de-acetone): d 1.98 (s, 3H, CH3), 2.98 (ddd, ΔH, J 3.8 Hz, 10.9 Hz, 12.0 Hz, H3), 4.18 (m, ΔH, H2); 4.27 (m, ÍH, H2), 4.75 (d, ÍH, J 6.4 Hz, H4), 6.42 (m, ArH), 6.75 (m, ArH), 7.05-7.19 (m, ArH), 7.66 (bs, OH ). For cis-4 ', 7-dihydroxy-8-methylisoflavan-4-ol; XH NMR (d6-acetone): d 1.99 (s, 3H, CH3), 3.01 (dt, ÍH, J 3.4 Hz, 12.0 Hz, H3), 4.31 (m, ÍH, H2); 4.52 (dd, ÍH, J 10.2 Hz, 12.0 Hz, H2), 4.60 (bs, ÍH, H4), 6.42 (m, ArH), 6.75 (m, ArH), 7.05-7.19 (m, ArH), 7.66 ( bs, OH).

Example 54: traps-7-Hydroxy-4'-methoxy-8-methyliso lane-4-ol Trans-7-Hydroxy-4'-methoxy-8-methylisoflavan-4-ol was prepared from trans-7-acetoxy- 4'-methoxy-8-methylisoflavan-4-ol (0.23g, 0.7 mmol) and imidazole (0.28g) in ethanol (2.1 ml) as described for cis- and trans-tetrahydrodaidzein. P.f. 162 ° C.

Mass spectrum: 285 M, 5%); 268 (10); 151 (20); 135 (twenty); 134 (100); 119 (20). XH NMR (d6 ~ acetone): d 1.97 (s, 3H, CH3), 3.00 (ddd, ÍH, J 3.4 Hz, 7.2 Hz, 10.2 Hz, H3), 3.72 (s, 3H, OMe), 4.20 (dd, ÍH, J 7.5 Hz, 10.9 Hz, H2); 4.27 (m, HH, H2), 4.73 (d, HH, J6.8 Hz, H4), 6.45 (d, HH, J 8.3 Hz, H6), 6.85 (d, 2H, J 8.6 Hz, ArH), 7.10 ( d, ÍH, J 8.7 Hz, H5), 7.18 (d, 2H, J 8.6 Hz, ArH).

Hydrogenation reactions: -Isof lavona cxs Isof lavender-4-ol Example 55 cis-4 ', 7-Diacetoxyisoflavan-4-ol Platinum (IV) oxide (Adam's catalyst) (0.05 g) was added to a solution of 4', 7-diacetoxyisoflavanone (0.25 g) , 0.7 mmol) in ethyl acetate (40 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 55 hours. The catalyst was removed by filtration through Celite and the filtrate was evaporated in vacuo to provide predominantly cis-4 ', 7-diacetoxyisoflavan-4-ol. For cis-4 ', 7-diacetoxyisoflavan-4-ol; 1H NMR (CDC13): d 2.28 (s, 3H, OCOCH3), 2.29 (s, 3H, OCOCH3), 3.30 (dt, ÍH, J 3.4 Hz, J 11.8 Hz, H3), 4.31 (ddd, ÍH, J 1.4 Hz, 3.6 Hz, 10.5 Hz, H2); 4.56 (dd, ÍH, J 10.5 Hz, 11.8 Hz, H2), 4.75 (dd, ÍH, J 1.3 Hz, 3.2 Hz, H4), 6.66 (dd, ÍH, J 2.3 Hz, 8.7 Hz, H6), 6.69 ( d, ÍH, J 2.3 Hz, H8), 7.08 (d, 2H, J 8.6 Hz, ArH), 7.26 (d, ÍH, 8.4 Hz, H5), 7.29 (d, 2H, J 8.6 Hz, ArH). 13 C NMR (CDCl 3): d 20.98 (OCOCH 3), 43.52 (C3), 64.10 (C2), 66.46 (C4), 110.08 (C6), 114.09 (C8), 121.82, 129.40 (ArCH), 131.10 (C5).

Hydrogenation reactions: -Isof lavone - * > Isoflavan-4 -one Example 56 4 ', 7-Diacetoxydihydrodaxdzein (41,7-Diacetoxyisoflavan-4-one) Palladium on charcoal (5%, 0. 02g) to a solution of 4 ', 7-diacetoxidadzein (0.50 g, 1.5 mmol) in ethyl acetate (80 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 72 hours. The catalyst was removed by filtration through Celite and the resulting filtrate was evaporated in vacuo. The residue was recrystallized from ethanol to provide 4 ', 7-diacetoxydihydrodaidzein (0.40 g, 80%) as colorless plates. XH NMR (CDC13): d 2.29 (s, 3H, OCOCH3), 2.23 (s, 3H, OCOCH3), 3.98 (dd, ÍH, J 6.2 Hz, 8.2 Hz, H3), 4.69 (m, 2H, H2), 6.78-6.82 (m, 2H, ArH), 7.08 (d, 2H, J 9.2 Hz, ArH), 7.30 (d, 2H, J 8.2 Hz, ArH), 7.98 (d, 1H, J 9.2 Hz H5).

Hydrogenation reactions: -Isof wash-3-ene - ^ Isoflavan Example 57 O, O-Diacetylequol Palladium on charcoal (5%, 0. 02g) to a solution of 4 ', 7-diacetoxyisoflav-3-ene (0.20g, 0.06 ml) in ethyl acetate (60 ml) and the mixture was stirred at room temperature under a hydrogen atmosphere for 24 hours. The catalyst was removed by filtration through Celite and the resulting filtrate was evaporated in vacuo. The residue was recrystallized from dichloromethane / light petroleum to provide 0.0-diacetylequinol (0.15g, 75%). XH NMR (CDC13): d 2.29 (s, 3H, OCOCH3), 2.31 (s, 3H, 0C0CH3), 3.00 (d, 2H, J 8.3 Hz, H4), 3.25 (m, 1H, H3), 4.00 (t, ÍH, H2), 4.34 (dd, ÍH, J 3.4 Hz, 10.9 Hz, H2), 6.61 (d, J 7.5 Hz, ÍH, ArH), 6.60 (s, ÍH, ArH), 7.06 (bd, 3H, J 8.3 Hz, ArH), 7.24 (d, 3H, J 8.3 Hz, ArH).

Deprotection reactions Example 58 Dihydrodaidzein (4 ', 7-Dihydroxyisoflavan-4-one) Imidazole (0.63 g) was added to a suspension of 4', 7-diacetoxydihydrodaidzein (0.26 g, 0.08 mmol) in absolute ethanol (5.0 ml) and The mixture was refluxed for 45 minutes under argon. The solution was concentrated under reduced pressure and distilled water (10 ml) was added to the residue. The mixture was left overnight in the refrigerator and the resulting precipitate was filtered. The crude product was recrystallized from ethyl acetate / dichloromethane to provide 4 ', 7-diacetoxydihydrodaidzein (0.14g, 71%) as a white powder. H NMR (d6-acetone): d 3.83 (t, 1H, J 7.2 Hz, H3), 4.60 (d, 2H, J 6.2 Hz, 112), 6.39 (d, ÍH, J 2.0 Hz, H8), 6.55 (dd, ÍH, J 8.2, J 2.0 Hz, ArH), 6.80 (d, 2H, J 8.2 Hz, ArH), 7.10 (d, 1H, J 8.2 Hz, ArH), 7.74 (d , 1H, J 8.2 Hz, H5).

Example 59 Equol (4 ', 7-Dihydroxyisoflavane) Imidazole (0.5g) was added to a suspension of O, O-diacetylequinol (0.15g, 0.08 mmol) in absolute ethanol (5.0 ml) and the mixture was refluxed for 45 minutes. minutes under argon. The solution was concentrated under reduced pressure and distilled water (10 ml) was added to the residue. The mixture was left overnight in the refrigerator and the resulting product was filtered to provide equol (0.09g, 80%) as a white powder. H NMR (d6-DMSO): d 2.70 (d, 2H, J 9.2 Hz, H4), 2.92 (m, H, H3), 3.73 (t, H, J 10.3 Hz, H2), 4.06 (d,, H, J 3.0 Hz, 11.2 Hz, H2), 6.16 (bs, ÍH, ArH), 6.21 (bd, J 8.2 Hz, ÍH, ArH), 6.63 (d, 2H, J 8.2 Hz, ArH), 6.69 (d, ÍH , J 8.2 Hz, ArH), 6.87 (d, 2H, J 8.2 Hz, ArH) Those skilled in the art will appreciate that the invention described herein is susceptible to variations and modifications other than those specifically described. It should be understood that the invention includes all these variations and modifications. The invention also includes all steps, features, compositions and compounds related or indicated in the specification, individually or collectively, and any and all combinations of any of two or more of the steps or features mentioned.

Claims (46)

1. NOVELTY OF THE INVENTION Having described the present invention, it is considered as a novelty and, therefore, the content of the following CLAIMS is claimed as property: 1. A method for the preparation of a compound of the formula II wherein i / R2 R3 / R5 e, R7 and Rs are independently hydrogen, hydroxy, ORg, OC (0) R9, OS (0) R9, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino , nitro or halo, and R9 is alkyl, haloalkyl, aryl, arylalkyl or alkylaryl, which comprises the step of hydrogenating a compound of the formula I where i / R2 / R3 / R4 / R5 R1 / R7 / Rs and R9 are as defined above to prepare a compound of formula II. The method according to claim 1, wherein the hydrogenation step is carried out with hydrogen in the presence of a reduction catalyst and a solvent. The method according to claim 2, wherein the reduction catalyst comprises palladium, palladium hydroxide, platinum or platinum oxide. 4. The method according to claim 3, wherein the reduction catalyst is palladium on activated carbon, palladium on barium sulfate or platinum (IV) oxide. The method according to claim 4, wherein the reduction catalyst is palladium on activated carbon (1% Pd for 10% Pd). 6. The method according to claim 5, wherein the reduction catalyst is palladium of about 5% on activated carbon. The method according to claim 2, wherein the solvent is a Ci-Cs alcohol, an alkyl acetate or a C? ~ C3 carboxylic acid. The method according to claim 7, wherein the solvent is a methanol, ethanol or alkyl acetate of Ci-Ce-9. The method according to claim 8, wherein the solvent is absolute methanol or absolute ethanol. 10. The method according to claim 1, further comprising the step of dehydrating and deprotecting or optionally transforming a compound of the formula II to prepare a compound of the formula III Ri / R2 R3 R Rs / ß / R7 and Rs are independently hydrogen, hydroxy, OR9, OC (0) R9, OS (0) R9, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino, nitro or halo, and R9 is alkyl, haloalkyl, aryl, arylalkyl or alkylaryl. The method according to any of claims 1 to 10, wherein the compounds of the formulas I, II or III have the following substituents Ri is hydroxy, OR9 or OC (0) R9, R2, R3, R4, R5, R6 and R7 are independently hydrogen, hydroxy, ORg, OC (O) R9, alkyl, aryl or arylalkyl, Rs is hydrogen, and R9 is methyl, ethyl, propyl, isopropyl or trifluoromethyl. 12. The method according to claim 11, wherein the compounds of the formulas I, II or III have the following substituents Ri is hydroxy, ORg or OC (0) R9, R2J 3 / R 5 and R7 are independently hydrogen, hydroxy, ORg, OC (0) R9, alkyl, aryl or arylalkyl, R6 and Rs are hydrogen, and R9 is methyl. The method according to any of claims 1 to 12, wherein the compound of the formula I is 4 ', 7-diacetoxyisoflavone (daidzein diacetate) or 7-acetoxy-1-methoxyisoflavone. The method according to any of claims 1 to 13, wherein the compound of formula II is 4 ', 7-diacetoxyisoflavan-4-ol (tetrahydrodaidzein diacetate) or 7-acetoxy-4' -methoxyisoflavan-4-ol . The method according to any of claims 10 to 14, wherein the compound of the formula III is 4 ', 7-diacetoxyisoflav-3-ene (dehydroequol diacetate), 4', 7-dihydroxyisoflav-3-ene (dehydroequol) ), 7-acetoxy-4 '-methoxyisoflav-3-ene or 7-hydroxy-4' -methoxyisoflav-3-ene. 16. A method for the preparation of a compound of the formula IV wherein Ri / R2 / 3/4 Rs Rβ7 and d are independently hydrogen, hydroxy, OR9, OC (0) R9, OS (O) R9, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino, dialkylamino , nitro or halo, and R9 is alkyl, haloalkyl, aryl, arylalkyl or alkylaryl, which comprises the step of hydrogenating a compound of the formula I wherein Ri R2 / 3 / R4 R5 / R7 R7 Rs and R9 are as defined above to prepare a compound of the formula IV. The method according to claim 16, wherein the hydrogenation step is carried out with hydrogen in the presence of a reduction catalyst and a solvent. 18. The method according to claim 17, wherein the reduction catalyst comprises palladium, palladium hydroxide, platinum or platinum (IV) oxide. The method according to claim 18, wherein the reduction catalyst is palladium on activated carbon (1% Pd at 10% Pd). The method according to claim 19, wherein the reduction catalyst is palladium of about 5% on activated carbon. 21. The method according to claim 17, wherein the solvent is a C? -C8 alcohol / an Ci-Cg alkyl acetate or a C? -C3 carboxylic acid. 22. The method according to claim 21, wherein the solvent is absolute methanol, ethanol or ethyl acetate. 23. The method according to any of claims 16 to 22, wherein the compound of formula I is 4 ', 7-diacetoxyisoflavone (daidzein diacetate) or 7-acetoxy-4' -methoxyisoflavone. The method according to any of claims 16 to 22, wherein the compound of formula IV has the following substituents Ri is hydroxy, 0R9 or OC (0) R9, R2, R3, R4, Rs, Re and R7 are independently hydrogen, hydroxy, OR9, OC (0) Rg, alkyl, aryl or arylalkyl, Rs is hydrogen, and R9 is methyl, ethyl, propyl, isopropyl or trifluoromethyl. The method according to claim 24, wherein the compound of formula IV has the following substituents R, is hydroxy, 0R9 or OC (0) R9, R2 / R3 / R4 Rs and R7 are independently hydrogen, hydroxy, OR9, 0C (0) R9, alkyl, aryl or arylalkyl, Re and Rs are hydrogen, and Rg is methyl. 26. The method according to claim 25, wherein the compound of the formula IV is 4 ', 7-diacetoxyisoflavan-4-one (diacetoxydihydrodaidzein) or 4', 7-dihydroxyisoflavan-4-one (dihydrodaidzein). 27. A method for the preparation of a compound of the formula V wherein Ri / 2 R3, R4 5 / ß / 7 and Re are independently hydrogen, hydroxy, OR9, OC (0) R9, OS (O) R9, alkyl, haloalkyl, aryl, arylalkyl, thio, alkylthio, amino, alkylamino , dialkylamino, nitro or halo, and R9 is alkyl, haloalkyl, aryl, arylalkyl or alkylaryl, comprising the step of hydrogenating a compound of formula III wherein Ri R2 R3 / 4 R5 ß / R7 Rs and R9 are as defined above to prepare a compound of formula V. 28. The method according to claim 27, wherein the hydrogenation step is carried out with hydrogen in the presence of a reduction catalyst and a solvent. 29. The method according to claim 28, wherein the reduction catalyst comprises palladium, palladium hydroxide, platinum or platinum (IV) oxide. 30. The method according to claim 29, wherein the reduction catalyst is palladium on activated carbon (1% Pd for 10% Pd). 31. The method according to claim 30, wherein the reduction catalyst is palladium of about 5% on activated carbon. 32. The method according to claim 28, wherein the solvent is a C? -C8 alcohol, an Ci-C? Alkyl acetate or a C? ~ C3 carboxylic acid. 33. The method according to claim 32, wherein the solvent is a methanol, ethanol or ethyl acetate. 34. The method according to claim 33, wherein the solvent is ethyl acetate. 35. The method according to any of claims 27 to 34, wherein the compound of formula III is 4 ', 7-diacetoxyisoflav-3-ene (dehydroequol diacetate), 4', 7-dihydroxyisoflav-3-ene (dehydroequol) ), 7-acetoxy-4 '-methoxyisoflav-3-ene or 7-hydroxy-4' -methoxyisoflav-3-ene. 36. The method according to any of claims 27 to 34, wherein the compound of the formula V has the following substituents Ri is hydroxy, OR9 or OC (0) R9, R2 / R3 / R4 Rs / Re and R7 are independently hydrogen, hydroxy, OR9, OC (0) Rg, alkyl , aryl or arylalkyl, R8 is hydrogen, and Rg is methyl, ethyl, propyl, isopropyl or trifluoromethyl. 37. The method according to claim 36, wherein the compound of formula V has the following substituents Ri is hydroxy, 0R9 or 0C (0) R9, R2, R3, R4, R5 and R7 are independently hydrogen, hydroxy, 0R9, 0C (0) R9, alkyl, aryl or arylalkyl, Re and R8 are hydrogen, and Rg is methyl. 38. The method according to claim 37, wherein the compound of the formula V is 4 ', 7-diacetoxyisoflavan (equol diacetate) or 4', 7-dihydroxyisoflavan (equol). 39. The methods practically as herein described especially with reference to the Examples. 40. The compounds of formula II or formula III or formula IV or formula V when prepared by a method according to any of the preceding claims. 41. A compound of the formulas II, III, IV or V, wherein Ri is hydroxy, ORg, 0C (0) R9, thio, alkylthio or halo, R2 / R3 R4 s Re R7 and Rd are independently hydrogen, hydroxy, OR9, 0C (0) R9, OS (O) R9, alkyl, aryl, thio, alkylthio or halo, and Rg is alkyl, fluoroalkyl or arylalkyl with the proviso that at least one of R5, R5 and R7 is not hydrogen, or when R5, R6 and R are all hydrogen, then R3 is hydroxy, ORg, OC (O) R9, OS (0) R9, alkyl, aryl, thio , alkylthio or halo with the proviso that the compounds of the formula Ri is hydroxy or acetoxy, R 2 is hydrogen, hydroxy, acetoxy, methoxy, methyl, isopropyl or halo, R 3 is hydrogen, methoxy, methyl, halo trifluoromethyl, R6 is hydrogen, hydroxy or acetoxy, and R7 is hydrogen, hydroxy, methyl or methoxy are specifically excluded, with the proviso that the compounds of the formula wherein R3 is hydroxy or methoxy, and R is hydrogen or methoxy are specifically excluded, with the proviso that the compounds of the formulas wherein Ri is hydroxy, methoxy, ethoxy, methylthio or halogen, and R2, R3, R4, R5, R6 and R7 are independently hydrogen, hydroxy, methoxy, ethoxy, methylthio or halogen, are specifically excluded, and with the proviso that the compounds 4 ', 7-Dihydroxy-3', 5'-dimethoxyisoflavan-4-one 4 'f 5-dimethoxy-7-hydroxy-8-methylisoflavan-4-one 2', 7-dihydroxy- 4 ', 8' -dimetoxiisoflavan-4-ene are specifically excluded. A compound according to claim 41, wherein Ri is hydroxy, OR9 or OC (O) Rg, R2 and R3 are independently hydrogen, hydroxy, ORg or OC (O) R9, R, R5, Re, and Re are hydrogen, R7 is hydroxy, ORg, OC (0) R9, alkyl, aryl or halo, and R9 is methyl, ethyl, propyl, isopropyl, trifluoromethyl or benzyl. 43. A compound according to claim 41, wherein Ri is hydroxy, 0R9 or OC (0) R9, R2 and R are independently hydrogen, hydroxy, ORg or OC (0) Rg, R5 is OR9, 0C (0) R9, alkyl, aryl or halo, R 4, R 6, R 7, and R 8 are hydrogen, and R g is methyl, ethyl, propyl, isopropyl, trifluoromethyl or benzyl. 44. A compound of formula I selected from the group consisting of: ', 7, 8-Triacetoxyisoflavone 7,8-Diacetoxy-4' -methoxyisoflavone 4 ', 7-Diacetoxy-8-methylisoflavone 3', 7-Diacetoxy-8 -methyl isoflavone 7-Acetoxy-4-t-methoxy-8-methyl-isoflavone 4", 7-Diacetoxy-3 '-methoxy-8-methylisoflavone 4', 5, 7-Triacetoxyisoflavone 45. A compound of formula II selected from the group consisting of: 4 ', 7, 8-Triacetoxyisoflavan-4-ol 7,8-Diacetoxy-4-methoxyisoflavan-4-ol', 7-Diacetoxy-8-methylisoflavan-4- ol 3 ', 7-Diacetoxy-8-methylisoflavan-4-ol 7-Acetoxy-4' -methoxy-8-methylisoflavan-4-ol 4 ', 7-Diacetoxy-3' -methoxy-8-methylisoflavan-4-ol 4 ', 5, 7-Triacetoxiisoflavan-4-ol 4 ', 7, 8- Rihydroxyisoflavan-4-ol 7, 8-Dihydroxy-4-methoxyisoflavan- -o1 4', 7-Dihydroxy-8-methylisoflavan-4-ol 3 ', 7-Dihydroxy-8-methylisoflavan-4 -ol 7-Hydroxy-4 '-methoxy-8-methylisoflavan-4-ol 4', 7-Dihydroxy-3 '-methoxy-8-methylisoflavan-4-ol 4', 5, 7-Trihydroxyisoflavan-4-ol 46. A compound of formula III selected from the group consisting of: 4 ', 7, 8-Triacetoxydehydroequol (4', 7, 8-Triacetoxyisoflav-3-ene) 7,8-Diacetoxy-4-methoxideshydroequol (7,8-Diacetoxy) -4-methoxyisofla -3-ene) ', 7-Diacetoxy-8-methylisoflav-3-ene 3', 7-Diacetoxy-8-methylisoflav-3-ene 7-Acetoxy-4 '-methoxy-8-methylisoflav-3 -ne 4 ', 7-Diacetoxy-3' -methoxy-8-methylisoflav-3-ene 4 ', 5, 7-Triacetoxyisoflav-3-ene Isoflav-3-ene-4', 7,8-triol 4 '- Methoxyisoflav-3-ene-7, 8-diol 8 -Methylisoflav-3-ene-4 ', 7 -diol 8-Methylisoflav-3-ene-3', 7 -diol 4 '-Metoxy-8 -methyl-isoflav-3- eno-7-ol 3 '-Metoxy-8-methylisoflav-3-ene-4', 7-diol Isoflav-3-ene-4 ', 5,7-triol.