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

Abstract

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-Obenzylpyrophosphate. 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.

Occurrence and use of hallucinogenic mushrooms containing psilocybin alkaloids

“…The compounds were originally synthesized by chemists at the Sandoz laboratories in Switzerland (Hofmann et al, 1958;Troxler et al, 1959). Several investigators have subsequently reported on the chemical synthesis of psilocybin (Ono et al, 1973;Repke et al, 1981;Ametamey et al, 1998;Yamada et al, 1998;Nichols and Frescas, 1999;Sakagami and Ogasawara, 1999;Yamada, 2000;, but only a few on the synthesis of psilocin (Nichols and Frescas, 1999;.…”

SAR of psilocybin analogs: Discovery of a selective 5-HT2C agonist

“…Known N-methylated derivatives 3 and 4 were synthesized following published procedures. 5,9,10 Treatment of 4-benzyloxyindole with oxalyl chloride and then with dimethylamine gave the 3-substituted oxamide. Amide reduction (LAH), N-methylation (NaH, MeI), and hydrogenation (H 2 , Pd(OH) 2 ) afforded N-methylpsilocin, 3.…”

“…The compounds prepared (3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) 8 are shown in Figure 2. Known N-methylated derivatives 3 and 4 were synthesized following published procedures.…”

Development of a psilocin immunoassay for serum and blood samples

“…The solution of 4-benzyloxy-N,N-dimethyltryptamine [15,16] substance 1 (2.6 mg, 0.009 mmol) in dry DMF (300 µl) was added and the mixture stirred for further 20 min at 0°C. Subsequently a solution of [ 3 H]methyl iodide (85 mCi, 1.176×10 −3 mmol, American Radiolabelled Chemicals, St. Louis, USA) in toluene (150 µl) was added and the resulting mixture was stirred overnight.…”