Uncovering Hericenones from the Fruiting Bodies of <i>Hericium\nerinaceus</i> through Interdisciplinary Collaboration

<i>Hericium erinaceus</i> is an edible and medicinal\nmushroom. Previously, we found hericenones C–H from the fruiting\nbodies and erinacines A–I from the mycelia of the fungus. These\ncompounds stimulated nerve growth factor (NGF) synthesis both <i>in vitro</i> and <i>in vivo</i>; some have been suggested\nto be effective in the prevention and treatment of dementia. Recently,\nthe total synthesis of hericenones C–H and their derivatives\n(<b>1</b>–<b>4</b>) was reported by one of the\nauthors. We considered that the chemical synthetic route would also\nbe reasonable as a biosynthetic pathway of the compounds. Based on\nthe hypothesis, we investigated the endogenous existence of synthetic\nintermediates and products of the chemical synthesis in the fruiting\nbodies. The <i>n</i>-hexane-soluble part of the fruiting\nbodies of <i>H. erinaceus</i> was fractionated, and all\nthe fractions were subjected to a product ion scan and multiple reaction\nmonitoring (MRM) analysis by LC-MS/MS and compared to the authentic\nsynthesized compounds. The analysis indicated the endogenous existence\nof <b>1</b>–<b>4</b> and the dehydrated form of <b>2</b> or <b>3</b>. The dehydrated form was elucidated to\nbe (<i>Z</i>)-<b>5</b> by chemical synthesis, and\na plausible biosynthetic pathway was proposed.