Scientists from University of Pittsburgh have synthesized novel psychedelic compounds. These compounds, belonging to the clavine alkaloid class of psychedelics, have undergone total synthesis for the first time allowing for synthesis of derivatives and structural activity relationship (SAR) studies.
Description
The novel psychedelics bind to important serotonin receptors. SAR studies will allow for the development and optimization of new clinically useful non-hallucinogenic psychedelic agents.
Applications
Psychiatric medicine
Advantages
There is growing interest in the use of psychedelics as therapeutic agents in psychiatry with ongoing clinical trials in conditions including depression, anxiety, and post-traumatic stress disorder (PTSD), with compounds like lysergic acid diethylamide (LSD) or psilocybin. Compounds with selective interaction with dopamine and serotonin receptors have shown the highest potential to be clinically effective. The identification of effective compounds with less side effects remains an unmet clinical need.
Using catalytic asymmetric cyclopropanation of allene, a regiospecific Pd-catalyzed enone formation, and two intramolecular Diels–Alder reactions for indole/indoline annulations, the first total synthesis of natural (+)-cycloclavine and other clavine alkaloids has been performed. The ability to stereoselectively synthesize derivatives of the clavine alkaloid scaffold will allow for SAR studies to identify compounds of highest clinical benefit with a lower risk profile, advancing the understanding of the mechanism of action for the therapeutic effects of this class of compounds.
Invention Readiness
Total asymmetric synthesis of clavine alkaloids has been achieved and in vitro studies show selective binding to serotonin receptors. Optimization of compound design through SAR studies will allow for more potent psychedelic discovery.
IP Status
https://patents.google.com/patent/WO2023018480A1
