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

Robert B. Kargbo, Alexander M. Sherwood, Poncho Meisenheimer, Gary Tarpley

Synthesis January 8, 2020 DOI: 10.1055/s-0039-1691565 (opens in new tab)

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AI-extracted from the abstract
Characteristics Chemical synthesis protocol Peer reviewed
Topics Psilocybin
Keywords Yield engineering Combinatorial chemistry Hallucinogen Pharmacology Alkaloids
Citations 31
Key points An improved synthesis of psilocybin achieves 23% overall yield in five steps from an inexpensive acetoxyindole starting material without chromatography or aqueous workup.

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.

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