Xanthohumol Pyrazole Derivative Improves Diet-Induced Obesity and Induces Energy Expenditure in High-Fat Diet-Fed Mice.

The energy intake exceeding energy expenditure (EE) results in a positive energy balance, leading to storage of excess energy and weight gain. Here, we investigate the potential of a newly synthesized compound as an inducer of EE for the management of diet-induced obesity and insulin resistance. Xanthohumol (XN), a prenylated flavonoid from hops, was used as a precursor for the synthesis of a pyrazole derivative tested for its properties on high-fat diet (HFD)-induced metabolic impairments.

Reductive Metabolism of Xanthohumol and 8-Prenylnaringenin by the Intestinal Bacterium Eubacterium ramulus.

Scope: The intestinal microbiota transforms a wide range of available substrates, including polyphenols. Microbial catabolites of polyphenols can contribute in significant ways to the health-promoting properties of their parent polyphenols. This work aims to identify intestinal metabolites of xanthohumol (XN), a prenylated flavonoid found in hops (Humulus lupulus) and beer, as well as to identify pathways of metabolism of XN in the gut.

Total synthesis of [ C] -, [ C] -, and [ C] -isotopomers of xanthohumol, the principal prenylflavonoid from hops.

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.