Journal of Natural Products
February 20, 2020
Alexander M. Sherwood, Adam L. Halberstadt, Adam K. Klein et al.
79 citations
A new synthetic method allows access to tryptamine natural products found in psilocybin-producing mushrooms. Laboratory and animal experiments tested whether these compounds are psychoactive. In mice, the natural product baeocystin did not produce a head twitch response, a behavioral marker of psychedelic activity, even though its predicted breakdown product, norpsilocin, strongly activates the 5-HT2A receptor, which is associated with psychedelic effects. This suggests that baeocystin itself may not be psychedelic, despite its metabolite's activity.
ACS Omega
July 1, 2020
Jessica Sable, Tura Patterson, Gary Tarpley et al.
41 citations
A new chemical process produces over one kilogram of high-purity psilocybin, the active compound in psychedelic mushrooms, using a second-generation synthesis designed for large-scale manufacturing. The method improves on earlier procedures by optimizing the Speeter-Anthony tryptamine synthesis to create the intermediate psilocin with better control and impurity removal. It then directly phosphorylates psilocin with phosphorous oxychloride, avoiding a complex benzyl-protecting group strategy used in previous methods. This approach addresses challenges in yield, purity, atom economy, and suitability for pilot plant-scale reactors, providing a more efficient and consistent route for producing psilocybin under current Good Manufacturing Practices.
Synthesis
January 8, 2020
Robert B. Kargbo, Alexander M. Sherwood, Poncho Meisenheimer et al.
31 citations
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.
Acta Crystallographica Section C Structural Chemistry
December 20, 2021
Alexander M. Sherwood, Robert B. Kargbo, Kristi W. Kaylo et al.
10 citations
Psilocybin, a natural product from psychoactive fungi, exists in three distinct crystal forms: Hydrate A, Polymorph A, and Polymorph B. This article presents newly solved crystal structures for the two anhydrate forms using X-ray diffraction and computational methods. Analysis of psilocybin samples produced between 1963 and 2021 shows that all contain one or more of these three forms, with no additional forms needed to explain their diffraction patterns. The composition correlates with process methods, sample age, and storage conditions. The authors also identify that a recently granted patent incorrectly described a mixture of about 81% Polymorph A and 19% Polymorph B as a single-phase variant, recommending revision of such characterizations.
ACS Omega
February 7, 2022
Robert B. Kargbo, Alexander M. Sherwood, Poncho Meisenheimer et al.
5 citations
A thermodynamically controlled crystallization process for psilocybin, a serotonergic agonist granted breakthrough therapy status for depression, produces crystals with stronger interactions, a controlled particle size distribution, and an improved impurity profile compared to a faster, kinetically controlled process that yields smaller particles. Real-time monitoring with high-resolution inline microscopy measured particle size and metastable zone width and nucleation induction. Water recrystallization forms polymorph B (trihydrate) independently of the method, while polymorph A (anhydrate) and polymorph H (anhydrate) depend on drying: room-temperature vacuum drying yields mainly polymorph A, and heating even at low temperatures produces a mixture of polymorphs A and H.