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Photoreaction products of extract from the fruiting bodies of Polyozellus multiplex

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Abstract

Photochemical reactions are powerful tools for synthesizing organic molecules. The input of energy provided by light offers a means to produce strained and unique molecules that cannot be assembled using thermal protocols, allowing for the production of immense molecular complexity in a single chemical step. Furthermore, unlike thermal reactions, photochemical reactions do not require active reagents such as acids, bases, metals, or enzymes. Photochemical reactions play a central role in green chemistry. This article reports the isolation and structure determination of four new compounds (1–4) from the photoreaction products of the Polyozellus multiplex MeOH ext. The structures of the new compounds were elucidated using MS, IR, comprehensive NMR measurements and microED. The four compounds were formed by deacetylation of polyozellin, the main secondary metabolite of P. multiplex, and addition of singlet oxygen generated by sunlight. To develop drugs for treating Alzheimer’s disease (AD) on the basis of the amyloid cascade hypothesis, the compounds (1–4) obtained by photoreaction were evaluated for BACE1 inhibitory activity. The hydrolysates (5 and 6) of polyozellin, the main secondary metabolites of P. multiplex, were also evaluated. The photoreaction products (3 and 4) and hydrolysates (5 and 6) of polyozellin showed BACE1 inhibitory activity (IC50: 2.2, 16.4, 23.3, and 5.3 μM, respectively).

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Acknowledgements

The authors thank Dr. Hiroyasu Sato and Mr. Keigo Takahira (Rigaku Corporation, Tokyo, Japan) for their advice and support in this MicroED measurement.

Funding

This work was supported in part by a grant from the Dementia Drug Resource Development Center Project (DRC), the Ministry of Education, Culture, Sports, Science and Technology (MEXT), Japan (S1511016).

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Authors and Affiliations

  1. Department of Pharmacognosy and Phytochemistry, Meiji Pharmaceutical University, Noshio 2-522-1, Kiyose-Shi, Tokyo, 204-8588, Japan

    Hayato Otsuka, Emi Shimizu, Takamasa Yamaguchi, Hiroaki Sasaki, Kiyotaka Koyama & Kaoru Kinoshita

  2. Department of Chemistry, Chemical R&D Laboratory, SPERA PHARMA, Inc, 17-85, Jusohonmachi 2-Chome, Yodogawa-Ku, Osaka, 532-0024, Japan

    Keiyo Nakai & Mitsuhisa Yamano

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  1. Hayato Otsuka
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Correspondence to Kaoru Kinoshita.

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Otsuka, H., Nakai, K., Shimizu, E. et al. Photoreaction products of extract from the fruiting bodies of Polyozellus multiplex. J Nat Med (2024). https://doi.org/10.1007/s11418-024-01790-6

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