Some information about my Diploma Work, done in the lab of Prof. R. Neier, from January 2000 to September 2000.
The Iboga family contains now more than 60 alkaloids of similar
structure and more than 300 indole alkaloids have been discovered in
plants from the Tabernaemonthana gender, close to Tabernanthe
[5,6]. It was found in the 1960s that vinblastine and vincristine,
isolated from Catharanthus roseus, could be used in the treatment
of cancers. They are still in use today . They contain a closely
related to the Iboga type part.
Vinblastine (R = CH3) and vincristine
(R = CHO), two alkaloids with
Since the first total synthesis of (▒)-ibogamine, made by Büchi et al. in 1965 , around fifteen other synthesis have been published. And the group of Prof. Neier had already worked on the early steps of a new concise synthesis. The goal of my diploma work was (quite resumed !) to find out if the idea for a final cyclisation of ibogamine with a Heck reaction was possible.
Working on a model molecule, I found out that it should be possible and that it would be worth trying theses new developments on the natural product. But this reaction is hard to control, since it is a very special "coktail". It would need much more work to find out the good "receipt".
And why working on these Iboga structures ? It
was shown recently that molecule with the Iboga skeleton could
be used in the treatment of drug abuse and polydrug dependancy syndrome
. But neurotoxicity is a problem for some of these molecules. It
is why derivates have to be synthesized, in order to find the right
one, with the pharmacological activity but without the side effects.
18-methoxycoronaridine, synthesized recently, showed to be a potential
good candidate. Our research could help in this way, if we find out
a new shorter and "better" synthesis.