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

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