Chemistry

“Psilocybin is the psychotropic tryptamine-derived natural product of psilocybe carpophores, the so-called ‘magic mushrooms’. although its structure has been known for 60 years, the enzymatic basis of its biosynthesis has remained obscure. we characterized four psilocybin biosynthesis enzymes, namely i) psid, which represents a new class of fungal l-tryptophan decarboxylases, ii) psik, which catalyzes the phosphotransfer step, iii) the methyltransferase psim, catalyzing iterative n-methyl transfer as the terminal biosynthetic step, and iv) psih, a monooxygenase. in a combined psid/psik/psim reaction, psilocybin was synthesized enzymatically in a step-economic route from 4-hydroxy-l-tryptophan. given the renewed pharmaceutical interest in psilocybin, our results may lay the foundation for its biotechnological production.”

“Psilocybin is found in a family of mushrooms commonly known as ‘magic mushrooms’ that have been used throughout history to induce hallucinations. in the late 1950s albert hofmann, of sandoz laboratories, identified and synthesized the psychoactive compounds psilocybin and psilocin which are found in psilocybe mushrooms. psilocybin was marketed by sandoz as indocybin for basic psychopharmacological and therapeutic clinical research. psilocybin saw a rapid rise in popularity during the 1960s and was classed as a schedule i drug in 1970. this led to a significant decrease in psilocybin research. recently, however, preliminary studies with psilocybin have shown promise as potential for the treatment of obsessive compulsive disorder, alcohol addiction, tobacco addiction, and major depressive disorder, and the treatment of depression in terminally ill cancer patients. this review describes in detail the synthesis, metabolism, pharmacology, adverse drug reactions, and importance of psilocybin to neuroscience in the past and present.”

“An improved procedure to accomplish the o-phosphorylation of 4-hydroxy- n,n-dimethyltryptamine (psilocin 5) is reported that utilizes reaction between the o-lithium salt of 5 and tetra-o-benzylpyrophosphate. the o- benzyl groups were removed by catalytic hydrogenation over palladium on carbon to afford n,n-dimethyl-4-phosphoryloxytryptamine (psilocybin, 1). in view of difficulties encountered in the preparation of 1, it is suggested that 4-acetoxy-n,n-dimethyltryptamine (2) may be a useful alternative for pharmacological studies. the latter was obtained following catalytic o- debenzylation of 4-benzyloxy-n,n-dimethyltryptamine in the presence of acetic anhydride and sodium acetate.”

“The concise large-scale syntheses of psilocin (1) and psilocybin (2), the principal hallucinogenic constituents of ‘magic mushroom’, were achieved without chromatographic purification. the key step in the synthesis of 2 was the isolation of the dibenzyl-protected intermediate (7) as a zwitterionic derivative (8), which was completely identified by means of 2d nmr analyses.”

“The structure of psilocybin, the psychotropic active principle of the mexican mushroom psilocybe mexicana heim, has been elucidated. psilocybin is the phosphoric acid ester of 4-hydroxy-dimethyltryptamine. this structure was confirmed by total synthesis.”

“Various modifications were made in the molecular structure of the natural psychotropic substances psilocybin {(i)} and psilocin (11) to obtain an insight into the relationship between structure and psychotropic action of this group of substances. a description is given of the synthesis and properties of the position isomers of i and {ii} with a phosphoryloxy or hydroxy group in position 5, 6 or 7, of the four isomeric hydroxygramines, and of a series of further derivatives of 4-hydroxy-indole in which the structure of {ii} was systematically modified, i.e. psilocin derivatives with other substitution at the ω-nitrogen; derivatives of {ii} substituted at the indole nitrogen; psilocin derivatives with one additional methylene group in the side-chain or with a methyl-substituted or hydroxylated side-chain; phosphoric acid esters of some derivatives of {ii;} esters of {ii} with organic carbonic and sulfonic acids, with methylcarbaminic and with sulfuric acid; position isomers of psilocin with the dimethylaminoethyl side-chain in position 1 or 2.”