Improvements to the synthesis of psilocybin and a facile method for preparing the O-acetyl prodrug of psilocin

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 group s were removed by catalytic hydrogenation over palladium on carbon to affor d N,N-dimethyl-4-phosphoryloxytryptamine (psilocybin, 1). In view of diffic ulties 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-b enzyloxy-N,N-dimethyltryptamine in the presence of acetic anhydride and sod ium acetate.