Table 2.
Total syntheses of iboga alkaloids. The order in which the indole (I), isoquinuclidine (Q), and tetrahydroazepine (A) rings were formed is indicated. A “ / ” indicates that two ring systems were formed in the same step. NR = not reported (i.e., not enough information was provided to calculate an overall yield or determine step count).
| Year | Group | Alkaloid(s) | Formation Sequence | Step Count | Overall Yield (%) |
|---|---|---|---|---|---|
| 1965 | Buchi | (±)-Ibogamine (81) | Q → I → A | 14 | 1.3 |
| 1966 | Buchi | (±)-Ibogaine (1) | Q → I → A | 15 | 0.2 |
| 1967 | Sallay | (±)-Ibogamine (81) | A → Q → I | 14 | NR |
| 1968 | Nagata | (±)-Ibogamine (81) | Q → I → A | 16 | 0.8 |
| 1978 | Trost | (+)-Ibogamine (81) | I → Q → A | NR* | NR* |
| 1981 | Hanaoka | (±)-Ibogamine (81) | Q → I → A | 17 | 3.9 |
| 1985 | Kuehne | (±)-Ibogamine (81) | I/Q → A | 10 | 2.6 |
| 1985 | Raucher | (±)-Catharanthine (7) | Q → I → A | 11 | 9.0 |
| 1991 | Herdeis | (±)-Ibogamine (81) | Q → I → A | 8 | 14 |
| 1996 | Grieco | (±)-Ibogamine (81) | I → Q → A | 9 | 7.0 |
| 1999 | Fukuyama | (±)-Catharanthine (7) | Q → I → A | 17 | 6.0 |
| 2000 | White | (−)-Ibogamine (81) | A → Q → I | 15 | 4.6 |
| 2001 | Kuehne | (−)-Coronaridine (4) | I → Q/A | 10 | NR |
| 2005 | Hodgson | (+)-Ibogamine (81) | Q → I → A | 11 | 2.0 |
| 2006 | Borschberg | (−)-19-hydroxyibogamine | Q → I → A | 20 | 1.9 |
| 2012 | Sinha | (±)-Ibogaine (1) (±)-Ibogamine (81) |
Q → I → A | 9 9 |
9.4 5.6 |
| 2012 | Takayama | (−)-Voacangalactone (169) | Q → I → A | 25 | 3.2 |
| 2014 | Oguri | (−)-Catharanthine (7) | I → Q/A | 10 | 2.8 |
| 2015 | Sames | (±)-Ibogamine (81) | Q → I → A | 9 | 7.3 |
| 2016 | Luo | (+)-Ibogamine (81) | I → Q/A | 12 | 4.2 |
| 2016 | She | (±)-Ibogaine (1) (±)-Ibogamine (81) (±)-Tabertinggine (25) (±)-37 (±)-51 (±)-Iboluteine (177) (±)-Ervaoffines D (49) |
I → Q/A | 12 12 10 13 13 14 14 |
4.6 6.0 41 3.2 4.3 3.9 2.9 |
*
Trost synthesized (+)-ibogamine from an intermediate in 4 steps (17% yield). However, the synthesis of this intermediate from simpler precursors was not detailed, and thus, we cannot provide an overall step count and yield for the Trost synthesis.