Studies towards the enantioselective synthesis of 3-Hydroxyisoflavanones and derivatives with potential estrogenic action

Isoflavanones (like Cajanol and Isodalparvinol) are secondary metabolites mostly found in legumes. They have been described as phytoestrogens and may be used in the treatment of hormone related diseases like breast cancer and osteoporosis. The asymmetric synthesis of 3-hydroxyisoflavanones is limited by the employment of benzoin reaction catalyzed by chiral carbenes, but showing a small substrate scope. We have envisioned an enantioselective synthetic strategy through a chiral cyanohydrin intermediate, which can be obtained through a variety of methods. There is a report of a racemic version, but only one 3-hydroxyisoflavanone was prepared through this approach and no yield was mentioned. First, the racemic methodology is under study using commercial available substrates whose were submitted to the O-alkylation, subsequent cyanosilylation and a cyclization in acidic or basic media to afford the correspondent 3-hydroxyisoflavanone. Studies on the substrate scope and the enantiomeric preparation of the cyanohydrin of this approach are ongoing.