Synthesis of the [2H]-labelled urinary lignans, enterolactone and enterodiol, and the phytoestrogen daidzein and its metabolites equol and O-demethyl-angolensin

Abstract

Methods are described for the synthesis of [²H₆]enterolactone, {[²H₆]-trans-2,3-bis(3-hydroxybenzyl)-γ-butyrolactone}, [²H₆]enterodiol, {[²H₆]-2,3-bis(3-hydroxybenzyl)butane-1,4-diol}, [²H₄]daidzein, {[²H₄]-7-hydroxy-3-(4-hydroxyphenyl)-4H-1-benzopyran-4-one}, [²H₄]equol, {[²H₄]-3(4-hydroxyphenyl)-2H-1-benzopyran-7-ol}, and [²H₅]-O-demethylangolensin,{[²H₆]-1-(2′,4′-dihydroxy-2-(p-hydroxyphenyl)propiophenone} by hydrogen–deuterium exchange at aromatic rings using PBr₃ or NaOD in deuterium oxide or labelled trifluoroacetic acid. The structures, isotopic purities and positions of uptake of deuterium were determined by n.m.r. and mass spectrometry (m.s.)