Zur Chemie des Psilocins und verwandter Tryptaminverbindungen im pharmakologischen und ökologischen Kontext

Dephosphorylation of psilocybin, the main alkaloid of Psilocybe (so-called magic) mushrooms, yields its bioactive congener psilocin (N,N-dimethyl-4-hydroxytryptamine). On top, psilocin is the chromogenic subtrate of the injury-triggered bluing reaction of these mushrooms. This work adresses the biochemical characterization and structural product elucidation of this very reaction. Initially upon wounding, the phosphatase PsiP catalyzes the conversion of psilocybin to psilocin, which is then oxidized to a heterogenous mixture of oligo- or polymers by the laccase PsiL. The coupling involves mainly the positions C-5 and C-7. The primary blue chromophore was identified as the psilocin-derived quinoid 7,7-didehydrodimer. The bluing reaction and its products, to a degree resembling eumelanins and tannins, are discussed as a potential defense strategy (respectively an evolutionary advantage) of Psilocybe. A long-postulated intramolecular hydrogen bond in psilocin is experimentally verified. This bond plausibly provides the basis for both its oxidation lability as well as outstanding psychoactive properties, as opposed to e.g. its 5-hydroxy isomer bufotenin. Furthermore, this work identifies the secondary amine analogon of psilocin (norpsilocin) as a Psilocybe natural product, and contributes to the characterization of the native alkaloid profile of these mushrooms. Lastly, issues of large scale production of the psychotropic tryptamines are covered, which are of high relevance regarding the encouraging results of clinical trials on psilocybin as a future therapeutic for e.g. depressive disorders.