The Total Synthesis of (±)-Ibogamine and of (±)-Epiibogamine

Biosynthetically Inspired Transformation of Iboga to Monomeric Post-iboga Alkaloids

“…Synthetic interests toward the post-iboga alkaloids have been mostly focused on heterodimeric vinblastine (8) and vincristine (9) 18 and the synthetic access to monomeric post-iboga alkaloids has remained relatively underdeveloped. Few prominent examples include the synthesis of (G)-tabertinggine (11) by the Bü chi group en route to their first total synthesis of (G)-ibogamine (2) 19,20 and the conversion of natural ibogaine (1) to iboluteine (16) by Bartlett and coworkers. 2 More recently, She and coworkers reported a scalable total synthesis of (G)-tabertinggine (11) and showed an oxidative conversion of (G)-ibogaine (1) to (G)-ervaoffine D (17).…”

Progress in the Synthesis of Iboga-alkaloids and their Congeners

“…40,41 The tosylhydrazone of the endo compound was separated out as a crystalline solid from a mixture of endo/exo products. The endo-isomer was wrongly assigned to exo-isomer by Krow and co-workers and the configuration of the ethyl group was confirmed by Hodgson's group based on the single-crystal X-ray structure.…”

“…Since Büchi's total synthesis of ibogamine, 40 the majority of the syntheses reported have adopted the strategy of generating β-(indolylacetyl or indolylethyl)isoquinuclidines or indolyl-isoquinuclidines followed by electrophilic cyclization leading to the formation of hydroazepine ring. An alternative approach involves the generation of isoquinuclidine fused seven-membered ketone, a key precursor followed by cyclization to the iboga-scaffold by the Fischer indolization method.…”

“…40 Several other syntheses were then followed. In each of these syntheses, the formation of a 2-azabicyclo[2.2.2]octane (or isoquinuclidine) ring bearing a two-carbon chain at the requisite position of the ring was the crucial step.…”

Enantioselective Pictet–Spengler Condensation to Access the Total Synthesis of (+)‐Tabertinggine

“…The challenging architectures of iboga type alkaloids combined with their intriguing biological activities have stimulated extensive synthetic efforts towards their chemical total synthesis [7,8] . G. Büchi employed an intermolecular Diels‐Alder reaction to construct the azabicyclo[2.2.2]octane skeleton followed by a cyclization to accomplish the total synthesis of (±)‐ibogamine in 1965 for the first time [8a] . Ever since then, many other syntheses of the iboga‐type alkaloid have been reported [8,9] .…”