Chemistry of heteroanalogs of isoflavones 14. Isoxazole analogs of isoflavones

Isoxazole analogs of isoflavones have been synthesized by the cyclization of -(3-isoxazolyl)-2-hydroxyacetophenones. Their alkylation, acylation, and electrophilic substitution reactions, and reactions with binucleophiles have been studied. 3-(3-Isoxazolyl)-7-methoxychromones are rearranged selectively into 2-aminochromone derivatives by the action of hydroxylamine as a result of a double recyclization and are recyclized into pyrazole derivatives by hydrazine. Preparations with hypolipidemic, anabolic, hypoglycemic, and antiarrhythmic action are found among the derivatives of 3-(3-isoxazolyl)chromones.For Communication 13, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 29–39, January, 1993.     

Chemistry of heteroanalogs of isoflavones

Thiazole analogs of isomeric isoflavones were synthesized from -(2,4-dimethyl-5-thiazolyl)-2-hydroxyacetophenones, and their reaction with hydrazine hydrate and alkylating and acylating agents was studied. The reaction of thiazole derivatives of 7-hydroxychromone with hydrazine hydrate proceeds with opening of the pyrone ring and subsequent cyclization of the intermediate to o-hydroxyphenylpyrazole derivatives. The reaction of hydrazine hydrate with thiazole derivatives of 5-hydroxychromone, which proceeds with retention of the pyrone ring, leads to hydrazones. The structures of the new compounds were confirmed by the PMR spectra.See [1] for communication 6.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 1, pp. 25–28, January, 1979.     

Synthesis and properties of heterocyclic analogs of isoflavones

The condensation of cyanomethyl derivatives of furan and benzofuran with di- and trihydric phenols has given the corresponding 2,4-dihydroxy- and 2,4,6-trihydroxy--heterylacetophenones. The latter have been converted by reaction with acid anhydride, ethoxalyl chloride, and trifluoroacetic anhydride into 3-heterylchromones with methyl, trifluoromethyl, and ethoxycarbonyl groups in position 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1202–1208, September, 1973.     

Chemistry of heteroanalogs of isoflavones. 23. Synthesis of aminoacyl derivatives of 3-phenoxychromone

Reaction of Boc-protected amino acids with 3-phenoxy-2-trifluoromethylchromones gave new, previously unknown aminoacyl derivatives.T. G. Shevchenko Kiev University, Kiev 252033, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 6, pp. 744–748, June, 1999.     

Chemistry of heteroanalogs of isoflavones. 8. Reaction of benzofuran analogs of isoflavones and their 4-thioxo derivatives with hydroxylamine and hydrazine

A number of 3-(2-benzofuryl)-6-ethylchromones and their 4-thioxo derivatives were synthesized, and the action of hydroxylamine and hydrazine on them was investigated. Isomeric 3 (5)-(o-hydroxyphenyl) isoxazoles were obtained in the reaction with hydroxylamine. The predominant formation of one or the other isomer depends on the character of the substituents in the 2 and 4 positions of the chromone. The reaction of chromones with hydrazine leads to o-hydroxyphenylpyrazoles. The compounds obtained were characterized by their IR, UV, and PME spectra.See [ 1] for Communication 7.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 892–897, July, 1981.     

Chemistry of heteroanalogs of isoflavones

It is shown that treatment of 3-hetarylchromones with alkalis and hydrazine hydrate leads to opening of the pyrone ring and subsequent conversion of the intermediate to -hetaryl-2-hydroxyacetophenones and 2-hydroxyphenylpyrazole derivatives.See [1] for communication IV.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1474–1476, November, 1976.     

Chemistry of heteroanalogs of isoflavones

Condensation of cyanomethyl derivatives of benzimidazole and benzothiazole with resorcinol gave the corresponding 2,4-dihydroxy-α-hetarylacetophenones. The latter were converted to 3-hetarylchromones with methyl, trifluoromethyl, and ethoxycarbonyl groups in the 2 position or to chromones without substituents in this position.     

Analysis of isoflavones in foods and dietary supplements

Isoflavones are phytochemicals found in many plants. Because of their structural similarity to beta-estradiol, health benefits of isoflavones have been evaluated in age-related and hormone-dependent diseases. Daidzein, genistein, and glycitein are present as free forms or derivatives in foods containing soy or soy protein extracts. The analysis of isoflavones has become more complex, because preparations contain isoflavones from multiple sources (e.g., red clover, kudzu). Red clover contains primarily formononetin and biochanin A, while kudzu extracts, which are becoming increasingly common in dietary supplements, contain puerarin and daidzein, among other components. Isoflavones are present in foods and dietary supplements as free compounds, glucoside derivatives, 6"-O-malonyl-7-O-beta-D-glucoside derivatives, and 6"-O-acetyl-7-O-beta-D-glucoside derivatives. High-performance liquid chromatography (HPLC)/tandem mass spectrometry has been applied to the identification of isoflavone derivatives based on the fragmentation pattern of the parent ion, providing high selectivity and sensitivity in the quantitation of isoflavones in complex mixtures. HPLC with ultraviolet detection is often chosen for routine analysis, but a preliminary acid or basic hydrolysis of isoflavone derivatives is often required for the investigation of samples containing extracts from multiple sources. Several internal standards have been used in the analysis of isoflavones from a single botanical source (e.g., soy, red clover), but the identification of a general internal standard remains a challenging process.     

Chemistry of the hetero analogs of isoflavones. 22. Mannich reaction in the benzimidazole and benzothiazole analogs of isoflavones

New 3-(2-benzothiazolyl)chromones were obtained by the reaction of 2-(2,4-dihydroxy-5-ethylphenacyl)-benzothiazole with triethyl orthoformate or carboxylic acid anhydrides. Aminomethylation of the chromones and also of familiar 3-(2-benzimidazolyl)chromones by substituted 1,1-diaminomethanes gave Mannich bases.For Communication 21, see [1].Taras Shevchenko Kiev University, Kiev, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1072–1078, August, 1998.     

Ultrasound-assisted extraction of soy isoflavones

Efficiency in extracting four isoflavone derivatives (daidzin, glycitin, genistin and malonyl genistin) from freeze-dried ground soybeans was compared for mix-stirring extraction and ultrasound-assisted extraction, using different solvents and extraction temperatures with both. The efficiency of the extraction of soy isoflavones was improved by ultrasound but was dependent on the solvent employed. Optimization of the ratios of sample quantity to solvent volume and length of extraction time was also performed. Isoflavones can be quantitatively extracted from soybeans with 50% ethanol at 60 degrees C using ultrasound-assisted extraction in 20 min.     

Chemistry of isoflavone heterocyclic analogs. 10. Synthesis of pyrimidines by recyclization of isoflavones and their heterocyclic analogs

Isoflavones and their thiazole and pyrazole analogs are recyclized into the corresponding 4-(2-hydroxyphenyl)-pyrimidine derivatives under the effect of amidines. Their PMR spectra were studied. The effects related to the formation and strength of the intramolecular hydrogen bond were examined.For Communication 9, see [1].Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, pp. 1542–1550, November, 1985.     

Chemistry of heteroanalogs of isoflavones. 16. Benzthiazole analogs of isoflavones

The reaction of a-(2-benzthiazolyl)-2, 4-dihydroxy-5-alkylacetophenones with anhydrides and chlorides of carboxylic acids yielded 3-(2-benzthiazolyl)chromones with electron-acceptor and electron-donor substituents, as well as chromones unsubstituted in the 2 -position. Their acylation, alkylation, and aminoacylation reactions and their interaction with electrophilic and nucleophilic reagents were studied.Taras Shevchenko Kiev University, Kiev 252017. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 464–471, April, 1994. Original article submitted March 5, 1994.     

Chemistry of heteroanalogs of isoflavones

Pyrazole analogs of isoflavones were synthesized from substituted -(4-pyrazolyl)-2,4-dihydroxyacetophenones.See [1] for communication III.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 8, pp. 1108–1111, August, 1976.     

Chemistry of the heteroanalogs of isoflavones. 20. Benzimidazole analogs of isoflavones

3-(2-Benzimidazolyl)chromones with electron-donating and electron-withdrawing substituents and also chromones unsubstituted at position 2 were obtained by the reaction of alkyl--(2-benzimidazolyl)-2,4-dihydroxy-5-acetophenones with carboxylic acid anhydrides and chlorides. Reactions with cleavage and with retention of the pyrone ring were carried out.For Communication 19, see [1].Taras Shevchenko Kiev University, Kiev. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1237–1244, September, 1997.     

Synthetic and modified isoflavonoids XV. Interaction of synthetic analogs of isoflavones with hydrazine hydrate and its derivatives

The reactions of 1,3-benzodioxolane, 1,4-benzodioxane, and 1,5-benzodioxepane analogs of isoflavones with hydrazine derivatives have been studied. It has been found that under the action of hydrazines the new isoflavones recyclize into 3,4-diarylpyrazones. Their structures have been confirmed by their PMR spectra.Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 629–633, September–October, 1994.     

Chemistry of modified flavonoids. XVIII. Thiazole analogs of isoflavones. Homologous and isomeric series

Homologous and isomeric series of thiazole derivatives of isoflavones were produced on the basis of -(4-methyl-2-thiazolyl)-2-hydroxyacetophenones. A study of -(4-methyl-2-thiazoyl)-2-hydroxyacetophenones by PMR spectroscopy showed that these compounds exist in most nonpolar and low polarity organic solvents exclusively in the ketone form, but in dimethyl sulfoxide solution both the ketone and enol forms are observed in various ratios. A simple and effective preparative method of synthesis of homologs of 3-(2-diazolyl)-chromones was developed, and their alkylation at the phenolic hydroxyl was studied. Data of biological tests of the compounds synthesized are presented.For communication 17, see [1].T. G. Shevchenko Kiev University, Kiev 252601. Translated from Khimiya Geterotsikiicheskikh Soedinenii, No. 4, pp. 505–513, April, 1995. Original article submitted March 19, 1995.     

Pressurized liquid extraction of isoflavones from soybeans

Isoflavone derivatives from freeze-dried soybeans were extracted by pressurized liquid extraction (PLE) and determined by reverse-phase high performance liquid chromatography (HPLC) with both photo diode array and mass spectrometry (MS) detection. Both real and spiked samples were used in the development of the method.Several extraction solvents (methanol (MeOH) and ethanol (EtOH), 30-80% in water and water), temperatures (60-200 °C), pressures (100-200 atm), as well as the sample size (0.5-0.05 g) and cycle length (5-10 min) were studied for the optimization of the extraction protocol. The optimized extraction conditions for quantitative recoveries were: 0.1 g of sample, 100 °C, three (7 min) static extraction cycles and ethanol 70% as extracting solvent. The stability of the isoflavones during the PLE was also determined. Under PLE conditions, degradation of malonyl glucoside forms of the isoflavones takes place using temperatures higher than 100 °C whereas degradation of glucosides takes place above 150 °C. Using the optimized protocol, isoflavones can be extracted from freeze-dried soybeans without degradation.     

Synthetic and modified isoflavonoids XVII. Interaction of synthetic analogs of isoflavones with guanidine

Under the influence of guanidine, 1,3-benzodioxolane, 1,4-benzodioxane, and 1,5-benzodioxepane analogs of isoflavone are converted into 2-aminopyrimidine derivatives     

Purines. XIV. Synthesis and properties of 8-nitroxanthine and its N-methyl derivatives

Xanthine ( 1 ) and its N-methyl derivatives 2–16 have been nitrated to the corresponding 8-nitro derivatives 17–32 under different reaction conditions. Nitration in glacial acetic acid with nitric acid works well with the N-7 unsubstituted and some of the 9-methylxanthines, respectively, whereas the 7-methylxanthine derivatives react best with nitronium tetrafluoroborate in sulfolane or glacial acetic acid. The 8-nitro group can be displaced nucleophilically to form 8-chloro-, 33, 34 , 8-ethoxy-, 35,36 , and uric acid derivatives 37–40 , respectively. The newly synthesized 8-nitroxanthines have been characterized by elemental analyses, pK-determinations and uv and ¹H-nmr spectra.     

Use of lanthanide shift reagents for studying pyridine analogs of isoflavones

The interaction of lanthanide shift reagents (LSR) with pyridine analogs of isoflavone and their derivatives has been studied. It was found that the pyridine nitrogen atom can increase the coordinating ability of electron donor groups in the molecule, in particular the sulfur atom in chromone thiones. It has been shown that LSR interact actively with pyridinium methylsulfate salts containing the 3-chromone substituent. The efficiency of the coordination is influenced by the occurrence of steric hindrance around the chromone carbonyl. The structure of the adducts of these salts with LSR is discussed.Taras Shevchenko University, Kiev 252033, Ukraine. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 3, pp. 342–345, March, 1998.