Study On Synthesis Of Antiparkinsonian Drug SK&F101468A

Parkinson's disease(PD), namely paralysis agitans, is a vulgar nervous systemdisease. Trembor, rigidity, myasthenia and hypokinesea are the common presentingsymptoms.Drugs in common use include: like-dopamine agents, anti-cholinerigic agents, DAreceptor agonists, COMT inhibitor and MAO-B inhibitor etc. Now at home only afew of drugs are used for PD therapy, such as L-dopa, carbedopa, bromocriptine,amantadine etc, but the effects of these drugs are poor, so we need drugs with bettereffects and neuroprotective action.SK&F101468-A was developed by British Smithkine Beecham PharmaceuticalCompany. SK&F101468-A was on market in September 1996 at England,brandname was Requip, it could be bought in Canada, France, Switzerland and Germanyand was approved in all the markets expect to Japan. In 1998 FDA approved thatSK&F101468-A was used for therapy of PD's primary symptoms and late patients withPD as L-dopa assistant drug.Select two routes to synthesize SK&F101468A successfully. In the first route, itwas synthesized by cyclization reaction, bromination, condensation, Royer reaction,reduction, nucleophilic substitution (total six steps) starting fromβ-phenyl ethanol in5% total yields. In the second route similarly it was synthesized by cyclizationreaction, benzoylization, condensation, Royer reaction, reduction, hydrolysis,tosylation, nucleophilic substitution (total nine steps) starting fromβ-phenyl ethanolin 9% total yields, furthermore research the technics of intermediates ofSK&F101468-A.The structures of the key intermediates and the target product were confirmed bythe analysis of ~1H-NMR data.