A New Approach to Synthesis of Isoflavonoids Having Boneresorption Activity

具有骨吸收活性的异黄酮类化合物的合成新方法

• 批准号: 05671767
• 负责人: KINOSHITA Takeshi
• 金额: $ 1.28万
• 依托单位: Faculty of Pharmceutical Sciences Teikyo University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05671767/
• 关键词: Isoflavonoid; Isoflavones; 2-Arylbenzofurans; Isoflavans; Synthesis; Bone-resorption inhibition; アリル転移反応; 2-アリルベンゾフラン

The isoflavonoids are a group of oxygen heterocycles having a common 1,2-diphenylpropane skeleton. In recent years there have been an increasing number of reports referring to biological activities of isoflavonoids. Quite recently, a medicinal drug that was developed from an isoflavonoid lead coumestrol has been commercialized as a therapeutic agent for the treatment of osteoporosis, the diseases of the aged. The author considered that the isoflavonoids, structurally so diverse, have yet to be exploited as the source of more promising bone-resorption inhibitory agents. Since the isoflavonoids have not been recognized as the attractive subject for synthetic chemistry, there have been few synthetic methods of wide scope. These circumstances led the author to develop the following new synthetic methods of isoflavonoids.(1) Direct conversion of flavanones into isoflavones by thallium trinitrateTreatment of flavanones with thallium trinitrate under strong acidic medium caused rearrangement … More of the 2-aryl group furnishing corresponding isoflavones in one step. Since flavanones are readily available from acid-catalized cyclisation of corresponding chalcones, this reaction will be of value as a facile synthetic tool of various isoflavones. Using this method the author successfully synthesized isoflavones with various substituents including halogens.(2) A new synthetic approach to 2-arylbenzofurans via ring contraction of 3-arylcoumarins3-Arylcoumarins are also a group of isoflavonoid derivatives readily available form aldol condensation of omicron-hydroxybenzaldehydes and phenylacetic acids. The author developed a new method to convert the alpha-pyrone ring of 3-arylcoumarins into furan. By use of this scheme several naturally occurring 2-arylbenzofurans were synthesized.(3) A new synthetic approach to isoflavansThe alpha-pyrone ring of 3-arylcoumarins was successfully reduced by dichloroaluminium hydride to give rise to corresponding isoflavenes without causing ring opening. Catalytic hydrogenation of the resulting isoflavenes furnished isoflavans. Several isoflavans were prepared using this chemical scheme.The isoflavonoids prepared as stated above were subjected to bone-resorption inhibition assay. Less

异黄酮类化合物是一组氧杂环化合物，具有共同的1,2-二苯丙烷骨架。近年来，有关异黄酮生物活性的报道越来越多。最近，一种由异黄酮类铅库米雌醇开发的药物已被商业化，作为治疗骨质疏松症的治疗剂，老年人的疾病。作者认为，由于异黄酮在结构上的多样性，作为更有前途的骨吸收抑制剂的来源还有待开发。由于异黄酮还没有被公认为是合成化学的一个有吸引力的主题，因此很少有广泛的合成方法。在这种情况下，作者开发了以下几种合成异黄酮的新方法。(1)用三硝酸铊直接将黄酮转化为异黄酮用三硝酸铊在强酸性介质中处理黄酮时，可使更多的2-芳基在一步中提供相应的异黄酮。由于黄酮很容易从相应的查尔酮的酸催化环化中得到，因此该反应将作为各种异黄酮的简便合成工具而具有价值。用这种方法成功地合成了含卤素等不同取代基的异黄酮。(2) 3-芳基香豆素环缩法合成2-芳基苯并呋喃的新方法。3-芳基香豆素也是一组易于通过羟苯甲醛和苯乙酸醛醇缩合而得到的类异黄酮衍生物。本文提出了一种将3-芳基香豆素α -吡酮环转化为呋喃的新方法。利用该方案合成了几种天然存在的2-芳基苯并呋喃。(3)异黄酮合成的新途径用二氯氢化铝成功还原了3-芳基香豆素的α -吡酮环，得到了相应的异黄酮而不引起开环。催化加氢得到的异黄酮为异黄酮。用这种化学方法制备了几种异黄酮。用上述方法制备的异黄酮进行骨吸收抑制实验。少

项目成果

木下武司: "硝酸タリウム(III)によるフラバノンの環縮小反応について" 日本薬学会第115年会講演要旨集. (1995)

Takeshi Kinoshita：“关于硝酸铊(III) 的黄烷酮环还原反应”日本药学会第 115 届年会摘要（1995 年）。

T.Kinoshita: "Ring Contraction of Flavanone Heterocycles with Thallium trinitrate" Abstract papers of 115th Annual Meeting of the Pharmaceutical Society of Japan (Sendai). (1995)

T.Kinoshita：“黄烷酮杂环与三硝酸铊的环收缩”日本药学会（仙台）第 115 届年会摘要论文。

木下武司、市瀬浩志、三川 潮: "骨吸収抑制作用を有するイソフラボノイドの新規合成法" 第25回複素環化学討論会講演要旨集. 235-238 (1994)

Takeshi Kinoshita、Hiroshi Ichise、Ushio Mikawa：“具有骨吸收抑制作用的异黄酮类化合物的新合成方法”第25届杂环化学研讨会摘要235-238（1994）。

T.Kinoshita, K.Ichinose, U.Sanakawa: "A New Approach to the Synthesis of Isoflavonoids with Bone-resorption Inhibitive Activity" Abstract papers of 25th Congress of Heterocyclic Chemistry (Tokyo). 235-238 (1994)

T.Kinoshita、K.Ichinose、U.Sanakawa：“具有骨吸收抑制活性的异黄酮类合成新方法”第 25 届杂环化学大会（东京）摘要论文。