Linus Pauling Institute

Xanthohumol [(E)-6'-methoxy-3'-(3-methylbuten-2-yl)-2',4',4″-trihydroxychalcone], he principal prenylated flavonoid from hops, has a complex bioactivity profile, and C-labeled isotopomers of this compound are of potential use as molecular probes and as analytical standards to study metabolism and mode of action. 1,3-[ C] -Xanthohumol was prepared by an adaptation of the total synthesis of Khupse and Erhardt in 7 steps and 5.7% overall yield from phloroglucinol by a route incorporating a cascade Claisen-Cope rearrangement to install the 3'-prenyl moiety from a 5'-prenyl aryl ether and an aldol condensation between 1-[ C]-2',4'-bis(benzyloxymethyloxy)-6'-methoxy-3'-(3-methylbuten-2-yl)acetophenone and 1'-[ C]-4-(methoxymethyloxy)benzaldehyde. The C-atom in the methyl ketone was derived from 1-[ C]-acetyl chloride while that in the aryl aldehyde was derived from [ C]-iodomethane. Tri- and penta- C-labeled xanthohumols were similarly prepared by applying minor modifications to the route.