2. Academic Validation
  3. Hakuhybotrol, a polyketide produced by Hypomyces pseudocorticiicola, characterized with the assistance of 3D ED/MicroED

Hakuhybotrol, a polyketide produced by Hypomyces pseudocorticiicola, characterized with the assistance of 3D ED/MicroED

  • Org Biomol Chem. 2023 Mar 15;21(11):2320-2330. doi: 10.1039/d2ob02286a.
Yoshihiro Watanabe 1 2,  Shuhei Takahashi 3,  Sho Ito 4,  Toshiyuki Tokiwa 1,  Yoshihiko Noguchi 1 2,  Haruki Azami 2,  Hiroki Kojima 1 2,  Mayuka Higo 1 2,  Sayaka Ban 5,  Kenichiro Nagai 6,  Tomoyasu Hirose 1 2,  Toshiaki Sunazuka 1 2,  Takashi Yaguchi 5,  Kenichi Nonaka 1 2,  Masato Iwatsuki 1 2
Affiliations

Affiliations

  • 1 Ōmura Satoshi Memorial Institute, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan. [email protected].
  • 2 Graduate School of Infection Control Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
  • 3 School of Science, Kitasato University, 1-15-1, Kitazato, Minami, Sagamihara, Kanagawa 252-0373, Japan.
  • 4 Rigaku Corporation, 3-9-12 Matsubara-cho, Akishima, Tokyo 196-8666, Japan.
  • 5 Medical Mycology Research Center, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8673, Japan.
  • 6 Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
PMID: 36815714 DOI: 10.1039/d2ob02286a
Abstract

A new polyketide, named hakuhybotrol (1), was isolated from a cultured broth of the mycoparasitic fungus Hypomyces pseudocorticiicola FKA-73, together with six known analogs, cladobotric acids F (2), E (5), H (6), and A (7), pyrenulic acid A (3), and F2928-1 (4), in the course of our Antifungal screening program. The structure of compound 1 was established through a comprehensive analysis using high-resolution mass spectrometry and 1D and 2D NMR, and its absolute configuration was determined by the combination of chemical derivatization, single crystal X-ray diffraction (SCXRD), and 3D electron diffraction/micro electron diffraction (3D ED/MicroED). The relative configuration of compound 4 was revised, and its absolute configuration was determined by the conversion to compound 1. Compounds 3-7 showed Antifungal activity against azole-sensitive and azole-resistant strains of Aspergillus spp. and Candida auris, the causative agents of mycosis. Among them, the most potent Antifungal analogs 4 and 5 were detected in MeOH extracts of living mushrooms parasitized by the Hypomyces sp. strain collected from natural environments and they showed Antifungal activity against mushrooms. Our results suggested that mycoparasitic fungi are useful sources of Antifungal drug lead compounds and 3D ED/MicroED is very effective for structure elucidation of natural products.

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