Hyperforin oxidation

Fig. (7). Chemical structure of hyperforin oxidative degradation products.

J.-L. Wolfender, L. Verotta, L. Belvisi, N. Fuzzati, and K. Hostettmann, Structural investigation of isomeric oxidized forms of hyperforin by HPLC-NMR and WLC-MS", Phytochem. Anal. 14 (2003), 290-297. 

COMT hypothesis. According to this hypothesis. St. John s wort increases the levels of catecholamines at the brain synapses by inhibiting their inactivation by oxidative deamination (MAOl) and by catechol functionalization (catechol-0-methyltransferase [COMTl). Recent studies have shown that hypericins possess such activities only at pharmacologically excessive concentrations. If true, these effects at normal doses are small and do nothing to alleviate depression. Other hypotheses suggest hormonal effects or effects on the dopaminergic system. Hyperforin has become a candidate for the major antidepressant constituent of St. John s wort. 

In the recent years, a number of analogues more polar than hyperforin have been characterized in II. perforatum [50-52]. Due to the limited stability of hyperforin(s), the question rises however, whether those compounds are genuine metabolites or artifacts produced during the isolation and purification procedures. Figure (7) illustrates some of the oxidative degradation products of hyperforin which have been isolated from St. John s Wort. 

Methyl-3-buten-2-ol, a component of St. John s Wort essential oil, is also reported as a degradative product possibly obtained by oxidative cleavage of the isoprenyl side chain of hyperforin and adyhyperforin [9]. 

In a specific work, it has been shown that chemical modification of hyperforin by acylation, oxidation and alkylation produce detrimental effects on the molecule activity as inhibitor of serotonin uptake [89], and the presence of the enolized cyclohexanedione moiety in its structure has been related to its efficacy on the re-uptake of neurotransmitters. 

A nitrile oxide tethered to an allene, generated in situ, midergoes an intramolecular cycloaddition reaction to generate a key intermediate in the synthesis of hyperforins. ... 

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