The synthesis of [3,4,1′‐13C3]genistein

A facile synthesis is described for 3,4,1′‐¹³C₃]genistein for use as an internal standard in isoflavone analysis by mass spectrometric methods. Ethyl 4‐hydroxy1‐¹³C]benzoate was first prepared from the reaction of diethyl 2‐¹³C]malonate and 4H‐pyran‐4‐one. Two further ¹³C atoms were incorporated using potassium ¹³C]cyanide as the source to give 4′‐benzyloxy‐1,2,1′‐¹³C₃]phenylacetonitrile. 3,4,1′‐¹³C₃]Genistein was then constructed through coupling of the isotopically labelled phenylacetonitrile with phloroglucinol under Hoesch conditions, followed by formylation and cyclization. Copyright © 2007 John Wiley & Sons, Ltd.