An Improved, Practical, and Scalable Five-Step Synthesis of Psilocybin

2020/01/08 by Robert B. Kargbo, Alexander M. Sherwood, Poncho Meisenheimer +1 · 32 citations
Chemistry · Pharmacology, Toxicology and Pharmaceutics · Psychology · #Alkaloids: synthesis and pharmacology #Chemical synthesis and alkaloids #Chemistry #Combinatorial chemistry #Hallucinogen #Pharmacology #Psilocybin #Psychedelics and Drug Studies #Yield (engineering)

paper · pdf · doi:10.1055/s-0039-1691565

published in Synthesis 52(05), 688-694 (Thieme Medical Publishers (Germany))

openalex publication_date 2020/01/08 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/28

Abstract

Described herein is an improved synthesis of 3-[2-(dimethylamino)ethyl]-1H-indol-4-yl dihydrogen phosphate (psilocybin). The protocol outlines: synthesis of multigram quantities of psilocybin, identification of critical in-process parameters, and isolation of psilocybin without the use of chromatography, TLC, or aqueous workup. The synthesis furnishes psilocybin in five steps in 23% overall yield from an inexpensive acetoxyindole starting material. With specific focus on process control and impurity fate and removal, the improved procedure is amenable to providing high-quality psilocybin.

Citations

• Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin
• Pilot Study of Psilocybin Treatment for Anxiety in Patients With Advanced-Stage Cancer
• Psychiatry & the psychedelic drugs. Past, present & future

Cited by

• Psilocybin promotes neuroplasticity and induces rapid and sustained antidepressant-like effects in mice
• Direct Phosphorylation of Psilocin Enables Optimized cGMP Kilogram-Scale Manufacture of Psilocybin. [europepmc]
• A Review of Synthetic Access to Therapeutic Compounds Extracted from Psilocybe . [europepmc]
• Psychedelic-like Activity of Norpsilocin Analogues. [europepmc]
• Mild and Chemoselective Triethylsilane-Mediated Debenzylation for Phosphate Synthesis. [europepmc]
• Synthesis and In Vitro Profiling of Psilocin Derivatives: Improved Stability and Synthetic Properties. [europepmc]
• Efficient Acyloxymethylation of Psilocin and Other Tryptamines Yielding ACOM Prodrugs for Psychedelic-Assisted Therapy. [europepmc]
• Design, Synthesis, and Pharmacokinetic Profiling of Fluorinated Reversible N -Alkyl Carbamate Derivatives of Psilocin for Sub-Hallucinogenic Brain Exposure. [europepmc]

Related

• Improvements to the Synthesis of Psilocybin and a Facile Method for Preparing the O-Acetyl Prodrug of Psilocin
• De Novo Biosynthesis of Antidepressant Psilocybin in Escherichia coli
• Dissimilar Reactions and Enzymes for Psilocybin Biosynthesis in Inocybe and Psilocybe Mushrooms
• Synthesis and characterization of high‐purity N,N‐dimethyltryptamine hemifumarate for human clinical trials
• The Effect of Two Indicators of Culture Medium and Environmental Humidity in Increasing the Production Rate of Secondary Metabolite Psilocybin in Two Cultivars of The Medicinal Mushroom Strophoria Cubensis