A New Approach to Synthesis of Isoflavonoids Having Boneresorption Activity

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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