Iyer, R. N., Favela, D., Zhang, G. & Olson, D. E. The iboga enigma: the chemistry and neuropharmacology of iboga alkaloids and related analogs. Nat. Prod. Rep. 38, 307–329 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kock, P., Froelich, K., Walter, M., Lang, U. & Dursteler, K. M. A systematic literature review of clinical trials and therapeutic applications of ibogaine. J. Subst. Abuse Treat. 138, 108717 (2022).

Article  CAS  PubMed  Google Scholar 

Wasko, M. J., Witt-Enderby, P. A. & Surratt, C. K. DARK classics in chemical neuroscience: ibogaine. ACS Chem. Neurosci. 9, 2475–2483 (2018).

Article  CAS  PubMed  Google Scholar 

Belgers, M. et al. Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Transl. Psychiatry 6, e826 (2016).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Koenig, X., Kovar, M., Boehm, S., Sandtner, W. & Hilber, K. Anti-addiction drug ibogaine inhibits hERG channels: a cardiac arrhythmia risk. Addict. Biol. 19, 237–239 (2014).

Article  CAS  PubMed  Google Scholar 

Thurner, P. et al. Mechanism of hERG channel block by the psychoactive indole alkaloid ibogaine. J. Pharmacol. Exp. Ther. 348, 346–358 (2014).

Article  PubMed  Google Scholar 

Alper, K. R., Stajić, M. & Gill, J. R. Fatalities temporally associated with the ingestion of ibogaine. J. Forensic Sci. 57, 398–412 (2012).

Article  CAS  PubMed  Google Scholar 

Koenig, X. & Hilber, K. The anti-addiction drug ibogaine and the heart: a delicate relation. Molecules 20, 2208–2228 (2015).

Article  PubMed  PubMed Central  Google Scholar 

Cameron, L. P. et al. A non-hallucinogenic psychedelic analogue with therapeutic potential. Nature 589, 474–479 (2021).

Article  CAS  PubMed  Google Scholar 

Glick, S. D., Kuehne, M. E., Maisonneuve, I. M., Bandarage, U. K. & Molinari, H. H. 18-Methoxycoronaridine, a non-toxic iboga alkaloid congener: effects on morphine and cocaine self-administration and on mesolimbic dopamine release in rats. Brain Res. 719, 29–35 (1996).

Article  CAS  PubMed  Google Scholar 

Rocha, J. M., Reis, J. A. S., Buoso, J. C., Hallak, J. E. C. & Dos Santos, R. G. Identifying setting factors associated with improved ibogaine safety: a systematic review of clinical studies. Eur. Arch. Psychiatry Clin. Neurosci. 273, 1527–1542 (2023).

Article  PubMed  Google Scholar 

Cherian, K. N. et al. Magnesium-ibogaine therapy in veterans with traumatic brain injuries. Nat. Med. 30, 373–381 (2024).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Noeller, G. E., Frampton, C. M. & Yazar-Klosinski, B. Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. Am. J. Drug Alcohol Abuse 44, 37–46 (2018).

Article  Google Scholar 

Davis, A. K., Barsuglia, J. P., Windham-Herman, A., Lynch, M. & Polanco, M. Subjective effectiveness of ibogaine treatment for problematic opioid consumption: short- and long-term outcomes and current psychological functioning. J. Psychedelic Stud. 1, 65–73 (2017).

Article  PubMed  PubMed Central  Google Scholar 

Dickel, D. F., Holden, C. L., Maxfield, R. C., Paszek, L. & Taylor, W. The alkaloids of Tabernanthe iboga. Part III. Isolation studies. J. Am. Chem. Soc. 80, 123–125 (1958).

Article  CAS  Google Scholar 

Jenks, C. W. Extraction studies of Tabernanthe iboga and Voacanga africana. Nat. Prod. Lett. 16, 71–76 (2002).

Article  CAS  PubMed  Google Scholar 

Gonzalez, B. et al. Efficient access to the iboga skeleton: optimized procedure to obtain voacangine from Voacanga africana root bark. ACS Omega 6, 16755–16762 (2021).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farrow, S. C. et al. Biosynthesis of an anti-addiction agent from the iboga plant. J. Am. Chem. Soc. 141, 12979–12983 (2019).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farrow, S. C. et al. Cytochrome P450 and O-methyltransferase catalyze the final steps in the biosynthesis of the anti-addictive alkaloid ibogaine from Tabernanthe iboga. J. Biol. Chem. 293, 13821–13833 (2018).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Trost, B. M., Godleski, S. A. & Genet, J. P. A total synthesis of racemic and optically active ibogamine. Utilization and mechanism of a new silver ion assisted palladium catalyzed cyclization. J. Am. Chem. Soc. 100, 3930–3931 (1978).

Article  CAS  Google Scholar 

Imanishi, T., Yagi, N. & Hanaoka, M. 1,6-Dihydro-3(2H)-pyridinones. X. 2-Azabicyclo[2.2.2]octane ring formation via intramolecular Michael reaction: total synthesis of (±)-ibogamine and (±)-epiibogamine. Chem. Pharm. Bull. 33, 4202–4211 (1985).

Article  CAS  Google Scholar 

Höck, S. & Borschberg, H. J. Enantioselective synthesis of (−)-(19R)-ibogamin-19-ol. Helv. Chim. Acta 89, 542–557 (2006).

Article  Google Scholar 

Harada, M. et al. Asymmetric total synthesis of an iboga-type indole alkaloid, voacangalactone, newly isolated from Voacanga africana. Org. Lett. 14, 5800–5803 (2012).

Article  CAS  PubMed  Google Scholar 

Mizoguchi, H., Oikawa, H. & Oguri, H. Biogenetically inspired synthesis and skeletal diversification of indole alkaloids. Nat. Chem. 6, 57–64 (2013).

Article  PubMed  Google Scholar 

Kruegel, A. C., Rakshit, S., Li, X. & Sames, D. Constructing iboga alkaloids via C–H bond functionalization: examination of the direct and catalytic union of heteroarenes and isoquinuclidine Alkenes. J. Org. Chem. 80, 2062–2071 (2015).

Article  CAS  PubMed  Google Scholar 

Zhang, G. et al. Synthesis of tertiary amines through extrusive alkylation of carbamates. Org. Lett. 24, 6208–6212 (2022).

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hughes, A. J. & Townsend, S. D. Gram-scale total synthesis of (±)-ibogamine. Org. Lett. 25, 4567–4570 (2023).

Article  CAS  PubMed  Google Scholar 

Hughes, A. J. & Townsend, S. D. Total synthesis of tabernanthine and ibogaline: rapid access to nosyl tryptamines. Eur. J. Org. Chem. 27, e202400442 (2024).

Article  CAS  Google Scholar 

Raucher, S. & Bray, B. L. Total synthesis of (±)-catharanthine. J. Org. Chem. 50, 3236–3237 (1985).

Article  CAS  Google Scholar 

Herdeis, C. & Hartke-Karger, C. Short and stereoselective synthesis of (±)-ibogamine via a vinylsulfone intermediate, IV. Liebigs Ann. Chem. 2, 99–104 (1991).

Article  Google Scholar 

Büchi, G., Coffen, D. L., Kocsis, K., Sonnet, P. E. & Ziegler, F. E. The total synthesis of iboga alkaloids. J. Am. Chem. Soc. 88, 3099–3109 (1966).

Article  Google Scholar 

Jana, G. K. & Sinha, S. Total synthesis of ibogaine, epiibogaine and their analogues. Tetrahedron 68, 7155–7165 (2012).

Article  CAS  Google Scholar 

Zhao, G. et al. Bioinspired collective syntheses of iboga-type indole alkaloids. Org. Lett. 18, 2447–2450 (2016).

Article  CAS  PubMed  Google Scholar