(−)-Dihydro-apovincaminic acid ethyl ester, preparation and use as a chiral modifier in enantioselective heterogeneous catalytic hydrogenations

✍ Scribed by A. Tungler; T. Máthé; T. Tarnai; K. Fodor; G. Tóth; J. Kajtár; I. Kolossváry; B. Herényi; R.A. Sheldon

• Book ID: 103977279
• Publisher: Elsevier Science
• Year: 1995
• Tongue: English
• Weight: 394 KB
• Volume: 6
• Category: Article
• ISSN: 0957-4166
• DOI: 10.1016/0957-4166(95)00317-i

✦ Synopsis

The preparation, characterisation and use of (-)-dihydro-apovincaminic acid ethyl ester as a chiral modifier in heterogeneous catalytic asymmetric hydrogenations is reported.

The epimeric compositions were determined using NMR and HPLC methods and circular dichroism spectroscopy was used to detect the interaction between the chiral modifier and the substrate.

Chiral modifiers for enantioselective heterogeneous catalytic hydrogenations can be classified into three main groups: alkaloids, ~-hydroxy acids and 0t-amino acids. The most well known examples are Ni catalysts modified with tartaric acid for the hydrogenation of 13-keto esters 1 and Pt catalysts modified with cinchona alkaloids for the hydrogenation of ¢t-keto esters 2. Both systems are effective (ee's up to 95%) in the hydrogenation of C=O double bonds in a specific class of substrates.

In an effort to find new chiral modifiers with different or broader substrate specifity we have screened several vinca and morphine-type alkaloids in the hydrogenation of various prochiral substrates 3. A vinca-type alkaloid, (-)-dihydro-apovincaminic acid ethyl ester [(-)-dihydro-vinpocetine, DHVIN, II] proved to be an effective chiral additive in the hydrogenation of both C=C and C=O double bonds. The unsaturated compound I, apovincaminic acid ethyl ester, (vinpocetine,VIN) is a synthetic drug which is used in the treatment of oxygen-deficiency of the brain 4. A patent 5 describes the preparation of the dihydro compounds 1I and 1II by the Pd black mediated hydrogenation of I. The two epimeric products II and HI were obtained in yields of 42% and 9% respectively, by crystallisation.

In the present study, the hydrogenation of I, the determination of its epimeric composition with NMR and I-IPLC methods, the separation and the molecular modelling of the epimers is described. The interaction of II