BE837049A

BE837049A - PROCESS FOR PREPARING NATURAL VINCAMINE FROM TABERSONIN

Info

Publication number: BE837049A
Application number: BE163085A
Authority: BE
Priority date: 1975-12-24
Filing date: 1975-12-24
Publication date: 1976-04-16

Description

       

  Procédé de préparation de la vincamine naturelle à partir de la tabersonine.

La présente invention qui est due à

  
Monsieur Jean Lévy, 18ter Rue Houzeau Muiren à Reims (France) se rapporte à un procédé de synthèse relatif à la préparation de la vincamine naturelle et constitue une amélioration  apportée au procédé selon le brevet belge No 761.628.

  
Conformément audit brevet belge, la tabersonine
(I) est transformée par hydrogénation catalytique en  vincadifformine (II) et celle-ci, traitée par 2 équivalents 

  
 <EMI ID=1.1>  hydroxy-oxyaspidospermidine qui par réduction et réarrangement donne la (-)vincamine, l'épi-16 vincamine et l'apo-

  
L'invention a pour but de conduire avec un bon rendement essentiellement à la vincamine et accessoirement à l'épi-16 vincamine en employant 1,1 équivalent de peroxyde au lieu de 2 équivalents.

  
Selon l'invention, la vincadifformine (II) est salif iée par un acide organique pour donner le sel correspondant (III) . Ce produit est alors traité par

  
1, équivalent de peroxyde pour donner le dérivé 16-hydroxy

  
 <EMI ID=2.1> 

  
donne la vincamine (v) et l'épi-16 vincamine (VI).

  
Le schéma de la réaction est le suivant : 

  

 <EMI ID=3.1> 




  Process for preparing natural vincamine from tabersonine.

The present invention which is due to

  
Mr. Jean Lévy, 18ter Rue Houzeau Muiren in Reims (France) relates to a synthetic process relating to the preparation of natural vincamine and constitutes an improvement made to the process according to Belgian patent No. 761,628.

  
In accordance with said Belgian patent, tabersonine
(I) is transformed by catalytic hydrogenation into vincadifformin (II) and this, treated with 2 equivalents

  
 <EMI ID = 1.1> hydroxy-oxyaspidospermidine which by reduction and rearrangement gives (-) vincamine, epi-16 vincamine and apo-

  
The object of the invention is to lead with a good yield essentially to vincamine and secondarily to epi-16 vincamine by using 1.1 equivalents of peroxide instead of 2 equivalents.

  
According to the invention, vincadifformin (II) is salified with an organic acid to give the corresponding salt (III). This product is then processed by

  
1, equivalent of peroxide to give the 16-hydroxy derivative

  
 <EMI ID = 2.1>

  
gives vincamine (v) and epi-16 vincamine (VI).

  
The reaction scheme is as follows:

  

 <EMI ID = 3.1>

Claims

acetic at 10% water. Leave in contact for 2 hours. The acetic solution is then made alkaline with caustic soda and extracted with three times 2 liters of chloride

methylene. Methylene chloride solutions washed with water, dried, distillate a residue

weighing 101.5 g (Yield 97%). By crystallization in acetone, 68 g of vincamine (V) and 15 g of epi-16 are obtained <EMI ID = 4.1>

reference tillons.

1. Process for preparing natural vincamine from tabersonine by semisynthesis, tabersonine being, in a first stage, converted by catalytic hydrogenation into vincadifformin, characterized in that vincadifformin of formula

is salified with an organic acid to give the corresponding salt of formula In detail, the various stages of the invention are achieved as follows:

tabersonine (I) is salified in a solvent not

organic acid such as acetic acid, trichloroacetic acid, trifluoroacetic acid, formic acid to give the corresponding salt (III). The organic solution is then treated with 1.1 equivalent of a peracid such as

performic acid, peracetic acid. It is left in contact overnight and evaporated to dryness. The residue (IV) is dissolved in a liquid organic acid of low molecular weight and preferably acetic acid at 10% water, the residue is left in contact for 2 hours. The acid phase is basified to pH 10 and extracted with an organic solvent such as methylene chloride, chloroform, ether or benzene. The organic phase is decanted, washed with pure water, dried over a dehydrating agent such as

sodium sulphate and finally deprived of solvent by distillation. The crude product is crystallized from acetone, methanol or ethanol to give vincamine (V) and epi-16 vincamine (VI) in respective proportions

65% and 15%.

The following example illustrates without limitation the characteristics of the invention:

Example

A solution of 100 g of vincadifformin

(II) in 2 liters of benzene is added 34 g of acid

We leave in contact overnight. The solution is then evaporated and the residue is dissolved in 1 liter of acid

� <EMI ID = 11.1>

where R-COO � denotes the residue of carboxylic acid,

valent peroxide to give the corresponding 16-hydroxy derivative of formula

by rearrangement

the formula vincamine <EMI ID = 16.1> and epi-16 vincamine of formula

2. Method according to claim 1, characterized in that the vincadifformin (II) is salified in an organic solvent immiscible with water such as benzene.

or toluene, with an organic acid such as acetic acid, trichloroacetic acid. trifluoroacetic acid, formic acid to give the corresponding salt (III).

3. Method according to claim 2, charac-

organic is treated with 1.1 equivalents of a peracid such as metachloroperbenzolque acid, paranitroperbenzolque acid, performic acid and peracetic acid.

4. Method according to claim 3, characterized in that the salt (III) is left overnight in contact with the peracid and the solution is evaporated to dryness.

5. Method according to claim 4, characterized in that the evaporation residue, consisting of the compound (IV) is dissolved in a liquid organic acid of low molecular weight.

6. Method according to claim 5, characterized in that the organic acid consists of acetic acid at 10% water. 7. Method according to any one of claims 5 and 6, characterized in that the compound (IV)

is left for 2 hours in contact with organic acid, the acid phase then being alkalinized to pH 10, extracted with an organic solvent such as methylene chloride) chloroform, ether or benzene, after what the organic phase is decanted, washed with water, dehydrated and deprived

being recrystallized to give wine amine (V) and epi-16 vincamine (VI).

8. Method according to claim 7, characterized in that the dehydrating agent is sodium sulfate.

9. Method according to claim 7, characterized in that the recrystallization solvent is chosen from acetone, methanol or ethanol.