Amino Acids and Peptides. XXIII. An Asymmetric Synthesis of (R)-(-)-Laudanosine from L-3-(3, 4-Dihydroxyphenyl) alanine

Abstract

Following the previous asymmetric syntheses of (S)-(+)-laudanosine (V) and (S)-(+)-reticuline (VI) from L-3-(3, 4-dihydroxyphenyl) alanine (L-DOPA), (R)-(-)-laudanosine (XXIV) has been also synthesized from L-DOPA. A key step is an epimerization of (1S, 3S)-methyl 1-(3, 4-dimethoxybenzyl)-6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylate (XIa), which was derived from a major product of the Pictet-Spengler reaction of the methyl ester of L-DOPA (Ia) and sodium 3-(3, 4-dimethoxyphenyl) glycidate (IIa), to (1R, 3S)-isomer (XIIa) under the hydrogenation condition using PtO₂ in MeOH-AcOH (100 : 1). XIa and XIIa are interconvertible under this condition. Isomerization reactions of XIa and XIIa in a basic medium (MeONa in MeOH) have been also examined. Both compounds epimerize at C-3 position and afford the new (1S, 3R)-(XIII)-and (1S, 3R)-(XIV)-isomers, respectively.