Synthesis and Characterization of 5-MeO-DMT Succinate for Clinical Use
Alexander M. Sherwood, Romain Claveau, Rafael Lancelotta, Kristi W. Kaylo, Kelsey Lenoch
ACS Omega December 2, 2020 DOI: 10.1021/acsomega.0c05099 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Process development report Peer reviewed |
|---|---|
| Topics | 5-MeO-DMT DMT |
| Keywords | Yield engineering High-performance liquid chromatography Salt chemistry Active ingredient Impurity Process development Natural product Combinatorial chemistry Organic chemistry Pharmacology Process engineering Alkaloids |
| Citations | 38 |
| Key points | A multigram-scale synthesis of 5-MeO-DMT succinate was achieved with 99.86% purity and 49% net yield, suitable for clinical use. |
Abstract
To support clinical use, a multigram-scale process has been developed to provide 5-MeO-DMT, a psychedelic natural product found in the parotid gland secretions of the toad, Incilius alvarius. Several synthetic routes were initially explored, and the selected process featured an optimized Fischer indole reaction to 5-MeO-DMT freebase in high-yield, from which the 1:1 succinate salt was produced to provide 136 g of crystalline active pharmaceutical ingredient (API) with 99.86% peak area by high-performance liquid chromatography (HPLC) and a net yield of 49%. The report provides in-process monitoring, validated analytical methods, impurity formation and removal, and solid-state characterization of the API essential for subsequent clinical development.