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La
période neuchâteloise
(I)(II)

Some information about my Diploma Work, done in the lab of Prof. R. Neier, from January 2000 to September 2000.  

 
Tabernanthe iboga
is a psychoactive plant from Central Africa, used in traditional rituals [1]. From its roots was isolated in 1901 ibogamine, one of the alkaloids responsible for its psychoactive properties [2]. The C20H26N2O formula was established in 1944, its structure elucided in 1957 and confirmed by X-ray analysis in 1960 [3,4].

 

Tabernanthe iboga
(unknown source)

 

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 [7]. They contain a closely related to the Iboga type part.
 

Vinblastine (R = CH3) and vincristine (R = CHO), two alkaloids with
a slightly modified Iboga part, used in the treatment of cancers.

 

Since the first total synthesis of (▒)-ibogamine, made by Büchi et al. in 1965 [8], 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 [1]. 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.

 

18-methoxycoronaridine

 

[1]
P. Popik, R. T. Layer, P. Skolnick, Pharmacological Reviews 1995, 47, 235.
[2]
E. Schlitter, C. A. Burkhardt, E. Gellert, Helv. Chim. Acta 1953, 36, 1337.
[3]
W. I. Taylor, J. Am. Chem. Soc. 1957, 79, 3298.
[4]
G. Arai, J. Coppola, G. A. Jeffrey, Acta Cryst. 1960, 13, 553.
[5]
C. Frauenfelder, H.-J. Borschberg, Helv. Chim. Acta 2000, 83, 1753.
[6]
H. Takayama, S. Suda, I.-S. Chen, M. Kitajima, N. Aimi, S.-I. Sakai, Chem. Pharm. Bull. 1994, 42, 280.
[7]
K. Hostettmann, O. Potterat, J.-L. Wolfender, Chimia 1998, 52, 10.
[8]
G. Büchi, D. L. Coffen, K. Kocsis, P. E. Sonnet, F. E. Ziegler, J. Am. Chem. Soc.1965, 87, 2073.
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- Update : December 2001 -
Stage Max-Delbrück Centrum (Berlin)
Concours " La science appelle les jeunes "
Curriculum vitae
___________________________
la période genevoise (UniGE)
Symposium de Zermatt (CREANDO)
Stages Hoffmann-La Roche 1999 / 2001 (Bâle)