Synthesis of Various Kinds of Isoflavones, Isoflavanes, and Biphenyl-Ketones and Their 1,1-Diphenyl-2-picrylhydrazyl Radical-Scavenging Activities

• Published in: Chemical & pharmaceutical bulletin Vol. 57; no. 4; pp. 346 - 360
• Main Authors: Goto, Hideyuki, Terao, Yoshiyasu, Akai, Shuji
• Format: Journal Article
• Language: English
• Published: TOKYO The Pharmaceutical Society of Japan 01.04.2009; Pharmaceutical Soc Japan; Japan Science and Technology Agency
• Subjects: Biphenyl Compounds - chemical synthesis; Biphenyl Compounds - chemistry; Biphenyl Compounds - pharmacokinetics; Chemistry; Chemistry, Medicinal; Chemistry, Multidisciplinary; Flavonoids - chemical synthesis; Flavonoids - chemistry; Flavonoids - pharmacology; Free Radical Scavengers - chemical synthesis; Free Radical Scavengers - chemistry; Free Radical Scavengers - pharmacology; isoflavane; isoflavone; Isoflavones - chemical synthesis; Isoflavones - chemistry; Isoflavones - pharmacology; Ketones - chemical synthesis; Ketones - chemistry; Ketones - pharmacology; Life Sciences & Biomedicine; metabolite; Molecular Structure; Pharmacology & Pharmacy; Physical Sciences; Picrates - chemical synthesis; Picrates - chemistry; Picrates - pharmacokinetics; radical scavenging activity; Science & Technology; soybean; soybean; METABOLITES; FLAVONOIDS; isoflavane; IDENTIFICATION; POTENT INHIBITORS; GLYCITEIN; isoflavone; IN-VITRO; POLYPHENOLS; metabolite; DAIDZEIN; SOY ISOFLAVONES; radical scavenging activity; CONSTITUENTS
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.57.346

Forty-eight kinds of isoflavones (8), thirty-one isoflavanes (9), and forty-seven biphenyl-ketones (10, 10′) were synthesized from eleven kinds of substituted phenols (11) and six phenylacetic acids (12). Among them, seventy-five compounds are new. The radical scavenging activities of these compounds were evaluated using 1,1-diphenyl-2-picrylhydrazyl (DPPH) at pH 6.0. We found that thirty-nine out of forty-three compounds having a catechol moiety on either the A- or the B-ring exhibited a high activity (ED50=12—54 μM) similar to that of catechin. In these cases, the remaining part of their structure seemed to have little effect on their activity. Many 6- or 8-hydroxyisoflavanes (9E—I) and their biphenyl-ketone derivatives (10E—H) also showed a high activity (ED50=<50 μM), while all of their corresponding isoflavones (8E—I) were not active at all. The 7-hydroxyisoflavanes having either an additional hydroxyl group at the C5-position (9D) or a methoxy group at the C6-position (9J) presented a high activity (ED50=26—32 μM). This study suggests that natural isoflavones have the possibilities of exhibiting antioxidant activities through the hydroxylation at the C6-, C8-, or C3′-position or the formation of the isoflavanes (9) and/or the biphenyl-ketone derivatives (10′) by metabolism or biotransformation.