A paper on sterol oxidation—which led to the synthesis and structural determination of mushroom-derived natural products—has been published in ChemistryEurope!

Our research findings regarding the synthesis of oxysterols derived from mushrooms have been published in ChemistryEurope, the flagship journal of Wiley!

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

Hinata Togo, Yui Kanda, Shoji Kobayashi*

The original paper is here. （Open Access）

Sterols are among the major components produced by fungi and are believed to play crucial roles in the taste and physiological properties of mushrooms.

In a 2025 paper, we reported straightforward syntheses of fungal sterols from a possible biosynthetic precursor, ergosterol, using reaction conditions that mimic biological environment. We furthermore discovered that some of the synthesized molecules inhibit the aggregation of β-amyloid, a causative factor involved in dementia.

The structural diversity of sterols produced by fungi is thought to stem from the oxidative metabolism of the steroid skeleton within the fungi.

Based on the original hypothesis of sterol biosynthesis, we investigated a method for the direct introduction of oxygen functional groups onto the CD rings of the steroid skeleton—an approach that had rarely been attempted previously. As a result, we successfully introduced hydroxyl groups directly at the C-8, C-9, C-11, C-14, and C-15 positions of the CD rings.

In particular, we demonstrated that under radical-mediated oxidation conditions, oxidation occurs selectively at the C-14 position, with the orientation (stereochemistry) of the oxygen introduction being completely controlled.

In general, accurately determining the chemical structures and stereochemistry of naturally occurring sterols is challenging due to their complex structures.

In this study, we synthesized various oxysterols featuring a hydroxyl group at the CD ring by reliable synthetic methods and determined their structures through two-dimensional nuclear magnetic resonance (NMR) spectroscopy and single-crystal X-ray structural analysis.

The full elucidation of the stereo-configuration at the quaternary carbon centers (positions 8, 9, and 14) would contribute significantly to the structural determination of unknown sterols in the future.

Furthermore, we synthesized natural products discovered from edible mushrooms such as "shiitake" and "anningkou" via intermediates fuctionalized at the CD ring, which resulted in the elucidation of configurations of unconviced natural products.

One of the synthesized molecules, "gargalol C," is known to inhibit osteoclast formation; therefore, the findings of this study could contribute to the future development of drugs for osteoporosis.

While our research primarily focuses on chemical synthesis, our overall approach is based on utilizing chemical species naturally present in living organisms—such as oxygen and iron ions—to effect chemical transformations that align with the intrinsic reactivity of the individual molecules.

Consequently, the findings of this research contribute to elucidating the sterol biosynthetic pathway, a process that had not previously been experimentally demonstrated.

The Supporting Information accompanying this paper spans 40 pages (134 pages including spectral data) and contains valuable information. Please look at as well.

The actual experiments were conducted by Hinata Togo, who completed her master's program this past March, and Yui Kanda, currently a second-year master's student.

To isolate products with similar structures, the two applied exceptional purification techniques and worked energetically on synthesis experiments day after day, ultimately succeeding in elucidating the molecular structures.

Dealing with unstable products prone to decomposition must have been challenging, and there were likely moments when they felt like giving up. Yet, they persevered and saw the project through to the end.

Both achieved outstanding results. Congratulations!

Yui still has some time left in her master's program, so let’s keep working hard together toward the next goal!

All of us in the laboratory remain committed to achieving outstanding research results that contribute to society.