DEVELOPING AN OXAZOLIDINE-2-THIONE BASED APPROACH TO THE ASYMMETRIC SYNTHESIS OF BACLOFEN, AN AGENT IN THE TREATMENT OF SPASTIC MOVEMENT DISORDERS INCLUDING CEREBRAL PALSY AND MULTIPLE SCLEROSIS
Baclofen belongs to a class of medicinal agents that are structurally related as gamma-amino acids. We seek to prepare baclofen through a chiral auxiliary mediated pathway. The synthetic pathway that will be discussed on the poster includes preparation of the oxazolidine-2-thione from the commercially available L-phenylglycinol with carbon disulfide, and acylation of the thione via the Steglich reaction with bromoacetic acid and chloroacetic acid. The use of bromoacetic acid proved to be problematic due to the age and quality of the reagent. The acylation of the thione with the chloroacetic acid was more straightforward and the product could be obtained more readily via flash chromatography. Research is underway to apply this substrate in a nucleophilic substitution reaction with the lithium hexamethyldisilazane (LiHMDS) derived carbanion of benzyl nitrile. The success of the alkylation will be gauged by the level of diastereoselection observed in the 500 MHz proton NMR spectra. Hydrolysis of the addition product under catalytic imidazole conditions in an aqueous environment will generate a beta-cyano carboxylic acid that will be selectively reduced to the desired gamma-amino carboxylic acid, baclofen.
Wendorf, Micah, "DEVELOPING AN OXAZOLIDINE-2-THIONE BASED APPROACH TO THE ASYMMETRIC SYNTHESIS OF BACLOFEN, AN AGENT IN THE TREATMENT OF SPASTIC MOVEMENT DISORDERS INCLUDING CEREBRAL PALSY AND MULTIPLE SCLEROSIS" (2019). University Research Symposium. 300.