Threo-adrenalinecarboxylic acid, and the production and uses thereof

Abstract

DL- or L-Threo-3-(3,4-dihydroxyphenyl)-N-methyl-serine which may also be termed as DL- or L-threo-adrenalinecarboxylic acid are now provided, which are new compounds useful for therapeutic treatment of Parkinson's disease and mental depression disease. DL-Adrenalinecarboxylic acid may be produced by a new process comprising reacting glycine with O-protected 3,4-dihydroxybenzaldehyde, hydrolyzing the resultant reaction product under acidic conditions to form O-protected DL-3-(3,4-dihydroxyphenyl)serine, isolating the O-protected DL-3-(3,4-dihydroxyphenyl)serine into the threo isomer and the erythro isomer by recrystallization from a suitable organic solvent, introducing an unsubstituted or substituted benzyl group into the 2-amino group of the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine, then N-methylating the resulting O-protected DL-threo-3-(3,4-dihydroxyphenyl )-N-benzylserine, and removing the O-protecting groups as well as the unsubstituted or substituted benzyl group at the 2-methylamino group of the N-methylation product. L-Adrenalinecarboxylic acid may be produced by a new process comprising introducing a p-methoxybenzyloxycarbonyl group into the 2-amino group of the O-protected DL-threo-3-(3,4-dihydroxyphenyl)serine obtained as an intermediate product, optically resolving the resultant O-protected DL-threo-3-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine by reacting the latter with an optically active amine and recrystallizing the resultant amine salt products from a suitable organic solvent, removing the p-methoxy-benzyloxycarbonyl group from the resultant O-protected L-threo-(3,4-dihydroxyphenyl)-N-p-methoxybenzyloxycarbonyl-serine, reacting the resultant O-protected L-threo-(3,4-dihydroxyphenyl)serine with dimethyl sulfate in dry acetone to form an O-protected L- or D-threo-(3,4-dihydroxyphenyl)-N-methylserine methyl ester, saponifying this methyl ester and then removing the O-protecting groups from the saponification product.