Syntheses of the (±)-, (+)-, and (−)-Forms of 2-Amino-3-(8-hydroxyquinolin-3-yl)propanoic Acid (8HQ-3Ala) from a Common Dehydroamino Acid Methyl Ester Precursor

The (±)-, (+)- and (−)-forms of 2-amino-3-(8-hydroxyquinolin-3-yl)-propanoic acid (1 or 8HQ-3Ala) have been prepared from o-methoxyacetanilide (2). A combination of Vilsmeier-Haack, Erlenmeyer-Plöchl and methanolysis reactions was used to convert compound 2 into the Z-configured dehydroamino acid derivative 5. Catalytic hydrogenation of the latter compound then gave, after reductive dechlorination and demethylation steps, compound (±)-1. Asymmetric hydrogenation of compound 5 using a rhodium precatalyst and an enantiopure DuPhos-type ligand selectively delivered either acid (+)-1 or (−)-1. The structure, including absolute configuration, of the latter product was confirmed through single-crystal X-ray analysis of the corresponding HBr mono salt.