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; 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

异黄素是一组具有1,2-二苯基丙烷骨架的氧杂环。近年来，越来越多的报告指的是异黄素的生物学活动。最近，一种是由异类球体铅香豆酚开发的药物，已被商业化为治疗骨质疏松症的治疗剂，即老年人的疾病。作者认为，在结构上如此潜水的异黄素尚未被探讨为更有承诺的骨吸抑制剂的来源。由于异黄素尚未被认为是合成化学的有吸引力的主题，因此很少有合成范围的合成方法。这些情况导致作者开发了以下新的异黄酮合成方法。（1）通过在强酸性培养基下的thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium thallium artrangement下，黄酮酮直接转换为异黄酮植物，引起了thallium thallium thallium thallium thallium coprangement，这会导致2- ARYL组提供的相应的相应的异洛夫酮。由于亚麻酮可以从相应的chalcone的酸催化的环化中获得，因此该反应将作为各种异黄酮的便捷合成工具具有价值。使用这种方法，作者成功合成了具有包括卤素在内的各种亚物质的异黄酮。（2）通过3-芳基藻素的环收缩3-芳基芳族3-芳香蛋白的环的新合成方法是一组异黄酮类衍生物的形成型emyllyshysymysylyshy，也可用酸。作者开发了一种新方法，将3-芳香蛋白的Alpha-Pyrone环转换为Furan。通过使用该方案，合成了几种天然存在的2-芳替四呋喃。（3）一种用于异黄素的新合成方法，用于3-芳基甲蛋白的α-吡喃环酮环通过二氯亚氨基烷成功降低，而水力水则可以使相应的异氟烷基产生，而无需引起环。所得的异黄酮提供异黄素的催化氢化。使用这种化学方案制备了几种异黄素。如上所述制备的异黄素进行了骨吸附抑制测定。较少的