Abstract Advanced clinical trials investigate the Psilocybe magic mushroom natural product psilocybin as a treatment against major depressive disorder. Currently, synthetic material is used to meet the demand for legitimate pharmaceutical purposes. Here, we report an in vitro approach to biocatalytically produce psilocybin on a solid‐phase matrix charged with five covalently bound biosynthetic...
The formal synthesis of (±)-salvinorin A is presented. Our approach utilizes two distinct gold(I) catalytic processes. The combination of a gold(I)-catalyzed reaction with an intermolecular Diels-Alder reaction followed by a gold(I)-catalyzed photoredox reaction generated in eight steps the framework of the natural product with high diastereoselectivity.
Abstract Psilocin ( 1 ) is the dephosphorylated and psychotropic metabolite of the mushroom natural product psilocybin. Oxidation of the phenolic hydroxy group at the C‐4 position of 1 results in formation of oligomeric indoloquinoid chromophores responsible for the iconic blueing of bruised psilocybin‐producing mushrooms. Based on previous NMR experiments, the hypothesis included that the...
A concise enantioselective total synthesis of the neoclerodane diterpene (-)-salvinorin A is reported. The stereogenic center at C-12 was installed by catalytic asymmetric propargylation with excellent enantioselectivity, and the remaining six stereogenic centers were set up highly diastereoselectively under substrate control. As for our previous synthesis of racemic salvinorin A, two...
We report investigations of the use of cucurbit[8]uril (CB[8]) macrocycles as an antidote to counteract the in vivo biological effects of phencyclidine. We investigate the binding of CB[8] and its derivative Me4 CB[8] toward ten drugs of abuse (3-9, 12-14) by a combination of 1 H NMR spectroscopy and isothermal titration calorimetry in phosphate buffered water. We find that the cavity of CB[8]...
Abstract Psilocybin, the principal indole alkaloid of Psilocybe mushrooms, is currently undergoing clinical trials as a medication against treatment‐resistant depression and major depressive disorder. The psilocybin supply for pharmaceutical purposes is met by synthetic chemistry. We replaced the problematic phosphorylation step during synthesis with the mushroom kinase PsiK. This enzyme was...
Abstract The psychotropic effects of Psilocybe “magic” mushrooms are caused by the l ‐tryptophan‐derived alkaloid psilocybin. Despite their significance, the secondary metabolome of these fungi is poorly understood in general. Our analysis of four Psilocybe species identified harmane, harmine, and a range of other l ‐tryptophan‐derived β‐carbolines as their natural products, which was confirmed...
Abstract The fungal genus Psilocybe and other genera comprise numerous mushroom species that biosynthesize psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine). It represents the prodrug to its dephosphorylated psychotropic analogue, psilocin. The colloquial term “magic mushrooms” for these fungi alludes to their hallucinogenic effects and to their use as recreational drugs. However,...
Abstract Psilocybin (4‐phosphoryloxy‐ N , N ‐dimethyltryptamine) is the main alkaloid of the fungal genus Psilocybe , the so‐called “magic mushrooms.” The pharmaceutical interest in this psychotropic natural product as a future medication to treat depression and anxiety is strongly re‐emerging. Here, we present an enhanced enzymatic route of psilocybin production by adding TrpB, the tryptophan...
Salvinorin A (1) is natural hallucinogen that binds the human κ-opioid receptor. A total synthesis has been developed that parlays the stereochemistry of l-(+)-tartaric acid into that of (-)-1 via an unprecedented allylic dithiane intramolecular Diels-Alder reaction to obtain the trans-decalin scaffold. Tsuji allylation set the C9 quaternary center and a late-stage stereoselective chiral...