[Osaka Institute of Technology] Elucidating Molecules Involved in Mushroom Efficacy

A research group led by Associate Professor Shoji Kobayashi of the Department of Applied Chemistry at Osaka Institute of Technology (President: Shin Inoue) has discovered a simple method to produce various oxysterols related to mushroom growth and efficacy, and has clarified the precise stereochemical structures of sterols that were previously unclear. Sterols are molecules produced in the bodies of animals, plants, and fungi, and are thought to be deeply involved in the efficacy of foods. The results of this research are expected to lead to the elucidation of the stereochemical structures of highly oxidized sterols and the biosynthetic pathways of sterols in vivo, which will be useful for the development of pharmaceuticals and other products.

Key Points of This Research:

* Simple and comprehensive synthesis of various sterols using chemical species that can exist in vivo * Development of a method to directly introduce an oxygen functional group into the CD ring of the steroid skeleton, which is rarely achieved. * Clarification of the stereochemical structure of quaternary carbon centers in the steroid skeleton, which were difficult to analyze with conventional methods.

Outline Diagram of This Research

Sterols are one of the main components produced in the bodies of animals, plants, and fungi. In animals such as humans, they are thought to be produced mainly from cholesterol, and in fungi, mainly from ergosterol. In mushrooms, which are fungi, sterol components are thought to be deeply involved in taste and efficacy. The diversity of structures of sterols produced by fungi is thought to be due to the oxidation of various parts of the steroid skeleton through oxidative metabolism within the fungal cells, accompanied by various functional group transformations and cleavage/formation of bonds.

Based on a self-devised hypothesis for sterol biosynthesis, this research group discovered a method to directly oxidize the CD ring of the steroid skeleton, which has low reactivity, using reaction conditions similar to the biological environment. In particular, they found that in oxygen oxidation involving radicals, only the 14-position of the steroid skeleton is selectively oxidized, and discovered that the direction of oxygen introduction (stereochemistry) is also completely controlled.

Generally, sterols have a large number of carbon atoms and complex skeletal structures. Therefore, it is not easy for scientists who discover sterols from parent organisms to accurately determine their chemical structures, including their stereochemistry, and there are many cases of erroneous reports. In this study, we supplied various molecules with oxidized CD rings through reliable synthetic methods and reliably determined the chemical structures of all of them using two-dimensional nuclear magnetic resonance and single-crystal X-ray structure analysis. In particular, the complete determination of the stereochemistry of the controversial quaternary carbon centers (positions 8, 9, and 14) and the disclosure of their spectroscopic data are expected to be useful for the structural determination of unknown sterols in the future.

Single-crystal X-ray structure analysis of synthesized compounds

Furthermore, the research group synthesized rare oxysterols found in the edible mushrooms shiitake and annin-kou from molecules with oxidized CD rings, and clarified their stereochemical structures for the first time. Gargalol C, one of the synthesized molecules, has been found to have activity to inhibit osteoclast formation, and the results of this study are expected to be useful for the future development of osteoporosis drugs.

This research group's chemical synthesis is carried out using chemical species that can exist in vivo, such as oxygen and iron ions, and in accordance with the inherent reactivity of the molecules. Therefore, the results of this research also contribute to the elucidation of the in vivo production process (biosynthetic pathway) of sterols that have not yet been demonstrated.

The results of this research were published in Chemistry Europe, the flagship journal of the European Chemical Society. (Open Access, Published June 18, 2026).

This research was supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (JSPS KAKENHI) Grant Number "24K08737".

Glossary:

*Steroid Skeleton

The basic skeleton common to sterols. It is a tetracyclic skeleton formed by the fusion of three 6-membered rings and one 5-membered ring. They are named rings A, B, C, and D from the bottom left.

Paper Information

Paper Title: Bioinspired Aerobic Oxidation to Functionalize the CD Ring of the Steroid Framework: Synthesis and Stereochemical Assignments of Gargalol C and Related Oxysterols

Authors: Hinata Togo, Yui Kanda, Shoji Kobayashi* (*Lead Author)

Journal: ChemistryEurope, 2026; 4: e70325. (Open Access)

DOI: 10.1002/ceur.70325

URL: https://doi.org/10.1002/ceur.70325

Publication Date: June 18, 2026 (Online Publication)