Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin

An improved chemical procedure for synthesizing psilocybin, the psychoactive compound in magic mushrooms, is reported. The method uses the O-lithium salt of psilocin reacting with tetra-O-benzylpyrophosphate, followed by catalytic hydrogenation to remove benzyl groups. Because psilocybin preparation is difficult, the authors suggest 4-acetoxy-N,N-dimethyltryptamine as a useful alternative for pharmacological studies. This alternative is obtained by catalytic O-debenzylation of 4-benzyloxy-N,N-dimethyltryptamine in the presence of acetic anhydride and sodium acetate.

Study at a glance

Abstract

An improved procedure to accomplish the O-phosphor- ylation of 4-hydroxy-N,N-dimethyltryptamine (psilocin 5) is report- ed that utilizes reaction between the O-lithium salt of 5 and tetra-O- benzylpyrophosphate. The O-benzyl groups were removed by cata- lytic hydrogenation over palladium on carbon to afford N,N-dime- thyl-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 cat- alytic O-debenzylation of 4-benzyloxy-N,N-dimethyltryptamine in the presence of acetic anhydride and sodium acetate.