Potential GABA_B Receptor Antagonists. VI. The Synthesis of Saclofen and Other Sulfonic Acid Derivatives

Abstract

Saclofen, 3-amino-2-(4chlorophenyl) propanesulfonic acid (3), has been synthesized by two routes. Attempts to hydrogenolyse or dehydrate the 2-hydroxy derivative were unsuccessful, however. Radical sulfonation of 3-amino-1-bromo-2-(4-chlorophenyl) propene gave 3-amino-2- (4-chlorophenyl)propene-1-sulfonic acid (6) which was readily reduced to (3). Alternatively, 2-(4-chlorophenyl)-3-phthalimidopropene underwent radical addition of thioacetic acid, and oxidation of the product to the sulfonyl chloride and hydrolysis gave (3). The corresponding sulfonamide (4) was also prepared. The acid (3) is a powerful specific antagonist of GABA at the GABA_B receptor, while (4) and (6) are only weak antagonists.