Hyperforin is an antibiotic, antibacterial, antiprotozoal, antiviral, anticancer, and immunomodulatory substance. It is possibly a new and potent tool for curative treatment of a broad array of infection diseases. Despite the medical usefulness of Hypericum perforatum L., which has been known since ancient times, its constituents were not well studied until the middle of the 20th century. Several pharmacological active substances (PASs) were then discovered as constituents of H. perforatum. Among these was the antibacterial substance, hyperforin. The chemistry and relative and absolute stereochemistry of hyperforin were studied at the Shemyakin Institute of Bioorganic Chemistry, USSR Academy of Sciences, Moscow, USSR, the Institute of Biochemistry and Physiology of Microorganisms, USSR Academy of Sciences, Moscow, USSR, and the Zabolotny Institute of Microbiology and Virology at the Ukrainian Academy of Sciences, Kiev, UkrSSR. In this paper, hyperforin’s relative and absolute stereochemistry, as reported in earlier published former USSR literature (cited herein), is discussed, as well as cited up to date in international literature. In 1979, the relative and absolute stereochemistry of hyperforin and some constituents of H. perforatum were studied at the University of Oslo, Oslo, Norway. In 1979, Brondz et al. challenged the correctness of the relative and absolute stereochemistry of hyperforin reported previously by Bystrov et al. The relative stereochemistry of a drug is the basis for possible partial or total synthesis and absolute stereochemistry is crucial for the action of drugs on enzymes. Correct molecular isometry (absolute stereochemistry) is key for high pharmacological activity versus harm/toxicity. Elucidation of the ste-reochemistry of an unknown molecule is of great academic and theoretical interest, and in the case of a drug, it also has great practical interest.
Evidence and knowledge of the medical value of Hypericum perforatum L.1 in ancient times are contained in the writings of Galen, Dioscorides, Pliny, and Hippocrates. In the middle of the 20th century, Osborn published a review [
In 1975, Bystrov et al. [
As mentioned in the Introduction, the pharmacological usefulness of H. perforatum has been described by Galen, Dioscorides, Pliny, and Hippocrates. The usefulness of H. perforatum in the Middle Ages has also been reported. More recently, in the middle of the 20th century, antibacterial properties of the drug were considered [
In the very early days of scientific chemistry, several important criteria were established for elucidation of the chemistry of unknown molecules: atom composition (qualitative and quantitative), molecular weight (MW), structure, and stereochemistry. As ultimate evidence for the correct elucidation of the chemistry and stereochemistry of an unknown molecule was the synthesis of a substance that complied with the nature of the molecule under investigation. A correct hypothesis about the structure was accepted also based on X-ray crystallography. However, the last word in confirming correctness was left to the de novo synthesis of the unknown molecule and comparison of its nature with the molecule under investigation. Only if all parameters of the unknown molecule and the synthetically prepared analog are in compliance, and the identity of the two molecules is established, can the structure of the unknown molecule, be claimed as known. This is especially important in the case of isomeric molecules and molecules with chirality. Partial degradation of a molecule that is under investigation and spectral comparison with known molecules can lead to errors because the degradation can affect the chirality of the resulting substance in relation to the chirality of the molecule under investigation. Here, it is important to note that R and S chirality has no direct reflection on or relation with the + or − signs: “… the (+)/(−) system has no fixed relationship with the (R)/(S) system” [
According to Bystrov et al. [
In [
Following the logic of the numbering presented by Bystrov et al. in [
C-7 and C-8 as R and S, respectively. Concerning the chirality of C-5, there exists many conflicting explanations. It is nonetheless possible to extract the conclusion that the authors designated it as 5S-spiro[4,4]-nonane-1,6-dione, which means that C-5 has chirality S. However, following the IUPAC rules for this structure presented in [
Upon inspection of [
in the bicyclic system is confusing, and the C-1 and C-5 positions were exchanged. For this reason, it could be expected that the chirality was also ch- anged. However, it was overall not possible to comment confidently on the chirality of these carbons because the numbering of the carbon atoms compromised the relative chemistry of this substance [
In 1978, the same team published further information [
The same team of authors was responsible for [
hyperforin is incorrect. The value of the other publications by Bystrov et al. describing the determination of the relative and absolute stereochemistry of hyperforin is very limited, and this literature cannot be recommended as a basis for scientific work. Attempts to present Bystrov et al. as the discoverer of the relative and absolute stereochemistry of hyperforin in Wikipedia and in other publications at the expense of other authors are not ethical, and do not give prestige to the former USSR Academy of Sciences or to Wikipedia. This issue reflects the fact that Wikipedia is missing an Editor-in-Chief and qualified editorial staff.
Brondz, I. (2017) Super Antibiotics: Part III. Hyperforin, Revision of the Relative and Absolute Stereochemistry Presented by Bystrov et al. Voice of the Publisher, 3, 15-24. https://doi.org/10.4236/vp.2017.32002