A streamlined synthesis of 5-methoxy-N,N-dimethyltryptamine, bufotenin, and bufotenin prodrugs from melatonin
ChemRxiv November 26, 2025 Anton A. Homon, P. V. Vara Prasad, Elham Pourian et al.
A streamlined, chromatography-free synthesis of 5-MeO-DMT from melatonin achieves 76% overall yield, producing 64 g of analytically pure product in under 5 days. Demethylation of 5-MeO-DMT yields bufotenin hydrobromide in 51% yield (22 g) within an additional 2 days. Candidate prodrugs of bufotenin are prepared to potentially improve nanoformulation and blood-brain-barrier passive uptake. The method uses inexpensive, widely available melatonin, avoiding expensive starting materials, extensive chromatography, and late-stage chemistries that raise toxicity concerns.