Studies On The Synthesis Of Slective α_1A/D-AR Antagonist Tamsulosin

The efficacy of 1 - Adrenergic receptors(AR) antagonists on the lower urinary tract symptom(LUTS) in patients with benign prostatic hyperplasia(BPH) is widely accepted . Targeting of the 1A-AR with antagonists is important in relaxing prostate smooth muscle and relieving bladder outlet obstruction (BOO). Targeting of irritative symptoms, increasing evidence suggests that 1D-AR antagonist will be required. The new 1-AR antagonists tamsulosin is modestly selective for 1A-adrenoceptor and 1D-Adrenoceptor than for 1B-adrenoceptor, which is used only for BPH and dose not reduce blood pressure at the doses used to relax prostatic smooth muscle .In this paper, the synthetic methods of tamsulosin were discussed and a optimized 11- step synthetic route was chosen. The optically active R-(-)-5-(2-aminopropyl)-2-methoxy benzenesulfonamide (I)was prepared by two steps:1, condensation between R-(+)-a-methylbenzylamine and 5-acetonyl-2-methoxybenzenesulfonamide in the presence of reducing agent to obtain high optical purity lR,2R-2-methoxy-5-[2-(1-mthylbenzylamino)-propyl] -benzenesulfonamide (II). 2. Hydrogenesis of compound (II) to obtain compound (I).R-(-)-tamsulosin and its isomers were prepared. We have invented a new method for preparing S-(+)-tamsulosin and (?-tamsulosin. The process is capable of producing optically active R-(-)-tamsulosin of high optical purity (>99.8%) with higher reaction yield (4.5%).The structure of target molecule was determined by 13C-NMR, 1H-NMR , MS and IR. The optical purity was determined by high-performance capillary electrophoresis.