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

杂环是一组具有共同的1，2-二苯基丙烷骨架的氧杂环。近年来，关于其生物活性的报道越来越多。最近，从一种可药用的铅香豆雌酚开发的药物已经商业化，作为治疗骨质疏松症、老年人疾病的治疗剂。作者认为，结构如此多样的骨钙素尚未被开发为更有前途的骨吸收抑制剂的来源。由于化合物还没有被认为是合成化学中有吸引力的主题，因此很少有广泛的合成方法。这些情况促使作者开发了以下新的合成方法。(1)三硝酸铊直接将黄烷酮转化为二氢黄酮--在强酸性条件下用三硝酸铊处理黄烷酮引起重排反应 ...更多信息 在一个步骤中，2-芳基提供相应的双氢吡喃酮。由于黄烷酮容易从相应的查耳酮的酸催化环化反应中获得，因此该反应将作为各种异黄酮的简易合成工具具有价值。利用这种方法，作者成功地合成了包括卤素在内的各种取代基的甾酮。(2)3-芳基香豆素缩环合成2-芳基苯并呋喃的新方法3-芳基香豆素也是一组可通过对羟基苯甲醛与苯乙酸的羟醛缩合反应得到的香豆素衍生物。作者发展了一种将3-芳基香豆素的α-吡喃酮环转化为呋喃的新方法。通过使用该方案，合成了几种天然存在的2-芳基苯并呋喃。(3)异黄烷合成的新方法用氢化二氯铝成功地还原了3-芳基香豆素的α-吡喃酮环，得到了相应的异黄烷。所得异黄烯的催化氢化提供异黄烷。用这种化学方案制备了几种骨聚糖，对如上所述制备的骨聚糖进行骨吸收抑制试验。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。