“Fruiting Liquid” of Mushroom-Forming Fungi, A Novel Source of Bioactive Compounds – Fruiting-Body Inducer and HIF and Axl Inhibitors

[Image: see text] In general, mushroom-forming fungi secrete liquid on the surface of mycelia just before fruiting-body formation. However, no researchers in mushroom science have paid attention to the liquid until now. We formulated a hypothesis that the liquid plays an important role(s) in the formation of the fruiting body and produces various bioactive compounds and named it the “fruiting liquid (FL)”. Four novel compounds (1–4) were isolated from FL of Hypholoma lateritium and Hericium erinaceus. The structures of 1–4 except for their stereochemistry were determined by interpretation of MS and NMR data. The absolute configurations of compounds 1–4 were determined by quantum chemical calculation of the ECD spectrum, by single-crystal X-ray diffraction analyses, or by chemical syntheses. Compounds 1, 3, and 4 induced fruiting body formation of Flammulina velutipes. Compound 4 inhibited the activity of hypoxia-inducible factor, and compounds 2–4 suppressed receptor tyrosine kinase (Axl) expression.