A New Approach to Synthesis of Isoflavonoids Having Boneresorption Activity

异黄酮类化合物是一组具有共同的1，2-二苯基丙烷骨架的氧杂环。近年来，有关异黄酮类化合物生物活性的报道越来越多。最近，从异黄酮类化合物香豆素开发的一种药物已经商业化，作为治疗骨质疏松症的治疗剂，这是一种老年人的疾病。作者认为，异黄酮类化合物的结构如此多样化，尚未被开发为更有前途的骨吸收抑制药的来源。由于异黄酮类化合物一直没有被公认为是合成化学的研究对象，所以很少有广泛应用的合成方法。在这种情况下，作者开发了以下异黄酮类化合物的合成新方法：(1)三硝酸铊直接转化为异黄酮类化合物在强酸性介质中与三硝酸铊处理黄烷酮引起重排…更多的2-芳基在一步中提供相应的异黄酮类。由于黄烷酮很容易从相应查尔酮的酸催化环化反应中获得，该反应将是各种异黄酮类的一种简便的合成工具。3-芳基香豆素-3-芳基香豆素类化合物的合成新方法3-芳基香豆素类化合物也是由欧米隆-羟基苯甲醛和苯乙酸的羟醛缩合而成的一类易得的异黄酮衍生物。提出了一种将3-芳基香豆素的α-吡喃环转化为呋喃的新方法。利用该方案合成了几种天然的2-芳基苯并呋喃。(3)异黄酮类化合物的新合成方法3-芳基香豆素的α-吡喃环被二氯铝氢化物还原，在不引起开环的情况下产生相应的异叶片。异黄酮烯的催化加氢提供异黄酮类化合物。利用该化学方案制备了几种异黄酮类化合物，并对其进行了骨吸收抑制实验。较少

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