A new chemical method produces ibogaine in seven steps from pyridine, enabling gram-scale synthesis. This approach also creates three additional iboga alkaloids, the unnatural enantiomer (+)-ibogaine, and four analogues. Biological tests show that (+)-ibogaine does not affect cortical neuron growth like natural ibogaine, while (-)-10-fluoroibogamine strongly promotes neuron growth and potently modulates the serotonin transporter. The work provides a platform for making iboga alkaloids and related compounds for further study, supporting research into their therapeutic potential for addiction and other neuropsychiatric conditions.
Iboga alkaloids, a family of natural products including the anti-addictive compound ibogaine and the chemotherapeutic precursor catharanthine, have inspired chemists and biologists for over 120 years. This review covers advances from 2000 to 2020 in their biosynthesis and chemical synthesis, as well as their development as next-generation neurotherapeutics for mental illness. The authors provide historical context for recent discoveries and highlight unresolved questions. Although significant progress in chemistry and pharmacology has occurred since the 1960s, the iboga alkaloids continue to drive scientific innovation.