Hyperforin chemical structure

The chemical structure of hyperforin has been deduced by spectroscopic means, as well as by chemical degradation and derivatization [45,46]. This lipophilic component of St. John s Wort consists of a mixture of photo- and oxygen-sensitive tautomers. Hyperforin is also unstable toward high temperature, on prolonged storage and in solution [9]. In particular, it has been shown that the compound is stable in protic solvents and unstable in apolar solvents such as n-hexane. It degrades at 40°C in presence of air [47,48]. 

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

They resemble hyperforin in their chemical structure, having in addition a 2,2-dimcthyl-2//-pyran ring, most probably derived by the cyclization of a 3-methylbut-2-enyl side chain with an enolic hydroxyl group. Only a few reports describe a similar natural tricyclic system [59-60]. 

Phytochemical studies of different species of Hypericum indicated that the genus is a valuable source of secondary metabolites, with peculiar chemical features. Several other prenylated phloroglucinols, not related to hyperforin and sometimes unique in their structure, have been identified in II. drummondii [53],//. brasiliense [54], and//, japonicum [55],... 

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. 

The structure of hyperforin 10 was determined with extensive chemical degradation and derivatisation, as well as with spectroscopic means. Bystrov and co-workers described the isolation of 10 and systematically deduced its general chemical and physico-chemical characteristics [34, 35, 36, 37, 38] and suggested its stereochemistry [39, 40]. An acetone extract of St. John Wort was chromatographed over silica gel with gradient elution by petroleum ether-benzene mixtures. Further purification was performed by converting hyperforin 10 into the crystalline 3,5-dinitrobenzoate 11, from which the pure compound 10 was obtained by alcali hydrolysis. The molecular formula of hyperforin 10 was established by elemental analysis and mass spectrometry. From the IR-spectrum, the... 

The relative stereochemistry of 10 was described by Brondz et al. [41] based on X-ray data of the 3,5-dinitrobenzoic acid ester of 10. The same group finally published the absolute configuration of hyperforin 10 from single crystal X-ray analysis of its p-brombenzoic acid ester 17 [42]. As the structure of hyperforin 10 was elucidated primarily on the basis of chemical degradation, attempts to prove its structure by complete synthesis have failed [43]. 

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