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.
An improved chemical synthesis of psilocybin produces multigram quantities in five steps with 23% overall yield from an inexpensive acetoxyindole starting material. The protocol identifies critical in-process parameters and isolates psilocybin without chromatography, thin-layer chromatography, or aqueous workup. The procedure emphasizes process control and impurity fate and removal to deliver high-quality psilocybin.