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

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