Super Antibiotics: Part III. Hyperforin, Revision of the Relative and Absolute Stereochemistry Presented by Bystrov &amp;lt;i&amp;gt;et al&amp;lt;/i&amp;gt;.

Ilia Brondz

doi:10.4236/vp.2017.32002

Abstract

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.

Highlights

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 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
In 1975, Bystrov et al [6] described the structure of hyperforin, which is the principal pharmacological active substance (PAS) in H. perforatum

Summary

Introduction

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 1975, Bystrov et al [6] described the structure of hyperforin, which is the principal pharmacological active substance (PAS) in H. perforatum. In 1975, Bystrov et al reported that the PAS in H. perforatum is hyperforin, and they further described hyperforin’s structure and the stereochemistry (Figure 1) [6]. In their following publications about the stereochemistry of antibiotic hyperforin [10] and [11], the authors of [6] changed the numbering of the C atoms in the bicyclic system, and the stereochemistry and the chirality (see Figure 2).

Discussion

Conclusion