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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 13C-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-[13C]2-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-[13C]-2′,4′-bis(benzyloxymethyloxy)-6′-methoxy-3′-(3-methylbuten-2-yl)acetophenone and 1′-[13C]-4-(methoxymethyloxy)benzaldehyde. The 13C-atom in the methyl ketone was derived from 1-[13C]-acetyl chloride while that in the aryl aldehyde was derived from [13C]-iodomethane. Tri- and penta-13C-labeled xanthohumols were similarly prepared by applying minor modifications to the route. [ABSTRACT FROM AUTHOR]

A generalized method for accessing highly functionalized amino-substituted bicyclo[2.2.2]octanes via p-dodecylphenylsulfonamide catalyst in a good enantio- and diastereoselective fashion has been developed. A discussion of the mechanistic underpinnings of this transformation is presented. Finally, an unexpected discovery enabling the extension of this protocol to the synthesis of OH-substituted bicyclo[2.2.2]octanes with encouraging levels of stereoselectivity is discussed. [ABSTRACT FROM AUTHOR]

Drugs exert desired and undesired effects based on theirbindinginteractions with protein target(s) and off-target(s), providing evidencefor drug efficacy and toxicity. Pioglitazone and rosiglitazone possessa common functional core, glitazone, which is considered a privilegedscaffold upon which to build a drug selective for a given targetinthis case, PPARγ. Herein, we report a retrospective analysisof two variants of the glitazone scaffold, pioglitazone and rosiglitazone,in an effort to identify off-target binding events in the rat heartto explain recently reported cardiovascular risk associated with thesedrugs. Our results suggest that glitazone has affinity for dehydrogenases,consistent with known binding preferences for related rhodanine cores.Both drugs bound ion channels and modulators, with implications incongestive heart failure, arrhythmia, and peripheral edema. Additionalproteins involved in glucose homeostasis, synaptic transduction, andmitochondrial energy production were detected and potentially contributeto drug efficacy and cardiotoxicity. [ABSTRACT FROM AUTHOR]