An approach to the synthesis of ibogaine

✍ Scribed by Stephen I. Sallay

• Publisher: Elsevier Science
• Year: 1964
• Tongue: French
• Weight: 327 KB
• Volume: 5
• Category: Article
• ISSN: 0040-4039
• DOI: 10.1016/s0040-4039(00)70406-0

✦ Synopsis

IN view of the increasing interest in iboga alkaloids I should like to present some of the preliminary steps toward a total synthesis of ibogaine (I) (1). The successful, stereochemically controlled synthesis of the tetracyclic indole (XVIa) suggests a feasible pathway for the synthesis of I and some of its congeners. The cis-fused fl rings of XVIa were constructed from the cis-enedione (IIa) (2), which, after suitable modifications (11~1 --z IIIa -> Via), was subjected to the Beckmann rearrangement to give VIIIa. The lactam was then reduced to the cis-aminoketal (Xa). -The aminoketone derived from Xa underwent indole formation, producing the A-D ring system of XVIa and ibogaine (I). Parallel transformations of the stereochemically more stable transenedione (IIb) were carried out, the availability of the trans series (IIIb-VIIIb and Xb) being helpful in determining the configurations during every step of the synthesis. Gas chromatography proved that the separately equilibrated IIa and IIb isomers reached a cis//trans ratio of 1:5.7. In spite of the stereochemical instability of IIa (3,4), it proved to be a useful starting material. The isolated double bond of bo;h epimers (IIa,b) survived all the steps and was found to be particularly helpful in verifying the structures of VIa,b and VIIIa,b (vide infra).