| SYNTHESIS |
"Development of a Practical Synthesis of Sumanirole" . Author presented the development of the process synthesis of Sumanirole, a clinical candidate for treatment of Parkinson’s Disease (Scheme 8). He began by describing the early route used to supply initial clinical material (Scheme 9) and the problems associated with this route. One main problem was that the synthesis started with the non-natural enantiomer of the amino acid. They wanted to develop a synthesis that began with a less expensive and more readily available starting material and settled on a quinoline derivative (Scheme 10). From there they would build the third ring and add the needed functionality and chirality to the qunioline ring system. The first challenge was met without many problems but addition of the amino functionality to the quinoline system proved more difficult. After investigating many routes (including Evans and Jacobsen aziridation, Sharpless aminohydroxylation, fermentation to give a chiral epoxide, and other chiral epoxide formations) it was found that the most efficient route was to make a racemic hydroxybromide intermediate and resolve it by reaction with (R)-naproxen. Scheme 11 shows the route used in the synthesis of large quantities needed for clinical evaluation |
| UPDATE | 03.03 |
| AUTHOR | This data is not available for free |
| LITERATURE REF. | This data is not available for free |
|
Want more information ? Interested in the hidden information ? Click here and do your request. |