Preparation of both enantiomers of β2-(3,4-dihydroxybenzyl)-β-alanine, higher homologues of Dopa

Abstract β 2 -(3,4-Dihydroxybenzyl)-β-alanine [β 2 -Homo-Dopa, 1 ] is a novel β-amino acid homologue of Dopa, the most successful therapeutic agent in the treatment of Parkinson's disease. Enantioenriched ( R )- 1 and ( S )- 1 were obtained via the diastereoselective alkylation of enantiopure pyrimidinone ( R )- and ( S )- 3 , chiral derivatives of β-alanine, with veratryl iodide. The major diastereomeric products (2 S ,5 R )- 4 and (2 R ,5 S )- 4 were hydrolyzed with 57% HBr, and the desired β-amino acids were purified by silica gel chromatography. Alternatively, enantioenriched ( R )- and ( S )- 1 were prepared by means of the highly diastereoselective alkylation (3,4-dimethoxybenzyl iodide) of open-chain β-aminopropionic acid derivatives ( R , R , S )- 8 and ( S , S , R )- 8 containing the chiral auxiliary α-phenylethylamine. Finally, nearly enantiopure ( R )- and ( S )- 1 were obtained by resolution of racemic N -benzyloxycarbonyl-2-(3,4-dibenzyloxybenzyl)-3-aminopropionic acid, rac - 12 , with ( R )- or ( S )-α-phenylethylamine, followed by catalytic hydrogenolysis.