Synthesis and labeling of isoflavone phytoestrogens, including daidzein and genistein.

Abstract

The synthesis of the important diphenolic isoflavone type phytoestrogens starting from the corresponding unprotected phenols and arylacetic acids is discussed. The aryl rings may carry additional alkyl, methoxy, and/or halogeno groups. Intermediate polyhydroxy deoxybenzoins can also be isolated in good yield. Isotopically labeled isoflavone phytoestrogens were prepared for use as internal standards in ion exchange chromatography and GC-MS selected ion monitoring (SIM technique). Traditional methods rely on total synthesis using deuterated starting materials for the preparation of labeled isoflavonoid structures. We have used successfully an application where the H/D exchange is performed within the finished molecular framework, based on the exchange of aromatic protons that are ortho or para to a phenolic OH group. By this method the deuterated products are available in an isotopic purity of 90% or higher.