ENANTIOSELECTIVE SYNTHESIS OF S-1452, AN ORALLY ACTIVE POTENT THROMBOXANE-A2 RECEPTOR ANTAGONIST

An efficient and extremely practical enantioselective fission of pro-chiral bicyclo[2.2.1]heptane-2,3-dicarboxylic anhydride was applied to the asymmetric synthesis of the potent and orally active thromboxane A2 (TXA2) receptor antagonist, S-1452. The lithium salt of (R)-(-)-benzylmandelate was employed as a chiral ligand, giving a crystalline key intermediate 3 of which the chemical purity was 100.0% after crystallization. Epimerization and the methanolysis process of 3 afforded the half ester 4, which was transformed into S-1452.